Patent Application 16098145 - IMPROVED DRUG FORMULATIONS

Title: IMPROVED DRUG FORMULATIONS

Application Information

Invention Title: IMPROVED DRUG FORMULATIONS
Application Number: 16098145
Submission Date: 2025-04-10T00:00:00.000Z
Effective Filing Date: 2018-11-01T00:00:00.000Z
Filing Date: 2018-11-01T00:00:00.000Z
National Class: 424
National Sub-Class: 465000
Examiner Employee Number: 86829
Art Unit: 1615
Tech Center: 1600

Rejection Summary

102 Rejections: 0
103 Rejections: 3

Cited Patents

No patents were cited in this rejection.

Office Action Text

DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.

Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 10/25/2024 has been entered.

Information Disclosure Statement
The information disclosure statement (IDS) submitted on 10/25/0224 has been considered by the examiner.

Status of the Claims
The response filed 10/25/2024 is acknowledged.
Claims 1-3, 5-16, 20-23, 26-29, 31, 35-37, 41-42, 44 and 46-54 are pending.
Claims 1-3, 5-16, 20, and 47-53 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 09/29/2020.
Claims 21-23, 26-29, 31, 35-37, 41-42, 44, 46 and 54 are treated on the merits in this action.
The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application. Rejections not reiterated herein have been withdrawn.

Response to Arguments
Applicant's arguments filed 10/25/2024 have been fully considered but they are not persuasive.

With respect to the rejection of claims 21, 22, 23, 26-29, 31, 35, 36, 37, 41, 42, 44, 45, 46, and 54 under 35 U.S.C. 103 as being unpatentable over Cao, J. Kor. Pharm. Sci., 33, 1, 2003 in view of Brough, US 20090053315 and CN 104434809 A (Zou).
1. Cao, Brough, and Zou
Applicant argues A. Cao does not disclose, teach, or suggest “wherein the non-polymeric lubricant is an agent selected from the group consisting of magnesium stearate and sodium stearyl fumarate” as recited in claim 21.
The examiner agrees. However, both Brough and Zou clearly teach incorporating lubricants such as magnesium stearate and sodium stearyl fumarate in solid dispersions like those of Cao. See citations below, e.g., Zou, e.g., claims 1 and 2. Zou teaches the addition of lubricant to the API polymer dispersion results in an amorphous dispersion which is as stable or more stable than an amorphous dispersion which contains only the API and the polymer (Zou, e.g., pg. 2/5, Invention Content, ¶ 2). Lubricants include magnesium stearate, sodium stearyl fumarate, and sodium lauryl sulfate (Zou, e.g., pg. 2, Invention Content).

Applicant argues B. Skilled persons would not have been motivated to substitute the soluble agents of Cao with insoluble or poorly soluble non-polymeric lubricants such as sodium stearyl fumarate or magnesium stearate to enhance dissolution of poorly soluble active ingredients.
This argument is unpersuasive at least because the rejection does not rely on substituting soluble agents with insoluble agents. As clearly set forth in the rejection below and the previous final rejection of record: It would have been obvious before the effective filing date of the presently claimed invention to modify a single phase solid amorphous dispersion comprising an API, one or more pharmaceutically acceptable excipients (PVP), and a lubricant, e.g., sodium lauryl sulfate, as known from Cao and Brough by including magnesium stearate and/or sodium stearyl fumarate in the single phase solid amorphous dispersion as suggested by Zou using techniques for preparing single phase solid dispersions known in the art from Brough with a reasonable expectation of success. The skilled artisan would have been motivated to make this modification to improve the stability of the amorphous API in the composition during storage in the same way suggested by Zou with a reasonable expectation of success. The skilled artisan would have had a reasonable expectation of success because Cao teaches compositions comprising combinations of excipients including polymers and lubricants such as sodium lauryl sulfate, because Brough suggests a variety of pharmaceutical excipients are useful for preparing amorphous dispersions including stearates and magnesium stearate, and because Zou suggests lubricants including magnesium stearate, and sodium stearyl fumarate were known and used for the purpose of improving the stability of the amorphous character of poorly water-soluble drugs in similar amorphous dispersion pharmaceutical compositions.
To the extent that Applicant argues it was counter intuitive to incorporate insoluble or poorly soluble non-polymeric lubricant in the amorphous solid dispersion of a formulated API, it is noted that Zou teaches the addition of lubricant to the API polymer dispersion results in an amorphous dispersion which is as stable or more stable than an amorphous dispersion which contains only the API and the polymer (Zou, e.g., pg. 2/5, Invention Content, ¶ 2). Lubricants include magnesium stearate, sodium stearyl fumarate, and sodium lauryl sulfate (Zou, e.g., pg. 2, Invention Content).
It is also noted that Brough amorphous dispersion composites may include magnesium stearate (Brough, e.g., 0018). It is also noted that Lundbeck teaches amorphous dispersions containing sodium stearyl fumarate, e.g., Lundbeck’s dispersions also contain sodium stearyl fumarate which is a lubricant named in claim 45 (Lundbeck, e.g., Table 1). Each of Brough, Zou, and Lundbeck, independently, clearly disclose adding magnesium stearate or sodium stearyl fumarate to an amorphous dispersion for improved drug dissolution.
The reference “Ansel’s” has been given full consideration. However, Ansel’s relates to the use of magnesium stearate as a lubricant.
The reference “Louw” has been given full consideration. However, Louw relates to the use of magnesium stearate as a lubricant, specifically a lubricant coating (Louw, pg. 5 cited in the remarks, 10/25/2024, pg. 6).
Neither Ansel’s, nor Louw appear to directly comment on the use of magnesium stearate as an additive in a single-phase amorphous solid dispersion, or a single-phase solid solution.
The term “lubricant” is a functional term which has a specific meaning in the galenic pharmaceutical arts. See, e.g., Chal, US 20170360874 A1 (of record), e.g., 0092:
The term “lubricant” refers to a substance added to a powder blend to prevent the compacted powder mass from sticking to the equipment during the tableting or encapsulation process. A lubricant can aid the ejection of the tablet form the dies, and can improve powder flow. Non-limiting examples of lubricants include magnesium stearate, stearic acid, silica, fats, calcium stearate, polyethylene glycol, sodium stearyl fumarate, or talc; and solubilizers such as fatty acids including lauric acid, oleic acid, and C.sub.8/C.sub.10 fatty acid.
In contrast to this definition, the presently claimed invention, Zou, Lundbeck, and Brough use the term “lubricant” to refer to a genus of excipient additives which are incorporated into a single-phase solid amorphous dispersion or a single-phase solid solution.
Since Zou, Lundbeck, Brough, and the claimed invention uses magnesium stearate as an additive in a solid dispersion, the relevance of Ansel’s and Louw to the current inquiry is not clear. Both Ansel’s and Louw refer to the use of magnesium stearate as a “lubricant” as would be understood according to Chal.
Moreover, despite the teachings of Ansel’s and Louw, it is noted that Cao, Zou, Lundbeck, and Brough all teach the use of lubricants in a solid dispersion with improved dissolution properties, e.g., offered by stabilizing the amorphous form of poorly water-soluble drugs.
Zou, like the claimed invention, uses the term lubricant, e.g., magnesium stearate (Zou, e.g., claims 1-2) and sodium stearyl fumarate (Zou, e.g., pg. 3) as an additive in the solid dispersion:

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Zou clearly teaches incorporating at least a portion of the lubricant into the solid dispersion (drug, povidone, and part of the lubricant agent are mixed to prepare the solid dispersion). Further, Zou uses magnesium stearate as a lubricant in the granules (rest of lubricant is added and mixed after extrusion and compressed to obtain a tablet).
Further still, as seen in Zou, pg. 3, supra, there is a suggestion to use sodium lauryl sulfate and magnesium stearate in combination.

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Like Zou, Brough clearly suggests magnesium stearate may be used as an excipient in a nanocomposite (Brough, e.g., 0018), and more generally teaches stearates may be used to form a composite with poorly soluble APIs (Brough, e.g., 0013), which composites exhibit enhanced dissolution of a so formulated poorly water-soluble drug (Brough, e.g., 0085).
Thus, the cited prior art suggests magnesium stearate may be used as an additive in solid dispersions for enhanced dissolution formulations of poorly water-soluble drugs. The teachings of the cited prior art would have prompted the skilled artisan to modify Cao’s single-phase dispersions with magnesium stearate to prevent crystallization of the drug in the dispersion as suggested by Zou with a reasonable expectation of success.
Even if magnesium stearate was known to retard release of the drug, the teachings of Zou suggest the reduction of drug release contributed by magnesium stearate is worth the dissolution gained from preserving the stability of the amorphous nature of the drug in the composition. This would particularly be true in the case where the amorphous form of the drug is a single-phase solid solution. Given the effort required to prepare an amorphous solid dispersion including solid solutions for increased drug dissolution as reported in Brough, the skilled artisan would have used Zou’s technique of adding lubricants such as magnesium stearate to the amorphous dispersion to preserve the amorphous nature of the drug.

Applicant argues C. Cao provides no evidence that the solid dispersions of Cao prepared using solubilizers (oleic acid, sodium lauryl sulfate, and/or TWEEN 80), are "[a] pharmaceutical composition comprising a single-phase solid amorphous dispersion of (a) an active pharmaceutical ingredient, (b) one or more pharmaceutically acceptable excipients, and (c) a non-polymeric lubricant...," as recited in pending independent claim 21.

Applicant argues the rejection relies on the assertion that each of the composition in Cao are pharmaceutical compositions comprising a single phase solid amorphous dispersion of (a) an active pharmaceutical ingredient, (b) one or more pharmaceutically acceptable excipients, and (c) a non-polymeric lubricant. However, Chal, US 20170360874 in support of the assertion that “the solubilizers in Cao are lubricants” is no longer cited.
This argument is not persuasive because at least sodium lauryl sulfate is recognized in Zou as a lubricant. This was pointed out in the previous Office action: Cao does not use the term “lubricant” in reference to oleic acid, TWEEN 80 and sodium lauryl sulfate. However, “lubricant” is a functional term referencing the property of compounds, i.e., compounds which exhibit the property of lubricity. Further at least sodium lauryl sulphate was an art recognized lubricant before the effective filing date of the presently claimed invention as evident from Zou. Consequently, Cao as evidenced by Brough and Cao in view of Brough teaches a single phase, solid amorphous dispersion comprising an API, an excipient (polymer), and a lubricant (sodium lauryl sulfate) as evidenced by Zou, e.g., claim 1.

Applicant argues the rejection relies on the assertion that each of the composition in Cao are pharmaceutical compositions comprising a single phase solid amorphous dispersion of (a) an active pharmaceutical ingredient, (b) one or more pharmaceutically acceptable excipients, and (c) a non-polymeric lubricant. However, the rejection concedes that Cao shows no Ex-ray diffractogram or DSC thermogram evidence to support the assertion that Cao’s compositions F2-F11 are single-phase solid dispersions of LOS, PVP a non-polymeric lubricant. Applicant argues that in the absence of any evidence the Action simply assumes that F2-F11 are single phase solid dispersions merely on the basis that Cao refers to F1 and F2-F11 as solid dispersions.
This argument is unpersuasive.
Cao teaches a solid dispersion comprising a pharmaceutically active agent (API), an excipient, e.g., polyvinylpyrrolidone (PVP), and an additional excipient, i.e., oleic acid (OA), tween 80 (TW 80) and/or sodium lauryl sulfate (SA). See Cao, entire document, e.g., Abstract and pg. 8, Table 1. Oleic acid, TWEEN 80 and sodium lauryl sulfate are exemplified in combination with API and PVP both individually or in combination (Cao, e.g., pg. 8, table 1).
Cao very clearly teaches solid dispersions including a drug (LOS), PVP (pharmaceutical excipient), and Oleic acid, TWEEN 80 and sodium lauryl sulfate which are named embodiments in combination with API and PVP both individually or in combination (Cao, e.g., pg. 8, table 1, and Preparation of solid dispersion: A solid dispersion containing LOS was prepared using PVP as a water-soluble substrate and using soluble agents such as SLS. TW 80 and OA alone or in combination.)
As seen in Fig. 5, an amorphous solid dispersion according to Cao is a single phase. Cao does not characterize the x-ray diffractograms or DSC of any of formulations F2-F11. However, since Cao calls formulations F2-F11 “solid dispersions” like F1, these lubricant containing formulations (F2-F11) are expected to have the same properties, including similar x-ray diffractograms and DSC as those characterized for F1.
Applicant has shown no evidence to the contrary.
“As a practical matter, the Patent Office is not equipped to manufacture products by the myriad of processes put before it and then obtain prior art products and make physical comparisons therewith.” MPEP 2113 It is noted that In re Best (195 USPQ 430) and In re Fitzgerald (205 USPQ 594) discuss the support of rejections wherein the prior art discloses subject matter which there is reason to believe inherently includes functions that are newly cited or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to "prove that subject matter shown to be in the prior art does not possess characteristic relied on" (205 USPQ 594, second column, first full paragraph).
Here, the solid amorphous dispersion composition of both the claims and the cited prior art contains an active pharmaceutical agent, a pharmaceutical excipient, and a lubricant. Further, the prior art composition appears to be a single phase, amorphous solid dispersion based on the data presented in Cao at Figs. 4 (X-ray diffraction) and 5 (DSC thermogram). Cao offers no reason, like separate terminology, to believe the lubricant containing compositions (F2-F11) exhibit X-ray diffraction or DSC thermograms different from those shown for F1. Further, Cao’s lubricant containing solid dispersions (F2-F11) show enhanced dissolution profiles, which are even superior to the single-phase amorphous solid dispersion formulation F1 (Cao, e.g., Fig. 7). These findings support the conclusion that the DSC and X-ray diffraction patterns of formulations F2-F11, which contain lubricant in the solid amorphous dispersion referenced by the previous office action, are solid dispersions having the recited properties of being a single phase and amorphous as claimed.
Furthermore, the present specification indicates the single phase solid amorphous dispersions may be prepared by solvent evaporation (Specification, e.g., pg. 3:1-14; pg. 7:16-25; and ¶ spanning pp. 8-9). Cao teaches preparing the solid amorphous dispersion comprising drug, polymer, and lubricant using solvent evaporation (Cao, e.g., pg. 8, c2: PREPARATION OF SOLID DISPERSION). The prior art composition is made in the same way proposed by the present specification and appears to be a single phase based on DSC as evident from Cao, e.g., pg. 12, fig. 5.

Applicant argues D. Brough does not remedy the deficiencies of Cao.
Applicant argues the Office acknowledges that Cao does not teach non-polymeric lubricants in a single phase solid amorphous dispersion recited in claim 21 as amended. Applicant argues the Office relies on the teachings of Brough and Zou to remedy the deficiencies of Cao. Applicant argues Brough does not teach a pharmaceutical composition comprising a single phase solid amorphous dispersion of an active pharmaceutical ingredient, one or more pharmaceutically acceptable excipients, and a nonpolymeric lubricant, let alone wherein the non-polymeric lubricant is magnesium stearate or sodium stearyl fumarate.
This argument is not persuasive. It is acknowledged Cao does not expressly teach magnesium stearate or sodium stearyl fumarate in the solid dispersions. Brough was not cited for teaching a single phase solid amorphous dispersion of an active pharmaceutical ingredient, one or more pharmaceutically acceptable excipients, and a nonpolymeric lubricant, let alone wherein the non-polymeric lubricant is magnesium stearate or sodium stearyl fumarate since that would be an anticipatory reference. Brough was cited to evidence that fact that the compositions of Cao which exhibit a single Tg are single phase solid dispersions. See Final rejection, pg. 13: Brough teach compositions exhibiting a single glass transition phase are single phase compositions (Brough, e.g., 0153). Cao, e.g., pg. 12, Fig. 5, shows solid amorphous dispersions exhibiting a single glass transition phase. Thus, Cao appears to teach a single phase solid amorphous dispersion as claimed as evidenced by Brough.
Brough was also cited for providing an express teaching to formulate Cao’s composition as a single phase in the event Applicant presents evidence that Cao’s formulations are not single-phase compositions. No evidence has been provided showing Cao’s formulations are not single phase solid amorphous dispersions as claimed.
Applicant’s arguments regarding Brough’s teachings of thermal lubricants as processing agents have been considered but are unpersuasive. Brough very clearly, and expressly states, lubricants may be used in the production of solid dispersions (Brough, e.g., 0114 and claim 7). It is acknowledged that Brough teaches processing agents, including plasticizers are optional (Brough, e.g., 0011 processing may be conducted with or without a processing agent and 0025). Brough’s disclosure that plasticizers and/or thermal lubricants are not required to achieve an amorphous dispersion does not teach away from the use of plasticizers and/or thermal lubricants in amorphous dispersions. See MPEP 2143.01, I. This is particularly true here, where Brough very clearly, and expressly states, lubricants may be used in the production of solid dispersions and where Cao clearly teaches the technique of including excipients known to those skilled in the art as lubricants, e.g., sodium lauryl sulfate, in the solid amorphous dispersion improving dissolution and increasing bioavailability of various poorly soluble drugs (Cao, e.g., pg. 13).
Moreover, claim 21 requires magnesium stearate or sodium stearyl fumarate. Applicant has not pointed out, and the Examiner is unable to find, any teaching in Brough which would have led the skilled artisan to conclude that the inclusion of magnesium stearate would change the principle of operation in Brough. To the extent that Brough relates to magnesium stearate or sodium stearyl fumarate, it is noted that Brough clearly teaches stearates, e.g., magnesium stearate, may be incorporated into solid dispersion composites as an excipient (Brough, e.g., 0013, 0018, claim 14).
It is noted that the combined teachings of Cao, Brough, and Zou teach solid amorphous dispersions which include an API, excipients including polyvinylpyrrolidone, and magnesium stearate as required by claim 21.
In response to Applicant’s argument that Brough does not suggest the successful formation of a single phase solid amorphous dispersion: It is noted that Brough teaches techniques which enable the production of a single phase, miscible composite of two or more pharmaceutical materials previously considered to be immiscible for utilization in a secondary processing step (Brough, e.g., 0100). Known techniques enable the formation of a single-phase composite with a variety of known pharmaceutical excipients including stearates (including magnesium stearate) and polymeric materials (Brough, e.g., 0013 and 0118). Brough teaches known techniques for preparing solid dispersions and single-phase materials include melt extrusion and thermokinetic compounding (Brough, e.g., 0107). Brough teaches single phase composites can be obtained using hot melt extrusion or thermokinetic processing as evidenced by a single Tg (Brough, e.g., 0153 and 0179-0180). Single glass transition is also indicative of amorphous solid solutions (single phase amorphous solid dispersions). See Brough, e.g., 0173. The skilled artisan would have recognized that Brough teaches techniques which enable the formulation of single phase solid amorphous dispersion composites comprising a drug and multiple excipients including polymers and stearates.

Applicant argues E. Zou does not remedy the deficiencies of Cao.
Applicant has argued there is nothing in the cited passage on Zou, pg. 2 in the remarks which suggests lubricants of Zou are part of an amorphous solid dispersion, arranged in the same way as required by claims 21. Applicant also points to Embodiment 6 in Zou wherein Zou teaches adding magnesium stearate and sodium lauryl sulfate after the formation of the solid dispersion.
This argument is unpersuasive.
The teachings of Zou are not limited to the sections cited by Applicant. Zou very clearly teaches solid dispersions comprising a lubricant (Zou, e.g., claim 1). In fact, Zou very clearly teaches adding lubricants during the production of the solid dispersion (Zou, e.g., claim 2). It is noted that Zou teaches two alternatives for preparing a solid dispersion as seen from Zou, claim 2:

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In the first preparation, part of the lubricant is clearly added to the solid dispersion and the remainder of the lubricant is added after the solid dispersion is formed. In the alternative preparation, the lubricant is added after the formation of the solid dispersion. Applicant’s arguments focus on the second embodiment, while the Office action relies on the first embodiment. Zou exemplifies the addition of lubricant to the solid dispersion. See Zou, e.g., pg. 5, embodiment 5:

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Zou expressly teaches the lubricant magnesium stearate may be used with the lubricant silica, or as an alternative to the lubricant silica, or as an alternative to the lubricant sodium lauryl sulfate as employed by Cao, or in combination with the lubricant sodium lauryl sulfate as employed by Cao. See Zou, e.g., claim 1:

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Additionally, Zou expressly teaches the lubricant sodium stearyl fumarate may be used as an alternative to the lubricant magnesium stearate. See Zou, e.g., pg. 2:

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In light of Zou, claims 1-2, embodiment 5, and the sections of pg. 2 reproduced above, it is clear that adding a lubricant such as magnesium stearate to the solid amorphous dispersions of Cao would not change the principle of operation of Zou or Cao.
Therefore, the skilled artisan would have had motivation to add a lubricant such as magnesium stearate to Cao’s single phase solid dispersions for the improved stability reported in Zou with a reasonable expectation of success.

Regarding the rejection of claims 21, 22, 23, 26-29, 31, 35, 36, 37, 41, 42, 44, 45, 46, and 54 under 35 U.S.C. 103 as being unpatentable over WO 2015175505 (Lundbeck) in view of Brough, US 20090053315:
2. Lundbeck and Brough
Applicant respectfully disagrees with the rejection, at least for the reasons discussed below, as well as in Applicant's previous responses filed February 13, 2023, and September 25, 2023, and as discussed in Declarations by Robert O. Williams III, Ph.D., filed April 20, 2023, and September 25, 2023.
This argument has been considered but is unpersuasive at least because the referenced responses and declarations do not address the most recent rejections.
Applicant argues A. Brough fails to cure the deficiency of Lundbeck
Applicant argues there is nothing in the disclosure of Brough to suggest the successful formation of "...a single-phase solid amorphous dispersion of (a) an active pharmaceutical ingredient, (b) one or more pharmaceutically acceptable excipients, and (c) a non-polymeric lubricant...," as recited in amended claim 21. To the extent lubricants are used in Brough, the lubricants are referred to as "processing agents." There is no disclosure, teaching, or suggestion in Brough of the successful formation of a single-phase solid amorphous dispersion of an API, an excipient, and a lubricant, wherein all three of these components form a single-phase solid amorphous dispersion.
These arguments are unpersuasive for the reasons set forth above with respect to Brough in the previous rejection.

Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102 of this title, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.

This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.

Claims 21, 22, 23, 26-29, 31, 35, 36, 37, 41, 42, 44, 46, and 54 are rejected under 35 U.S.C. 103 as being unpatentable over Cao, J. Kor. Pharm. Sci., 33, 1, 2003 in view of Brough, US 20090053315 and CN 104434809 A (Zou).
Applicable to claim 21:
Cao teaches a solid dispersion comprising a pharmaceutically active agent (API), an excipient, e.g., polyvinylpyrrolidone (PVP), and an additional excipient, i.e., oleic acid (OA), tween 80 (TW 80) and/or sodium lauryl sulfate (SA). See Cao, entire document, e.g., Abstract and pg. 8, Table 1. Oleic acid, TWEEN 80 and sodium lauryl sulfate are exemplified in combination with API and PVP both individually or in combination (Cao, e.g., pg. 8, table 1).
Solid dispersions are prepared by fully dissolving the API, PVP and solubilizer (Cao, e.g., pg. 8, c2: PREPARATION OF SOLID DISPERSION).
Cao teaches the API and the entire composition is amorphous (Cao, e.g., pg. 11, Fig. 4). Solid dispersions appear to be amorphous by x-ray diffraction (Cao, e.g., pg. 11, Fig. 4). Thus, Cao teaches a solid amorphous dispersion of an active pharmaceutical ingredient, pharmaceutically acceptable excipient (PVP), and oleic acid, sodium lauryl sulfate, and/or TWEEN 80.
Cao teaches single phase solid amorphous dispersions. Cao’s solid dispersions appear to be a single phase because, e.g., the solid dispersion shows a single broad peak, similar to PVP alone, and lacking a sharp peak for the API (Cao, e.g., pg. 12, Fig. 5).
Brough teaches compositions similar to those of Cao, wherein a drug substance is formulated as an amorphous solid dispersion (Brough, e.g., Example 1, 0107), which is a composite composition in the form of a single-phase miscible composition of two or more pharmaceutical materials (Brough, e.g., 0100), wherein the amorphous carrier character improves the dissolution rate, bioavailability, and solubility characteristics of the API-polymer composite (Brough, e.g., 0090, 0102, and 0110). Brough teaches techniques which enable the formation of a miscible composite (single phase) of one or more pharmaceutical materials even if previously considered immiscible (Brough, e.g., 0100). Brough teaches polymeric carriers provide a stabilizing effect on supersaturated API solutions which improves the dissolution properties of poorly water-soluble drugs (Brough, e.g., 0110). Brough teaches the stabilizing carrier further comprising various functional excipients, e.g., surfactant, stabilizing agent, retardant or similar functional excipient (Brough, e.g., 0070). Brough teaches stearates may be included in the composite (Brough, e.g., 0013 claim 14). Brough clearly suggests the composites may include magnesium stearate (Brough, e.g., 0018).
Brough teaches compositions exhibiting a single glass transition phase are single phase compositions (Brough, e.g., 0153). Cao, e.g., pg. 12, Fig. 5, shows solid amorphous dispersions exhibiting a single glass transition phase. Thus, Cao appears to teach a single phase solid amorphous dispersion as claimed as evidenced by Brough.
Furthermore, the present specification indicates the single phase solid amorphous dispersions may be prepared by solvent evaporation (Specification, e.g., pg. 3:1-14; pg. 7:16-25; and ¶ spanning pp. 8-9). Cao teaches preparing the solid amorphous dispersion using solvent evaporation (Cao, e.g., pg. 8, c2: PREPARATION OF SOLID DISPERSION). The prior art composition is made in the same way proposed by the present specification and appears to be a single phase based on DSC as evident from Cao, e.g., pg. 12, fig. 5.
However, in the event Applicant can show Cao’s compositions are not a single phase, Brough teaches the formation of a solid solution (single phase solid amorphous dispersion) represents the limit of particle size reduction which maximizes the total surface area of the drug in the excipient carrier (Brough, e.g., 0109). Maximizing drug surface area is expected to maximize drug dissolution because the effective surface area is directly proportional to the rate of solute dissolution dC/dt (Brough, e.g., 0108). Thus, the skilled artisan understood the formation of a solid solution corresponding to the claimed feature of a single phase solid amorphous dispersion was desirable for maximizing the effective surface area of the drug and therefore maximizing the rate of dissolution of the drug from the dispersion contributed by the effective surface area of the drug molecules.
It would have been obvious before the effective filing date of the presently claimed invention to formulate Cao’s amorphous dispersions as a single phase solid amorphous solid dispersion since Brough teaches single phase compositions are desirable for improving dissolution, bioavailability, and solubility of active pharmaceutical agents. The skilled would have seen this modification as the use of a known technique to improve similar solid dispersions in the same way. The skilled artisan would have had a reasonable expectation of success because Brough teaches techniques which enable the formation of a miscible composite (single phase) of one or more pharmaceutical materials even if previously considered immiscible.

Cao does not use the term “lubricant” in reference to oleic acid, TWEEN 80 and sodium lauryl sulfate. However, “lubricant” is a functional term referencing the property of compounds, i.e., compounds which exhibit the property of lubricity. Further at least sodium lauryl sulphate was an art recognized lubricant before the effective filing date of the presently claimed invention as evident from Zou (Zou, e.g., claims 1-2). Consequently, Cao as evidenced by Brough and Cao in view of Brough appears to teach a single phase, solid amorphous dispersion comprising an API, an excipient (polymer), and a lubricant (sodium lauryl sulfate) as evidenced by Zou, e.g., claim 1.

Applicable to claim 21: While the combined teachings of Cao and Brough clearly teach a single phase solid amorphous solid dispersion, the combined teachings of Cao and Brough do not expressly teach the single phase solid amorphous dispersion comprising magnesium stearate or sodium stearyl fumarate.
However, Brough clearly suggests composites, e.g., single phase composite compositions may include excipients such as magnesium stearate (Brough, e.g., 0018). Brough teaches techniques which enable the production of a single phase, miscible composite of two or more pharmaceutical materials previously considered to be immiscible for utilization in a secondary processing step (Brough, e.g., 0100). Known techniques enable the formation of a single-phase composite with a variety of known pharmaceutical excipients including stearates (including magnesium stearate) and polymeric materials (Brough, e.g., 0013 and 0118). Brough teaches known techniques for preparing solid dispersions and single-phase materials include melt extrusion and thermokinetic compounding (Brough, e.g., 0107). Brough teaches single phase composites obtained using hot melt extrusion or thermokinetic processing as evidenced by a single Tg (Brough, e.g., 0153 and 0179-0180). Single glass transition is also indicative of amorphous solid solutions (single phase amorphous solid dispersions). See Brough, e.g., 0173. The skilled artisan would have recognized that Brough teaches techniques which enable the formulation of single phase solid amorphous dispersion composites comprising a drug and multiple excipients including polymers and stearates.
Moreover, Zou provides an express suggestion which would have prompted one skilled in the art to modify a single phase, amorphous, solid solution known from the combined teachings of Cao and Brough by including a named lubricant, i.e., magnesium stearate as recited in claim 21 with a reasonable expectation of success.
Zou teaches the addition of lubricant to the API polymer dispersion results in an amorphous dispersion which is as stable or more stable than an amorphous dispersion which contains only the API and the polymer (Zou, e.g., pg. 2/5, Invention Content, ¶ 2). Lubricants include magnesium stearate, sodium stearyl fumarate, and sodium lauryl sulfate (Zou, e.g., pg. 2, Invention Content).
Zou teaches solid dispersions comprising a lubricant (Zou, e.g., claim 1), wherein the lubricant is combinations of lauryl sodium sulfate, magnesium stearate, talc, or silica (Zou, e.g., claim 1).
Zou clearly teaches the lubricant is incorporated within the solid dispersion (Zou, e.g., claim 2):

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This means the lubricant is in the amorphous solid dispersion. Zou uses the term unformed state (amorphous) to characterize the dispersion under accelerated testing conditions (Zou, e.g., pg. 2/25, ¶ 23 and pg. 5, final ¶).
Zou also clearly teaches the lubricant added to the solid dispersion on pg. 3:

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Zou very clearly teaches solid dispersions comprising a lubricant (Zou, e.g., claim 1).
Zou very clearly teaches adding lubricants during the production of the solid dispersion. See Zou, e.g., claim 2:

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It is clearly seen that Zou expressly teaches part of the lubricant is added to the solid dispersion and the remainder of the lubricant is added after the solid dispersion is formed.
Zou exemplifies the addition of lubricant to prepare the solid dispersion. See Zou, e.g., pg. 5, embodiment 5:
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Zou expressly teaches the lubricant magnesium stearate may be used with the lubricant silica, or as an alternative to the lubricant silica, or as an alternative to the lubricant sodium lauryl sulfate as employed by Cao, or in combination with the lubricant sodium lauryl sulfate as employed by Cao. See Zou, e.g., claim 1:

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Additionally, Zou expressly teaches the lubricant sodium stearyl fumarate may be used as an alternative to the lubricant magnesium stearate. See Zou, e.g., pg. 2:

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It would have been obvious before the effective filing date of the presently claimed invention to modify a single phase solid amorphous dispersion comprising an API, one or more pharmaceutically acceptable excipients (PVP), and a lubricant, e.g., sodium lauryl sulfate, as known from Cao and Brough by including magnesium stearate and/or sodium stearyl fumarate in the single phase solid amorphous dispersion as suggested by Zou using techniques for preparing single phase solid dispersions known in the art from Brough with a reasonable expectation of success. The skilled artisan would have been motivated to make this modification to improve the stability of the amorphous API in the composition during storage in the same way suggested by Zou with a reasonable expectation of success. Given the effort required to prepare an amorphous solid dispersion including solid solutions for increased drug dissolution as reported in Brough, the skilled artisan would have used Zou’s technique of adding lubricants such as magnesium stearate to the amorphous dispersion to preserve the amorphous nature of the drug in the same way reported by Zou. The skilled artisan would have had a reasonable expectation of success because Cao teaches compositions comprising combinations of excipients including polymers and lubricants such as sodium lauryl sulfate, because Brough suggests a variety of pharmaceutical excipients are useful for preparing amorphous dispersions including stearates and magnesium stearate, and because Zou suggests lubricants including magnesium stearate, and sodium stearyl fumarate were known and used for the purpose of improving the stability of the amorphous character of poorly water-soluble drugs in similar amorphous dispersion pharmaceutical compositions.

Applicable to claim 22: Brough teaches wherein the solid dispersion composition may include one or more active pharmaceutical ingredients (Brough, e.g., 0089-0091), Examples include antineoplastic agents, cardiovascular agents, etc. (Brough, e.g., 0058). It would have been obvious before the effective filing date of the presently claimed invention to modify compositions suggested by Cao, Brough, and Zou by including additional active agents, such as additional cardiovascular agents with a reasonable expectation of success. the skilled artisan would have viewed this modification as combining known API useful for, e.g., cardiovascular treatment, to arrive at a third composition useful for the same purpose.
Applicable to claim 23, povidone is a pharmaceutical polymer. See Cao, entire document, e.g., Abstract and pg. 8, Table 1 PVP.
Applicable to claims 26, 27, and 28: povidone is poly(vinylpyrrolidone) as recited by instant claims 26 and 27 and 28. Notably, Cao teaches the single phase amorphous solid dispersion comprising povidone and sodium lauryl sulfate, aka, sodium dodecyl sulfate as named in claim 28.
Applicable to claim 29, Cao does not teach a plasticizer. Brough teaches processing agents, including plasticizers are optional (Brough, e.g., 0011 and 0025).
Applicable to claim 31: Cao teaches API to polymer ratio of 1:9 (Cao, e.g., Table 1). Cao does not expressly teach the ratios recited in claim 31. However, Brough teaches API to polymer ratio may be 1:2 or 1:4 (Brough, e.g., 0122, 0138, 0146, 0179). Brough teaches the amount of polymeric carrier is a result effective parameter the skilled artisan would have routinely optimized to achieve an amorphous dispersion depending on the nature of the API in the composition. For example, for the same drug, a ratio of 1:4 drug to polymer results in a fully amorphous dispersion, while a ratio of 1:2 results in a slight amount of crystalline drug (Brough, e.g., 0139). The ratio of 1:4 is a clearly disclosed value recited in claim 31 which is reported in Brough as effective for producing an amorphous dispersion of a poorly water-soluble drug.
Applicable to claim 36: Brough teaches the excipient may include a thermolabile polymeric excipient (Brough, e.g., 0013 and 0093 and 0105 and 0107, 0137, 0140 and 0144 and 0182 and claim 13).
Applicable to claims 37, 41-42 and 54: Cao teaches the composition in a capsule for oral administration (Cao, e.g., pg. 12: Figs. 5-7). Claims 37 and 41 refer to properties of the composition of claim 21. Cao suggests the pharmaceutical compositions have improved dissolution (Cao, e.g., pg. 12, Figs. 6-7). Brough teaches the amorphous carrier character improves the dissolution rate, bioavailability, and solubility characteristics of the API-polymer composite (Brough, e.g., 0090, 0102, and 0110). Since the composition of the cited prior art meets the structural limitations of claim 21, it is assumed properties recited in the present claims are necessarily present. See MPEP 2112.01, I-II. Here, the prior art teaches a specific pharmaceutical composition having each of the elements generically recited in claim 21 arranged in a single-phase amorphous, solid solution. Consequently, the structure taught by the prior art falls within the scope claimed and is presumed to have the same properties observed by Applicant.
Applicable to claim 44: Cao does not teach vemurafenib.
Applicable to claim 46: The combined teachings of Cao, Brough, and Zou teach the same lubricants named by the presently claimed invention. Consequently, the lubricant in the prior art composition would appear meet the limitations of poorly water soluble or water insoluble, and/or crystalline prior to compounding with said active pharmaceutical ingredient to the extent that this product by process limitation limits the subject matter of claim 46. The product by process limitation does not appear to imply any structural difference over the cited prior art since, e.g., the prior art teaches entirely amorphous single phase solid dispersions containing the recited elements.
Accordingly, the subject matter of claims 21-23, 26-29, 31, 35-37, 41-42, 44, 46, and 54 would have been prima facie obvious before the effective filing date of the presently claimed invention, absent evidence to the contrary.

Claims 21, 22, 23, 26-29, 31, 35, 36, 37, 41, 42, 44, 46, and 54 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2015175505 (Lundbeck) in view of Brough, US 20090053315.
Lundbeck teaches formulations comprising an amorphous solid dispersion (Lundbeck, abstract, claims). The solid dispersion comprises API in an amorphous form (Lundbeck, e.g., claim 1). The solid dispersion further comprises a polymer or a combination of at least two polymers (Lundbeck, e.g., claim 4). The solid dispersion further comprises a lubricant, e.g., sodium stearyl fumarate (Lundbeck, e.g., claim 12-13, pg. 11:17-24, pp. 26-28, example 3, Table 1). Hypromellose is a lubricant (Lundbeck, e.g., pg. 32-34). Lundbeck’s solid dispersions contain hypromellose (Lundbeck, e.g., Table 1). Lundbeck’s dispersions also contain sodium stearyl fumarate which is a lubricant named in claim 45 (Lundbeck, e.g., Table 1). Dispersions are in the form of an oral dosage form, e.g., capsule or tablet (Lundbeck, e.g., claim 77). Hypromellose is the pharmaceutical polymer hydroxypropyl methylcellulose (Lundbeck, e.g., pg. 9:32-34). Hydroxypropyl methylcellulose is named in claims 26, 27, and 28). Lundbeck teaches the ratio between hypromellose and API is about 1:4 (Lundbeck, e.g., table 1).
Lundbeck teaches the solid dispersion comprising sodium stearyl fumarate which is a named lubricant in claim 21 as amended.
Lundbeck does not expressly teach the solid amorphous dispersion is a single phase.
Brough cures this deficiency.
Brough teaches solid amorphous dispersions similar to those of Lundbeck, wherein a drug substance is formulated as an amorphous solid dispersion (Brough, e.g., Example 1, 0107), which is a composite composition in the form of a single-phase miscible composition of two or more pharmaceutical materials (Brough, e.g., 0100 and 0153), wherein the amorphous carrier character improves the dissolution rate, bioavailability, and solubility characteristics of the API-polymer composite (Brough, e.g., 0090, 0102, and 0110). Brough teaches techniques which enable the formation of a miscible composite (single phase) of one or more pharmaceutical materials even if previously considered immiscible (Brough, e.g., 0100). Brough teaches polymeric carries provide a stabilizing effect on supersaturated API solutions (Brough, e.g., 0110). Brough teaches the stabilizing carrier further comprising a surfactant (Brough, e.g., 0070). Brough teaches the formation of a solid solution (single phase solid amorphous dispersion) represents the limit of particle size reduction which maximizes the total surface area of the drug in the excipient carrier (Brough, e.g., 0109). Maximizing drug surface area is expected to maximize drug dissolution because the effective surface area is directly proportional to the rate of solute dissolution dC/dt (Brough, e.g., 0108). Thus, the skilled artisan understood the formation of a solid solution corresponding to the claimed feature of a single phase solid amorphous dispersion was desirable for maximizing the effective surface area of the drug and therefore maximizing the rate of dissolution of the drug from the dispersion contributed by the effective surface area of the drug molecules.
It would have been obvious before the effective filing date of the presently claimed invention to formulate Lundbeck’s amorphous dispersions as a single phase solid amorphous dispersion, e.g., a solid solution, since Brough teaches single phase compositions are desirable for improving dissolution, bioavailability, and solubility of active pharmaceutical agents. The skilled would have seen this modification as the use of a known technique to improve similar solid dispersions in the same way. Alternatively, the skilled artisan would have seen this modification as a substitution of one known solid amorphous dispersion for another where each dispersion was known and used for improving solubility, dissolution, and bioavailability of poorly soluble active pharmaceutical compounds. The skilled artisan would have had a reasonable expectation of success because Brough teaches techniques which enable the formation of a miscible composite (single phase) of one or more pharmaceutical materials even if previously considered immiscible.
Applicable to claim 22: Brough teaches wherein the solid dispersion composition may include one or more active pharmaceutical ingredients (Brough, e.g., 0089-0091). It would have been obvious before the effective filing date of the presently claimed invention to modify compositions suggested by Lundbeck by including additional active agents, such as additional agents effective for treating movement disorders with a reasonable expectation of success. The skilled artisan would have viewed this modification as combining known API useful for, e.g., movement disorders, to arrive at a third composition useful for the same purpose.
Applicable to claim 29, Lundbeck does not teach a plasticizer. Brough teaches processing agents, including plasticizers are optional (Brough, e.g., 0011 and 0025).
Applicable to claim 31: Lundbeck teaches API to polymer ratio of about 1:4 (Lundbeck, e.g., pg. 27, Table 1). Brough teaches API to polymer ratio may be 1:2 or 1:4 (Brough, e.g., 0122, 0138, 0146, 0179). Brough teaches the amount of polymeric carrier is a result effective parameter the skilled artisan would have routinely optimized to achieve an amorphous dispersion depending on the nature of the API in the composition. For example, for the same drug, a ratio of 1:4 drug to polymer results in a fully amorphous dispersion, while a ratio of 1:2 results in a slight amount of crystalline drug (Brough, e.g., 0139). The ratio of 1:4 is a clearly disclosed value recited in claim 31 which is reported in Brough as effective for producing an amorphous dispersion of a poorly water-soluble drug.
Applicable to claim 36: Brough teaches the excipient may include a thermolabile polymeric excipient (Brough, e.g., 0013 and 0093 and 0105 and 0107, 0137, 0140 and 0144 and 0182 and claim 13).
Claims 37 and 41 refer to properties of the composition of claim 21. Lundbeck suggests the pharmaceutical compositions have enhanced dissolution (Lundbeck, e.g., pg. 10:5-9). Brough teaches the amorphous carrier character improves the dissolution rate, bioavailability, and solubility characteristics of the API-polymer composite (Brough, e.g., 0090, 0102, and 0110). Since the composition of the cited prior art meets the structural limitations of claim 21, it is assumed properties recited in the present claims are necessarily present. See MPEP 2112.01, I-II. Here, the prior art teaches a specific pharmaceutical composition having each of the elements generically recited in claim 21 arranged in a single-phase amorphous, solid solution. Consequently, the structure taught by the prior art falls within the scope claimed and is presumed to have the same properties observed by Applicant.
Applicable to claim 44: Lundbeck does not teach vemurafenib.
Applicable to claim 46: The combined teachings of Lundbeck and Brough teach the same lubricants named by the presently claimed invention. Consequently, the lubricant in the prior art composition would appear meet the limitations of poorly water soluble or water insoluble, and/or crystalline prior to compounding with said active pharmaceutical ingredient to the extent that this product by process limitation limits the subject matter of claim 46. The product by process limitation does not appear to imply any structural difference over the cited prior art since, e.g., the prior art teaches entirely amorphous single phase solid dispersions containing the recited elements.
Accordingly, the subject matter of claims 21-23, 26-29, 31, 35-37, 41-42, 44, 46, and 54 would have been prima facie obvious before the effective filing date of the presently claimed invention, absent evidence to the contrary.

Claims 21, 22, 23, 26-29, 31, 35, 36, 37, 41, 42, 44, 46, and 54 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2015175505 (Lundbeck) in view of Brough, US 20090053315 and CN 104434809 A (Zou).
The combined teachings of Lundbeck and Brough enumerated above with respect to claims 21, 22, 23, 26-29, 31, 35, 36, 37, 41, 42, 44, 46, and 54 are reiterated here. This rejection is made because while Lundbeck and Brough clearly teach a single phase amorphous solid dispersion containing an API, a polymer, and a lubricant such as sodium stearyl fumarate, the combined teachings Lundbeck and Brough do not expressly teach a single phase amorphous solid dispersion containing an API, a polymer, and magnesium stearate.
Brough clearly suggests composites, e.g., single phase composite compositions may include excipients such as magnesium stearate (Brough, e.g., 0018). Brough teaches techniques which enable the production of a single phase, miscible composite of two or more pharmaceutical materials previously considered to be immiscible for utilization in a secondary processing step (Brough, e.g., 0100). Known techniques enable the formation of a single-phase composite with a variety of known pharmaceutical excipients including stearates (including magnesium stearate) and polymeric materials (Brough, e.g., 0013 and 0118). Brough teaches known techniques for preparing solid dispersions and single-phase materials include melt extrusion and thermokinetic compounding (Brough, e.g., 0107). Brough teaches single phase composites can be obtained using hot melt extrusion or thermokinetic processing as evidenced by a single Tg (Brough, e.g., 0153 and 0179-0180). Single glass transition is also indicative of amorphous solid solutions (single phase amorphous solid dispersions). See Brough, e.g., 0173. The skilled artisan would have recognized that Brough teaches techniques which enable the formulation of single phase solid amorphous dispersion composites comprising a drug and multiple excipients including polymers and stearates.
Zou clearly shows the skilled artisan considered magnesium stearate and sodium stearyl fumarate to be art recognized equivalent lubricants which may be added to solid dispersions to improve stability of non-crystalline forms of the drug in the dispersion. Zou teaches the addition of lubricant to the API polymer dispersion results in an amorphous dispersion which is as stable or more stable than an amorphous dispersion which contains only the API and the polymer (Zou, e.g., pg. 2/5, Invention Content, ¶ 2). Lubricants include magnesium stearate, sodium stearyl fumarate, and sodium lauryl sulfate (Zou, e.g., pg. 2, Invention Content).
It would have been obvious before the effective filing date of the presently claimed invention to modify a single phase solid amorphous dispersion comprising an API, one or more pharmaceutically acceptable excipients (PVP), and a lubricant, e.g., sodium stearyl fumarate, as taught by Lundbeck and Brough by including magnesium stearate as suggested by Zou using techniques for preparing single phase solid dispersions known in the art from Brough with a reasonable expectation of success. The skilled artisan would have been motivated to make this modification to improve the stability of the amorphous API in the composition during storage in the same way suggested by Zou with a reasonable expectation of success. The skilled artisan may have seen this modification as a combination of two known lubricants clearly identified in the prior art as useful for stabilizing amorphous dispersions. Alternatively, the skilled artisan may have seen this modification as a substitution of one known lubricant for another where each were known and suggested as useful for stabilizing amorphous dispersions. The substitution or combination of art recognized equivalents is prima facie obvious. See MPEP 2144.06. The skilled artisan would have had a reasonable expectation of success because Lundbeck teaches compositions comprising combinations of excipients including polymers and lubricants such as sodium stearyl fumarate, because Brough suggests a variety of pharmaceutical excipients are useful for preparing amorphous dispersions including stearates and magnesium stearate, and because Zou suggests lubricants magnesium stearate and sodium stearyl fumarate were known and used for the purpose of improving the stability of the amorphous character of poorly water-soluble drugs in similar amorphous dispersion pharmaceutical compositions. Given the effort required to prepare an amorphous solid dispersion including solid solutions for increased drug dissolution as reported in Brough, the skilled artisan would have used Zou’s technique of adding lubricants such as magnesium stearate to the amorphous dispersion to preserve the amorphous nature of the drug in the same way reported by Zou.
Accordingly, the subject matter of claims 21, 22, 23, 26-29, 31, 35, 36, 37, 41, 42, 44, 46, and 54 would have been prima facie obvious before the effective filing date of the presently claimed invention, absent evidence to the contrary.

Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the claims at issue are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); and In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO internet Web site contains terminal disclaimer forms which may be used. Please visit http://www.uspto.gov/forms/. The filing date of the application will determine what form should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.

Claim(s) 21-23, 26-29, 31, 35-37, 41-42, 44, 46, and 54 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim(s) 1-53, 55-57, 59-62, 64-76 of US Application No. 16185333 in view of Brough, US 20090303630 A1.
Although the claims at issue are not identical, they are not patentably distinct from each other because:
The claims of the reference application are directed to pharmaceutical compositions comprising an amorphous dispersion of an active pharmaceutical ingredient, one or more pharmaceutically acceptable excipients, and a non-polymeric lubricant comprising an agent. The agent may be sodium stearyl fumarate (claim 31). This meets the limitations of the lubricants named in claim 21. The composition may include more than one active pharmaceutical ingredient (claim 32). The composition may include a surfactant (claim 33), polymer (claim 34) or plasticizer (claim 35). The polymers recited in instant claims 26-28 are found in reference application claims 36 and 37. The surfactants recited in instant claim 28 are found in reference application claim 38. The lubricants of instant claim 45 are found in reference patent claims 40-42. The composition may not include a processing agent (claim 48). The composition may not comprise a plasticizer (claim 49). The composition may include an active pharmaceutical ingredient to pharmaceutical excipient ratio of 1 to 4 (claim 50), 3 to 7 (claim 51), 2 to 3 (claim 52), or 1:1 (claim 53). The composition may include a polymer of high melt viscosity (claim 54). The composition may include a thermally labile pharmaceutical polymer (claim 55). The composition may be in the form of a tablet, capsule or sachet (claim 57). The composition does not comprise vemurafenib (claim 31). The non-polymeric lubricant is poorly water soluble or water insoluble and/or crystalline prior to compounding with said active pharmaceutical ingredient (claim 59). The composition of the reference application is silent to the properties recited by instant claims 37 and 41. However, as the composition of the reference patent claims includes all of the structural limitations of required of claim 21, the compositions appear to be capable of achieving the same effects recited in by instant claims 37 and 41.
The claims of the reference application do not expressly teach the composition is a single phase. However, single-phase, amorphous, solid solutions were a known variety of amorphous dispersions as evident from the teachings of Brough as enumerated above. Brough teaches compositions similar to those of reference application claims, wherein a drug substance is formulated as an amorphous solid dispersion (Brough, e.g., Example 1, 0107), which is a composite composition in the form of a single-phase miscible composition of two or more pharmaceutical materials (Brough, e.g., 0100), wherein the amorphous carrier character improves the dissolution rate, bioavailability, and solubility characteristics of the API-polymer composite (Brough, e.g., 0090, 0102, and 0108-0110). Brough teaches techniques which enable the formation of a miscible composite (single phase) of one or more pharmaceutical materials even if previously considered immiscible (Brough, e.g., 0100).
It would have been prima facie obvious before the effective filing date of the presently claimed invention to formulate a pharmaceutical composition comprising an amorphous dispersion of active pharmaceutical ingredient, one or more pharmaceutically acceptable excipients, and non-polymeric lubricant as claimed by the reference application as a single-phase with a reasonable expectation of success. The skilled artisan would have been motivated to make this modification since Brough teaches single phase, amorphous, solid solutions were known and useful for improving dissolution of drugs in the same way as amorphous dispersions because the drug molecules are molecularly dispersed within the composition resulting in a single homogenous amorphous phase. This modification may be viewed as the substitution of one amorphous dispersion for another where each were known for the purpose of improving solubility and bioavailability.
To the extent that the presently claimed invention requires all of the excipients to be amorphous, the claims of the reference patent do not expressly teach the one or more pharmaceutically acceptable excipients are amorphous. However, this feature is taught by Brough, e.g., 0024, and 0099 amorphous composites of two or more pharmaceutical excipients.
It would have been prima facie obvious before the effective filing date of the presently claimed invention to further modify a pharmaceutical composition suggested by the claims of the reference application and Brough by formulating the excipients present in an amorphous form with a reasonable expectation of successfully improving the formulation in the same way suggested by Brough. The skilled artisan would have been motivated to make this modification for improved API dissolution rate, stability, and miscibility of the API as suggested by Brough with a reasonable expectation of success. The skilled artisan would have had a reasonable expectation of successfully modifying compositions suggested by the reference application claims using techniques known from Brough since Brough teaches techniques which enable the production of amorphous composites of two or more pharmaceutically acceptable excipients.
Consequently, the subject matter of the instant claims would be considered to be an obvious variant of the subject matter claimed in the reference application by one skilled in the art.

Response to Arguments
Applicant's arguments filed 10/25/2024 have been fully considered but they are not persuasive.
Applicant has deferred a substantive response until such time as the double patenting rejection is the only remaining rejection.
The rejection is maintained at this time.

Conclusion
No claim is allowed.

Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to WILLIAM A CRAIGO whose telephone number is (571)270-1347. The examiner can normally be reached on Monday - Friday, 9am - 6pm, PDT.
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/WILLIAM CRAIGO/Examiner, Art Unit 1615