Patent Application 17461598 - METHODS AND COMPOSITIONS FOR INHIBITING CD32B - Rejection
Appearance
Patent Application 17461598 - METHODS AND COMPOSITIONS FOR INHIBITING CD32B
Title: METHODS AND COMPOSITIONS FOR INHIBITING CD32B EXPRESSING CELLS
Application Information
- Invention Title: METHODS AND COMPOSITIONS FOR INHIBITING CD32B EXPRESSING CELLS
- Application Number: 17461598
- Submission Date: 2025-05-15T00:00:00.000Z
- Effective Filing Date: 2021-08-30T00:00:00.000Z
- Filing Date: 2021-08-30T00:00:00.000Z
- National Class: 424
- National Sub-Class: 136100
- Examiner Employee Number: 81042
- Art Unit: 1641
- Tech Center: 1600
Rejection Summary
- 102 Rejections: 1
- 103 Rejections: 2
Cited Patents
The following patents were cited in the rejection:
- US 1237837š
- US 0199471š
- US 0121032š
- US 0120103š
Office Action Text
DETAILED ACTION 1. The present application is being examined under the pre-AIA first to invent provisions. 2. 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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 November 25, 2024 has been entered. Claim 9 has been canceled. Claim 9 has been canceled. Claims 1-8 and 10-12 are pending. Claims 11-12 stand withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on May 15, 2024. Claims 1-8 and 10 are currently under consideration. 3. In view of applicantās amendment, following rejections are set forth. 4. Applicantās claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) and under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. However, the two earlier non-provisional applications and all of the provisional applications upon which priority is claimed fails to provide adequate support under 35 U.S.C. 112 for claims 1-8 and 10 of this application. Specifically, insufficient support was identified for the limitation of an antibody having affinity for CD40, the antibody comprising a means for binding CD40 and an IgG1 Fc domain comprising a means for binding CD40 and an IgG1 Fc domain comprising amino acid substitution S267E in the Fc region, wherein the antibody provides enhanced B cell proliferation as compared to a parent antibody comprising the native IgG1 constant chain of SEQ ID NO:4 in the two nonprovisional USSNs 13/301,627 (now US Patent 9,260523) and 12/156,183 (now US Patent 8,063,187). Consequently, the claims have been accorded the priority of the filing date of the parent USSN 14/992,453 (now abandoned) on January 11, 2016. Should Applicant disagree with the Examinerās factual determination above, it is incumbent upon Applicant to provide a showing that specifically supports the instant claim limitations. CLAIM INTERPRETATION 5. The following is a quotation of 35 U.S.C. 112(f): (f) Element in Claim for a Combination. ā An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof. The following is a quotation of pre-AIA 35 U.S.C. 112, sixth paragraph: An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof. 6. The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art. The broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) is limited by the description in the specification when 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is invoked. As explained in MPEP § 2181, subsection I, claim limitations that meet the following three-prong test will be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph: (A) the claim limitation uses the term āmeansā or āstepā or a term used as a substitute for āmeansā that is a generic placeholder (also called a nonce term or a non-structural term having no specific structural meaning) for performing the claimed function; (B) the term āmeansā or āstepā or the generic placeholder is modified by functional language, typically, but not always linked by the transition word āforā (e.g., āmeans forā) or another linking word or phrase, such as āconfigured toā or āso thatā; and (C) the term āmeansā or āstepā or the generic placeholder is not modified by sufficient structure, material, or acts for performing the claimed function. Use of the word āmeansā (or āstepā) in a claim with functional language creates a rebuttable presumption that the claim limitation is to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites sufficient structure, material, or acts to entirely perform the recited function. Absence of the word āmeansā (or āstepā) in a claim creates a rebuttable presumption that the claim limitation is not to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is not interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites function without reciting sufficient structure, material or acts to entirely perform the recited function. Claim limitations in this application that use the word āmeansā (or āstepā) are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action. Conversely, claim limitations in this application that do not use the word āmeansā (or āstepā) are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action. This application includes one or more claim limitations that use the word āmeansā or āstepā but are nonetheless not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph because the claim limitation(s) recite(s) sufficient structure, materials, or acts to entirely perform the recited function. Such claim limitation(s) is/are: āan antibody having affinity for CD40, the antibody comprising a means for binding CD40ā in independent claim 1. Specifically, the independent claim 1 recites āmeans for binding CD40ā and thus satisfies prongs āAā and āBā. However, the claim does not satisfy prong āCā which requires that āthe generic placeholder is not modified by sufficient structure, material, or acts for performing the claimed functionā. Here, independent claim 1 modifies the āmeans for binding CD40ā to necessarily have the structure of being āan antibodyā, therefore, the claim does provide structural limitations concerning the āmeansā that is binding CD40 so that is not generic. For example, CD154 is a known endogenous ligand for CD40 and is a type II transmembrane protein, a member of TNF superfamily having the structure of β-sheet, α-helix loop, and a β-sheet [see Elgueta et al. Immunol Rev. 2009 May 229(1):1-31, particularly Introduction in page 2). However, CD154 cannot serve as āmeans for binding CD40ā even though it is the naturally ligand for CD40 and binds CD40 because it is not an antibody as required by the independent claim 1. Therefore, it is clear that the recited āmeansā is modified by structure of having to be an antibody rather than being a generic means with no structural limitation as required under 35 USC 112(f). Because this/these claim limitation(s) is/are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, it/they is/are not being interpreted to cover only the corresponding structure, material, or acts described in the specification as performing the claimed function, and equivalents thereof. If applicant intends to have this/these limitation(s) interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, applicant may: (1) amend the claim limitation(s) to remove the structure, materials, or acts that performs the claimed function; or (2) present a sufficient showing that the claim limitation(s) does/do not recite sufficient structure, materials, or acts to perform the claimed function. 7. The following is a quotation of 35 U.S.C. 112(b): (b) CONCLUSION.āThe specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention. The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph: The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention. 8. Claim 10 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Claim 10 recites the limitation "the kit of claim 8". There is insufficient antecedent basis for this limitation in the claim. The previous claim 8 does not recite a kit. 9. The following is a quotation of the first paragraph of 35 U.S.C. 112(a): (a) IN GENERAL.āThe specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention. The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112: The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention. 10. Claims 1-8 and 10 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. The amended claims are now drawn to an antibody having affinity for CD40, the antibody comprising a means for binding CD40 and an IgG1 Fc domain comprising amino acid substitution S267E, wherein the antibody provides enhanced B cell proliferation as compared to the antibody that does not comprises S267E in the Fc region. Dependent claims 3-8 further encompass a pharmaceutical composition comprising the antibody of claim 1 and wherein the pharmaceutically acceptable carrier comprises an aqueous solution, formulated for injection, a sustained release formulation, or further comprising a chemotherapeutic agent such as taxane. Dependent claim 10 still recites a kit and taxane. The specification discloses examples of anti-CD40 antibody clones PFCD40, S2C6, G28.5, and 5D12 with amino acid substitutions S267E/L328F in the Fc region (e.g. see Figures 34A and 34B) and shows that the anti-CD40 antibodies having S267E/L328F amino acid substitutions in the Fc region have enhanced binding to FcγRIIb and increased B cell proliferation. However, other antibodies such as anti-CD20 antibody, anti-CD52 antibody, and anti-CD19 antibody having the same S267E/L328F amino acid substitutions do not have the effect of enhancement of B cell proliferation. Figure 55 in the instant specification discloses relative B cell viability in the presence of one IgG1 Fc variant S267E anti-CD40 antibody 5D7. However, there is insufficient written description in the specification as-filed of the claimed antibody having affinity for CD40, the antibody comprising a means for binding CD40 and an IgG1 Fc domain comprising S267E substitution, wherein the antibody provides enhanced B cell proliferation as compared to the antibody that does not comprise S267E in the Fc region. The instant application has not provided a sufficient description showing possession of the necessary functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the genus of the antibody having affinity for CD40, the antibody comprising a means for binding CD40 and an IgG1 Fc comprising S267E, as well as the pharmaceutical composition thereof formulated in a water-soluble form, for injection, comprising a chemotherapeutic agent including taxane, and a kit thereof broadly recited in the instant claims. For example, the specification speculates that the activation of B cell observed maybe due to the agonist nature of the anti-CD40 antibodies used (see [345] in page 117 of the specification as-filed). The instant specification further discloses examples of in vitro B cell proliferation assays and shows that anti-CD40 antibody clone 5D12 with amino acid substitution S267E/L328F promotes B cell proliferation similar to wild type anti-CD40 antibody clone S2C6 (without mutation in the Fc region) but this was not observed in other agonist anti-CD40 antibodies with or without S267E/L328F substitution. As evidenced by Hager et al. (Scandinavian Journal of Immunology 2003, 57:517-524), both anti-CD40 antibody clones 5D12 and S2C6 are moderate activators of B cells and clone G28.5 is potent activator of B cells (e.g. see 1st paragraph in left col. in page 520). It is also not clear whether the single species of anti-CD40 antibody clone 5D7 having single amino acid substitution S267E as claimed would support the entire genus of the antibody as claimed. As such, it does not appear that the instant specification provided sufficient description showing possession of the necessary functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show that applicant was in possession of the genus of antibody recited in the instant claims. Note that the written description doctrine requires that sufficient representing species be disclosed in order to support the entire genus. Rather than simply listing various embodiments, the usual approach is to also describe common structural features of the species. See Regents of the University of California v. Eli Lilly & Co., 119 F.3d 1559 (Fed. Cir. 1997) and Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1355 (Fed. Cir. 2010). In Abbvie Deutschland Gmbh & Co KG, Abbvie Bioresearch Center, Inc.,and Abbvie Biotechnolo~, Ltd., v. Janssen Biotech In. And Centocor Biologics,LLC, Case No. 2013-1338 and 2013- 1346, C.A.Fed. ("Abbvie"), the Federal Circuit reiterates the inherent unpredictability of protein engineering in Abbvie. For example, functionally defined genus claims can be inherently vulnerable to invalidity challenge for lack of written description support, especially in technology fields that are highly unpredictable, where it is difficult to establish a correlation between structure and function for the whole genus or to predict what would be covered by the functionally claimed genus. Ariad, 598 F.3d at 1351 ("[T]he level of detail required to satisfy the written description requirement varies depending on the nature and scope of the claims and on the complexity and predictability of the relevant technology."); see also Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341, 1352 (Fed. Cir. 2011) (noting the technical challenges in developing fully human antibodies of a known human protein). It is true that functionally defined claims can meet the written description requirement if a reasonable structure-function correlation is established, whether by the inventor as described in the specification or known in the art at the time of the filing date. Enzo Biochem, Inc. v. Gen- Probe Inc., 323 F.3d 956, 964 (Fed. Cir. 2002). However, the record here does not indicate such an established correlation. Instead, AbbVie used a trial and error approach to modify individual amino acids in order to improve the IL-12 binding affinity.ā It should be noted that recent court cases have indicated that recitation of an antibody which has specific functional properties in the absence of knowledge of the antibody sequences that give rise to said functional properties do not satisfy the requirements for written description. See for example AbbVie Deutschland GmbH v. Janssen Biotech. Inc. 759 F.3d 1285 (Fed. Cir. 2014) discussed above as well as Amgen v. Sanofi, (Fed Cir, 2017-1480. 10/5/2017). Indeed, in Amgen Inc. v. Sanofi, No. 17-1480 (Fed. Cir. 2017), the court indicates that that it is improper to allow patentees to claim antibodies by describing something that is not the invention, i.e. the antigen, as knowledge of the chemical structure of an antigen does not give the required kind of structure-identifying information about the corresponding antibodies, with the antibody-antigen relationship be analogized as a search for a key on a ring with a million keys on it. It does not appear based upon the limited disclosure of a single anti-CD40 antibody clone 5D7 consisting S267E substitution in the in vitro experiments (showing relative viability) alone that Applicant was in possession of the necessary common attributes or features of the elements possessed by the members of the genus in view of the limited number of species disclosed and the extensive variation permitted within the genus the antibody having affinity for CD40, the antibody comprising a means for binding CD40 and an IgG1 Fc domain comprising S267E substitution. āAdequate written description requires a precise definition, such as by structure, formula, chemical name or physical properties, not a mere wish or plan for obtaining the claimed chemical invention.ā Regents of the University of California v. Eli Lilly and Co. 43 USPQ2d 1398 (Fed. Cir. 1997). The disclosure must allow one skilled in the art to visualize or recognize the identity of the subject matter of the claim. Id. 43 USPQ2d at 1406. In the absence of disclosure of relevant, identifying characteristics of antibody having affinity for CD40, the antibody comprising a means for binding CD40 and an IgG1 Fc domain having S267E, there is insufficient written disclosure of the claims under 35 U.S.C. 112, first paragraph. Applicantās arguments in conjunction with the various legal citations including Ex parte Chamberlain have been fully considered but have not been found persuasive. Applicant assets that the recitation of āmeansā plus function for binding CD40 would mean no requirement for written description. Applicant appears to argue that there were two parts of means-plus-function under 35 USC 112 sixth: PNG media_image1.png 360 664 media_image1.png Greyscale PNG media_image2.png 58 672 media_image2.png Greyscale This is not found persuasive for following reasons: Applicantās identification of the one species of the antibody in Figure 55 in the instant specification is acknowledged. However, applicant appears to asserts that only two prongs are necessary to invoke 112 sixth paragraph, namely, the function of āmeans for binding CD40ā and corresponding structure in Figure 55 in the instant specification. However, as discussed above, the claims fail to satisfy prong C and therefore the claims are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, it/they is/are not being interpreted to cover only the corresponding structure, material, or acts described in the specification as performing the claimed function, and equivalents thereof. As such, applicantās arguments relying upon āmeans-plus-functionā have not been found persuasive. Applicant further asserts that Figure 55, originally disclosed as FIG.10 in the ā174 provisional application was later incorporated-by-reference. Note that Figure 55 was not filed in the two parent USSNs 12/156,183 (now US Patent 8,063,187) and 13/301,627 (now US Patent 9.260,526). Applicant asserts that the instant specification discloses that S267E substitution in any Fc region could increase FcγRIIB binding. Applicant asserts that Figure 34A of the instant application discloses anti-CD40 antibody having S267E/L328F enhanced B cell proliferation. This is not found persuasive because Figure 34A does not teach CD40 antibody comprising S267E substitution wherein the antibody enhanced B cell proliferation as compared to a parent antibody comprising the native IgG1 constant chain of SEQ ID NO:4 (see copy of Figure 34A below for applicantās convenience): PNG media_image3.png 482 670 media_image3.png Greyscale Applicant further argues in Figure 34B, each of the anti-CD40 antibodies 5D12, S2C6, and G28.5 having two mutations including S267E and L328F showed enhanced B cell proliferation compared to antibody that consisting of G236R/L328R. This is not found persuasive because the anti-CD40 antibodies in Figure 34B consists two substitutions S267E/L328F and nowhere in the specification discloses that L328F can be removed or that S267E and S267E/L328F are equivalent of each other. Note that the anti-CD40 antibodies consisting of substitutions S267E/L328F which is not sufficient to support the genus of any anti-CD40 antibody comprising S267E substitution since the critical part of the substitution L328F was omitted in the claims. Figure 34B shows that anti-CD40 antibody 5D12 consisting S267E/L328F has more B cell proliferation compared to other antibody clones such as S2C6 S267E/L328F, S2C6 G238R/L328R, it has less B cell proliferation compared to CD40 S2C6 WT IgG1 without S267E. In fact, Figure 34B shows that CD40 S2C6 WT-IgG1 promotes most B cell proliferation than all CD40 antibody clones either WT or consisting S267E/L328F or G236R/L328R. See Figure 34B copy shown below for applicantās convenience: PNG media_image4.png 420 586 media_image4.png Greyscale As such, Figure 34B shows the opposite as the instant amended claim 1wherein the CD40 antibodies comprising S267E/L328F reduced B cell proliferation compared to the parent antibody comprising wild type IgG constant region. Once again, the sole portion of the specification that discloses anti-CD40 antibody consisting S267E substitution is Figure 55 which discloses in vitro B cell viability in the presence of anti-CD40 5D7 IgG1 (wild type Fc without mutations) and anti-CD40 antibody 5D7 consisting S267E substitution. It appears that when antibody concentration is within 10 ng/ml-1000ng/ml, the anti-CD40 antibody with S267E substitution in the Fc region enhanced B cell proliferation more than the anti-CD40 antibody without S267E substitution. The single species of anti-CD40 antibody 5D7 consisting S267E substitution is not sufficient to support any or all antibody having affinity for CD40, the antibody comprising a means for binding CD40 and an IgG1 Fc domain comprising S267E, wherein the antibody provides enhanced B cell proliferation as compared to the antibody that does not comprise S267E (but could have any or all unidentified substitutions in the Fc region). Applicantās own assertion indicates that it was unpredictable in making anti-CD40 antibody with S267E substitution. For example, applicant asserts in the past paragraph in page 17 of the REMARK filed on February 25, 2025: PNG media_image5.png 84 640 media_image5.png Greyscale The specification concludes that ā[i]n the case of CD40, this may be the result of its role as a positive regulator of B cell activation via engagement at the T cell interface. It is known that some of the antibodies used are agonist, that is to say that their binding of CD40 on B cells and other cells promotes positive signaling and activation of B cells. In a sense these antibodies are mimicking the co-activation signal of a T cell. The antibody (and thus epitope) dependence of this activation is likely related to the capacity of the antibodies to agonize. The reason for the enhanced agonism and stimulation of the B cells upon high affinity (S267E/L328F) engagement of Fc.gamma.RIIb, but not using WT IgG1 or Fc-KO, is not currently clear, and requires further studyā (see [345] in page 117 of the specification as-filed). The claims recite a genus of antibody having affinity for CD40, the antibody comprising a means for binding CD40. While it is not clear if the binding of CD40 is agonist or antagonist for the target cells. Further, anti-CD40 antibody 5D7 consisting S267E substitution does not enhance B cell proliferation as compared to the 5D7 wildtype antibody without S267E substitution. Once again, it should be noted that recent court cases have indicated that recitation of an antibody which has specific functional properties in the absence of knowledge of the antibody sequences that give rise to said functional properties do not satisfy the requirements for written description. See for example AbbVie Deutschland GmbH v. Janssen Biotech. Inc. 759 F.3d 1285 (Fed. Cir. 2014) discussed above as well as Amgen v. Sanofi, (Fed Cir, 2017-1480. 10/5/2017). Indeed, in Amgen Inc. v. Sanofi, No. 17-1480 (Fed. Cir. 2017), the court indicates that that it is improper to allow patentees to claim antibodies by describing something that is not the invention, i.e. the antigen, as knowledge of the chemical structure of an antigen does not give the required kind of structure-identifying information about the corresponding antibodies, with the antibody-antigen relationship be analogized as a search for a key on a ring with a million keys on it. The disclosure of a single anti-CD40 antibody consisting of S267E substitution showing more B cell proliferation compared to the wild type anti-CD40 antibody without amino acid substitution at antibody concentration 100-1000 ng/ml are not sufficient to support the broad genus of anti-CD40 antibody unrestricted in their variable region structure, epitope to which they bind, functions (antagonist vs agonist), mechanism of action (e.g. promotes B cell proliferation via antigen binding or Fc binding). Nor does the specification provide a structure-function relationship sufficient to allow a person of ordinary skill in the art to visualize or recognize members of the genus. As such, applicantās arguments have not been found persuasive. 11. 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. 12. The following is a quotation of the appropriate paragraphs of pre-AIA 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action: A person shall be entitled to a patent unless ā (b) the invention was patented or described in a printed publication in this or a foreign country or in public use or on sale in this country, more than one year prior to the date of application for patent in the United States. 13. Claims 1-8 and 10 are rejected under pre-AIA 35 U.S.C. 102(b) as being anticipated by Zhang et al. (US 2014/0120103). Given that the instant claims are recorded the priority date of January 11, 2016 (the filing date of parent USSN 14/992,453, now abandoned) for the reasons stated above, Zhang et al. is qualified as 102(b) type of prior art. Zhang et al teach an anti-CD40 antibody comprising S267E substitution in the Fc region having increased binding affinity to FcγRIIb, increased ADCC or increased anti-CD40 agonist activity (e.g. see [0044] and [0067]). Zhang et al. teach examples of anti-CD40 antibody such as SGN-40, a humanized IgG1 antibody from mouse clone S2C6 (e.g. see [0017]). Zhang et al. teach specific working example of anti-CD40 antibody APX005 consisting of S267E substitution showing increased agonist activity compared to the parent APX005 without substitution (e.g. see FIG. 21 and [0094]). Zhang et al. teach that the anti-CD40 antibodies can be formulated into a pharmaceutical composition comprising a pharmaceutically acceptable carrier that is a solution for injection (e.g. see [0221]) and can also be in solid form which is considered a sustained release formulation (e.g. see [0227]). Zhang et al. teach composition comprising the anti-CD40 antibody together with other therapeutic agents such as a chemotherapeutic agent (e.g. see [0235]-[0236]) or a cytotoxin including paclitaxel which is a known taxane. Further, Zhang et al. teach a kit comprising the anti-CD40 antibody (e.g. see [0266]). Therefore, the reference teachings anticipate the instant invention. 14. The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action: (a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made. This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a). 15. Claims 1-5 stand rejected under 35 U.S.C. 103(a) as being unpatentable over Dahiyat et al. (US 2006/0121032) in view of de Goer de Herve et al. (Blood 15 October 2005, 106;8:2806-2814), Vonderheide et al. (Journal of Clinical Oncollogy March 1, 2007, 25;7:876-883) and Dhodapka et al. (PNAS February 22, 2005, 102;8:2910-2915) for the reasons of record. Dahiyat et al. teach antibody Fc variants comprising amino acid substitutions in the Fc region, wherein the antibody binds target antigens and the Fc variants exhibits increased binding affinity to FcγRIIb, specifically, variant 338 S267E (serine in position 267 being substituted by glutamic acid) made in the context of two antibodies comprising human IgG1 Fc region: alemtuzumab (anti-CD52 antibody) and PRO70769 (an anti-CD20 antibody) (showing over 90 fold increase in binding affinity to FcγRIIb relative to the wild type parent Fc having serine in position 267 (e.g. see Figure 15 and Example 1). Dahyiat et al. state āFc variants may be constructed in a parent Fc polypeptide irrespective of its context. That is to say that, the sole criteria for a parent Fc polypeptide is that it comprise an Fc regionā (see [0096]) and explicitly named well-known anti-cancer antibody including anti-CD40 antibodies such as SGN-40 and toralizumab (e.g. see paragraph [0207] on pages 34-35). Dahiyat et al. teach that antibody Fc variants with enhanced binding to FcγRIIb than parent antibody comprising unmodified Fc region can act as FcγRIIb agonist or antagonist, wherein the antagonist is capable of modulating B cell proliferation via binding to the Fc/ FcγRIIb binding site but failing to trigger or reducing cell signaling, thereby enhance the effect of antibody-based anti-cancer therapy (e.g. see paragraphs [0117]-[0118] on page 16). Dahiyat et al. teach pharmaceutical compositions comprising the Fc variant (e.g. see [0190]). Further, Dahyiat et al. teach that the antibody Fc variant with enhanced FcγRIIb affinity can coengage the FcγRIIb and the target antigen on the surface of the same immune cell, thereby inhibiting proliferation, apoptosis, or other anti-proliferative effect; or antigen and FcγRIIb coengagement on the same cell may be advantageous when the Fc variant is being used to modulate the immune system (e.g. see paragraph [0124] on page 18). Dahyiat et al. method of enhancing macrophage activation by administering the antibody variant (e.g. see claims 1-9). The reference teachings differ from the claimed invention by not exemplifying an anti-CD40 antibody Fc variant comprising S267E amino acid substitution in the Fc region. de Goer de Herve et al. teach that injection of agonistic anti-CD40 antibody in mice lead to optimal activation of CD8 T cells (e.g. see right column in page 2806). de Goer de Herve et al. further teach that agonistic anti-CD40 antibody could lead to better immune response to pathogens or tumors (e.g. see right column on page 2813). Vonderheide et al. teach that CD40, a member of tumor necrosis factor receptor (TNFR) superfamily on dendritic cells and B cells, regulates immune activation, mediates tumor apoptosis, and is considered a target for cancer therapy (e.g. see left column on page 876). Vonderheide et al. further teach that the fully human anti-CD40 agonist monoclonal antibody CP-870,893 has both direct and indirect effect on tumor cell death; it activates human antigen presenting cells in vitro and inhibits human tumor growth in vivo (e.g. see pages 876-877). Vonderheide et al. teach that infusion of the anti-CD40 antibody in a pharmaceutical composition in human globally activates peripheral blood B cells and dendritic cells (e.g. see page 882). Given that the antibody was infused to human patients, it would be in a soluble-form without evidence to the contrary. Dhodapkar et al. teach that dendritic cells are highly differentiated APC cells that play a key role in the initiation and regulation of T cell immunity to pathogens and tumors (e.g. see left column on page 2910). The reference teaches that dendritic cells express both activating and inhibitory Fcγ receptors; antibodies (e.g. clone 2B6) selectively block the inhibitory Fcγ (FcγRIIb) leads to spontaneous and full dendritic cell (DC) maturation, making them capable of presenting antigen from antibody-coated tumor cells and generating tumor-specific T cells without the need for a further maturation stimulus (e.g. see pages 2910-2911). Dhodapkar et al. teach blockage of the inhibitory FcγRIIb on DCs leads to enhanced tumor-specific T cells (e.g. left column on page 2915). Dhodapkar et al. expression of the inhibitory FcγRIIb on B cells is critical in maintaining peripheral tolerance (e.g. see right column on page 2915). The reference concludes that blockage of FcγRIIb leads to the induction of antitumor immunity without the need for exogenous maturation stimuli and can boost T cell response by means of monoclonal antibodies in vivo; blocking FcγRIIb can improve the efficacy of monoclonal antibodies against cancer of infection (e.g. see right column on page 2915). It would thus be obvious to one of ordinary skill in the art at the time the invention was made to modify the anti-CD40 antibody of de Goer de Herve et al. or Vonderheide et al. following the teachings of Dahiyat et al. regarding making Fc variant with enhanced binding affinity to FcγRIIb. The ordinary artisan at the time the invention was made would have been motivated to do so, and have a reasonable expectation of success, since both anti-CD40 antibody (e.g. agonistic anti-CD40 antibody taught by de Goer de Herve et al. or Vonderheide et al.) and blocking anti-FcγRIIb antibody (e.g. those taught by Dhodapkar et al.) can enhance DC and B cell function for the desired antitumor immunity. A single antibody comprising Fc variants with enhanced affinity to FcγRIIb (e.g. anti-CD40 antibody Fc variants) can be produced by method described by Dahiyat et al. to coengage CD40 antigen and FcγRIIb for in vitro or in vivo studying cancer therapy. Additionally, Dahiyat et al. also specifically discloses that anti-CD40 antibodies including SGN-40 and toralizumab can be modified in the Fc region by mutating S267E. Given that such anti-CD40 antibody with S267E substitution has the same structure as the antibody recited in the instant claims, the prior art anti-CD40 antibody would inherently/intrinsically have the function of enhanced B cell proliferation as compared to a parent antibody comprising the native IgG1 constant chain of SEQ ID NO:4. Applicantās arguments have been fully considered but have not been found persuasive. Applicant continues to argue that Dahiyat does not teach S267E mutation in the Fc region can be applied to any anti-CD40 antibodies. Applicant further asserts that the passages cited by the examiner teaches the opposite effect, namely, inhibits B cell proliferation. Applicant asserts that Dahiyat et al. teaches anti-CD20 antibody and is not applicable to anti-CD40 antibody. Applicant also argues that Voderheide and De Goer de Herve fail to provide link between anti-CD40 antibody to combine with S267E substitution enabling binding to FcγRIIb and enhance B cell proliferation. Applicant asserts that Vonderheide and De Goer de Herve both teach agonist anti-CD40 antibodies has a high risk of autoimmunity. As such, applicant argues the references do not suggest the claimed invention with a reasonable expectation of success. Furthermore, applicant asserts that the Examiner neglected the post filing date references regarding the advancement in anti-CD40 antibody therapy. Applicant states: PNG media_image6.png 338 690 media_image6.png Greyscale Applicant argues that even well after the effective filing date of the instant application increased affinity to FcγRIIb of anti-CD40 antibodies was unexpected and not fully understood in the art. As such, applicant asserts that the rejection should be withdrawn. This is not found persuasive for following reasons: Contrary to applicantās arguments that Dahiyat does not teach anti-CD40 antibody with S267E substitution, note that applicant appears to ignore that Dahiyat et al. teaches S267E substitution in two antibodies: alemtuzumab (anti-CD52 antibody) and PRO70769 (an anti-CD20 antibody) (showing over 90 fold increase in binding affinity to FcγRIIb relative to the wild type parent Fc having serine in position 267 (e.g. see Figure 15 and Example 1). Dahyiat et al. state āFc variants may be constructed in a parent Fc polypeptide irrespective of its context. That is to say that, the sole criteria for a parent Fc polypeptide is that it comprise an Fc regionā (see [0096]) and explicitly named well-known anti-cancer antibody including anti-CD40 antibodies such as SGN-40 and toralizumab (e.g. see paragraph [0207] on pages 34-35). As such, Dahiyatās teachings is not limited to only anti-C20 antibody Fc variant but rather include that the S267E substitution can be made in the Fc region of an anti-CD40 antibody since Fc is common in all IgG1 antibody. Once again, contrary to applicantās arguments of improved clinical efficacy of anti-CD40 antibody having FcγRIIb binding being unexpected as taught by Li and Ravetch, note that the post-filing date reference teaches only agonistic anti-CD40 antibody while the instant claims read on any antibody having affinity for CD40 and FcγRIIb on a B cell or dendritic cell. As such, the unexpected results shown by the post-filing date reference (Li and Ravetch) are not commensurate in scope with the instant claims. Further, Li and Ravetch (Science 2011, 333;1030-1034, reference on IDS) teach that agonist anti-CD40 antibodies have been developed for immunotherapy and coengaging CD40 with agonist anti-CD40 antibody and FcγRIIB is required for immune activation (e.g. see Abstract). These teachings of Li and Ravetch were disclosed by prior art references cited by the Examiner. For example, Dahiyat et al. teach FcγRIIb coengagement on the same cell may be advantageous when the Fc variant is being used to modulate the immune system (e.g. see paragraph [0124] on page 18). Dahiyat et al. specifically teach that S267E amino acid substitutions in antibodies such as anti-CD40 antibody can achieve the purpose of coengaging CD40 and FcγRIIB (e.g. see paragraph [0124] on page 18 and paragraph [0207] on pages 34-35). Furthermore, contrary to applicantās assertion of doubting of therapeutic effect of anti-CD40 antibody, note that the claims are drawn to a product: an antibody having affinity for CD40 comprising a means for binding CD40 and an IgG1 Fc region comprising S267E. An ordinary skill in the art does not have to produce such antibody for therapy since it is not required to meet the claimed limitation. Rather, an ordinary skill in the art would have been motivated to product the claimed antibody for research and animal studies in view of the teachings of the cited prior art. Here, Vonderheide et al. teach that CD40, a member of tumor necrosis factor receptor (TNFR) superfamily on dendritic cells and B cells, regulates immune activation, mediates tumor apoptosis, and is considered a target for cancer therapy (e.g. see left column on page 876). Vonderheide et al. further teach the fully human IgG1 anti-CD40 agonist monoclonal antibody CP-870,893 has both direct and indirect effect on tumor cell death; it activates human antigen presenting cells in vitro and inhibits human tumor growth in vivo (e.g. see pages 876-877). Vonderheide et al. teach that infusion of the anti-CD40 antibody in human patients with solid tumors (melanoma, noon-small cell lung cancer, sarcoma, breast cancer, thyroid cancer, unknown primary, mesothelioma) globally activates peripheral blood B cells and dendritic cells (e.g. see Table 1 in page 877 and page 882). Dhodapkar et al. teach blockage of the inhibitory FcγRIIb on DCs leads to enhanced tumor-specific T cells (e.g. left column on page 2915). Dhodapkar et al. expression of the inhibitory FcγRIIb on B cells is critical in maintaining peripheral tolerance (e.g. see right column on page 2915). The reference concludes that blockage of FcγRIIb leads to the induction of antitumor immunity without the need for exogenous maturation stimuli and can boost T cell response by means of monoclonal antibodies in vivo; blocking FcγRIIb can improve the efficacy of monoclonal antibodies against cancer of infection (e.g. see right column on page 2915). Thus, an ordinary skill in the art would know that agonist anti-CD40 antibody can be administered to treat cancer and a single amino acid substitution S267E in the known agonist anti-CD40 antibody would be expected to enhance the anti-tumor activity by coengaging the CD40 and the inhibitory FcγRIIb receptor resulting in enhanced tumor-specific T cell and breaking peripheral tolerance (See Dhodapkar et al., right col. in page 295). Moreover, contrary to applicantās assertion of lack of motivation to combine, note that the obviousness inquiry does not ask "whether the references could be physically combined but whether the claimed inventions are rendered obvious by the teachings of the prior art as a whole." In re Etter, 756 F.2d 852 (Fed. Cir. 1985) (en banc); see also In re Keller, 642 F.2d 413 (CCPA 1981) (stating "[t]he test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference"). Rather, in a case such as this where each of the elements of the claim are known to the art, the obviousness inquiry requires a finding that the combination of known elements was obvious to a person with ordinary skill in the art. Here, the prior art of record provides strong motivation to treat cancer by administering the anti-human CD40 antibody comprising S267E substitution in the Fc region for enhanced binding to FcγRIIb. For example, Vonderheide et al. teach agonist anti-CD40 antibody was well tolerated and biologically active and was associated with antitumor activity (e.g. see Conclusion in page 876). Vonderheide et al. also teach that considerable data demonstrate that signaling via CD40 activates antigen-presenting cells including dendritic cells and B cells (e.g. see left col. in page 876) in tumor bearing host, CD40 agonist antibody triggers effective immune response against tumor-associated antigen (e.g. see right col. in page 876); and fully human and selective anti-CD40 agonist monoclonal antibody can activate human antigen presenting cell in vitro and inhibit human tumor growth in mice models (see lines 1-4 in left col. in page 877). While de Goer de Herve et al. caution the risk of autoimmunity, nonetheless, teach that agonistic anti-CD40 antibody could lead to better immune response to pathogens or tumor that are immune tolerant (escaping from the immune system) (e.g. see lines 2-6 in right col. in page 2813). In addition, Dahiyat et al. discloses that anti-CD40 antibodies are anti-cancer antibodies (e.g. see [0207]). As such, there are ample evidence in the prior art to support the use of anti-CD40 antibody to treat human cancer at the time the invention was filed. Additionally, Dahiyat et al. teach Fc variants that provide enhanced binding to the inhibitory receptor FcγRIIb provide an enhancement to the IVIG therapeutic approach. In particular, the Fc variants of the present invention that bind with greater affinity to the FcγRIIb receptor than parent Fc polypeptide may be used. Such Fc variants would thus function as FcγRIIb agonists, and would be expected to enhance the beneficial effects of IVIG as an autoimmune disease therapeutic and also as a modulator of B-cell proliferation. Thus, an ordinary skill in the art would know at the time the invention was filed that modifying anti-CD40 antibody (e.g. agonist antibody disclosed by de Goer de Herve et al. or Vonderheide et al.) by incorporating amino acid substitution in the Fc region such as S267E (showing 90 fold increase in binding to FcγRIIb relative to the unmutated Fc region) would be helpful in reducing autoimmunity risk in anti-CD40 therapy since FcγRIIb is an inhibitory receptor for the Fc region in view of the teachings of Dahiyat et al. Dhodapkar et al. teach that dendritic cells express both activating and inhibitory Fcγ receptors; antibodies (e.g. clone 2B6) selectively block the inhibitory Fcγ (FcγRIIb) leads to spontaneous and full dendritic cell (DC) maturation, making them presenting antigen from antibody-coated tumor cells and generating tumor-specific T cells without the need for a further maturation stimulus (e.g. see pages 2910-2911). Dhodapkar et al. teach blockage of the inhibitory FcγRIIb on DCs leads to enhanced tumor-specific T cells (e.g. left column on page 2915). Dhodapkar et al. expression of the inhibitory FcγRIIb on B cells is critical in maintaining peripheral tolerance (e.g. see right column on page 2915). The reference concludes that blockage of FcγRIIb leads to the induction of antitumor immunity without the need for exogenous maturation stimuli and can boost T cell response by means of monoclonal antibodies in vivo; blocking FcγRIIb can improve the efficacy of monoclonal antibodies against cancer of infection (e.g. see right column on page 2915). It is noted that the anti-FcγRIIb antibody 2B6 used by Dhodapkar et al. can compete for immune complex binding to the FcγRIIb and thus, one of ordinary skill in the art would understand that the 2B6 antibody binds the same region on FcγRIIb as the Fc region of an antibody. Thus, Fc variant having enhanced binding to FcγRIIb would be expected to have similar function and the blocking antibody 2B6 ā namely induce spontaneous and full dendritic cell maturation, making them presenting antigen from antibody-coated tumor cells and generating tumor-specific T cells. Therefore, one of ordinary skill would be motivated to modify the anti-CD40 antibody by making simple amino acid substitution S267E in the Fc region with reasonable expectation of success, because the S267E substitution in the Fc region would enhance the binding of the antibody to FcγRIIb on B cell and dendritic cells leading to enhanced tumor-specific T cells; such modification would further enhance the effect of agonistic anti-CD40 antibody (known to have the function of activating antigen-presenting cells including dendritic cells and B cells). Note that all that is required is a reasonable expectation of success, not absolute predictability of success, see In re OāFarrell, 853 F.2d 894, 903 (Fed. Cir. 1988). Contrary to applicantās arguments of lack of motivation to combine the reference for the method of cancer treatment and unexpected results, note that any differences between the claimed invention and the prior art may be expected to result in some differences in properties. The issue is whether the properties differ to such an extent that the difference is really unexpected. The claimed combination showed an additive result when a diminished result would have been expected. See MPEP 716.02. The test of obviousness is not express suggestion of the claimed invention in any or all of the references but rather what the references taken collectively would suggest to those of ordinary skill in the art presumed to be familiar with them." See In re Rosselet, 146 USPQ 183, 186 (CCPA 1965). In response to applicantās arguments against the references individually, one cannot show non-obviousness by attacking references individually where the rejections are based on combination of references. See MPEP 2145. "There is no requirement (under 35 USC 103(a)) that the prior art contain an express suggestion to combine known elements to achieve the claimed invention. Rather, the suggestion to combine may come from the prior art, as filtered through the knowledge of one skilled in the art." Motorola, Inc. v. Interdiqital Tech. Corp., 43 USPQ2d 1481, 1489 (Fed. Cir. 1997). An obviousness determination is not the result of a rigid formula disassociated from the consideration of the facts of a case. Indeed, the common sense of those skilled in the art demonstrates why some combinations would have been obvious where others would not. See KSR Int'l Co. v. Teleflex Inc., 550 U.S., 2007 U.S. LEXIS 4745, 2007 WL 1237837, at *12 (2007) ("The combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results."). Here, given that the agonist anti-CD40 antibody has been shown to directly inhibit tumors, rescue the function of antigen-presenting cells, and triggers active immune response against tumor-associated antigens and given that blocking FcγRIIb on antigen presenting cells including B cell and dendritic cells leads to enhanced tumor-specific T cells, and since amino acid substitution S267E in the Fc region of an IgG antibody can enhance binding to FcγRIIb over ninety fold as compared to the unmodified Fc region, an ordinary skill in the art would have been motivated to combine the teachings of the references to make amino acid substitution S267E in the Fc region of the anti-CD40 antibody following detailed methodology disclosed in either Chu et al. or Dahiyat et al. with reasonable expectation of success. The modify anti-CD40 antibody would be expected to have enhanced binding to FcγRIIb and activate antigen presenting cells including B cell or dendritic cell (both express FcγRIIb) and thereby would be expected to be suitable for in vitro or animal study for therapeutic uses. Therefore, applicantās arguments have not been found persuasive. 17. Claims 6-8 and 10 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Dahiyat et al. (US 2006/0121032) in view of de Goer de Herve et al. (Blood 15 October 2005, 106;8:2806-2814), Vonderheide et al. (Journal of Clinical Oncollogy March 1, 2007, 25;7:876-883) and Dhodapka et al. (PNAS February 22, 2005, 102;8:2910-2915) as applied to claims 1 and 3 above, and further in view of Bernett et al. (US 2008/0199471) and Zuk et al (US 4,281,061). The teachings of Dahiyat, de Goer de Herve, Vonderheide, and Dhodapka have been discussed, above. The reference teachings differ from the instant invention by not describing a pharmaceutical composition comprising the antibody and a chemotherapeutic agent including taxane, and a kit. Bernett et al. teach anti-CD40 antibodies comprises at least one modification in the Fc region that alters the affinity to FcγR or altered effector functions (e.g. see [0062]). Bernett et al. further teach that the anti-CD40 antibodies can be formulated in a pharmaceutical composition (e.g. see [0236]) or as immunoliposomes for enhanced circulation time (e.g. see [0237]) which is a sustained release formulation. Bernett et al. further teach that the antibody can be administered together with taxane (e.g. see [0260]). Zuk et al. teach that reagents for an immunoassay can be provided as kits as a matter of convenience and to optimize the sensitivity of the assay in the range of interest (col 22, line 62 - col 23, line 4). It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to formulate the anti-CD40 antibodies in sustained release formulation and combine with a chemotherapeutic agent such as taxane and further include the necessary reagents to perform the immunodiagnostic assay in a kit format for the convenience and economy of the user. One would have been motivated to assemble the reagents in a kit format to standardize the reagents for the optimization the assay for use in a clinical diagnostic laboratory or physician's office with a reasonable expectation of success. 18. 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 āright to excludeā granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims 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); 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 nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b). The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13. The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) 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 www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer. 19. Claims 1-5 are rejected on the ground of nonstatutory double patenting as being unpatentable over: Claims 1-8 of US 9,657,106 (the ā106 Patent, claims are drawn to a protein comprising an Fc variant comprising amino acid substitution S267E); Claims 1-3 of US 9,902,773 (the ā773 Patent, claims are drawn to a protein comprising an Fc variant comprising amino acid substitutions S267E and L328F); Claims 1-3 of US 9,914,778 (the ā778 Patent, claims are drawn to a protein comprising an Fc variant comprising amino acid substitutions G236N and S267E); and Claim 1 of US 9,260,523 (the ā523 Patent, claim is drawn to a method of activating at least one B cell by contacting the cell with an immunoglobulin comprising a Fv that binds CD40 and an Fc comprising S267E and L328F substitutions, all in view of Vonderheide et al. (Journal of Clinical Oncology, March 1, 2007, 25;7:876-883) for the reasons of record. Applicant requests that the rejections be held abeyance. As such, the rejections are maintained for the reasons of record. 20. No claim is allowed. 21. Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHUN DAHLE whose telephone number is (571)272-8142. The examiner can normally be reached Mon-Fri 6:30am-4:00pm. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. If attempts to reach the examiner by telephone are unsuccessful, the examinerās supervisor, Misook Yu can be reached at 571-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /CHUN W DAHLE/Primary Examiner, Art Unit 1641