Patent Application 16086081 Rejection Details

Title: COMPOSITION FOR TREATING INTERVERTEBRAL DISC

Application Information

Invention Title: COMPOSITION FOR TREATING INTERVERTEBRAL DISC
Application Number: 16086081
Submission Date: 2025-04-07T00:00:00.000Z
Effective Filing Date: 2018-09-18T00:00:00.000Z
Filing Date: 2018-09-18T00:00:00.000Z
National Class: 424
National Sub-Class: 423000
Examiner Employee Number: 84056
Art Unit: 1611
Tech Center: 1600

Rejection Summary

102 Rejections: 0
103 Rejections: 1

Cited Patents

The following patents were cited in the rejection:

US 0189231🔗

Office Action Text

DETAILED ACTION
Status of Application
The Examiner acknowledges receipt of the arguments filed on 12/20/2024.
Claims 41-55 and 58-67 are presented for examination on the merits. The following rejections are made.

Response to Applicants’ Arguments
Applicant’s arguments filed 12/20/2024 regarding the rejection of claims 41-55 and 58-67 made by the Examiner under 35 USC 103 over Lewis (J Biomed Mater Res B Appl Biomater, 2012, 100(6), 1702-1720) in view of Kalaf et al. (Mater Sci Eng C Mater Biol Appl, 2016, 63, 198-210), Iwasaki et al. (US 2013/0189231), Wang et al. (Tissue Engineering, 20(5), 2014, 908-920) and Meakin et al. (J Clin Biomech, 2001, 16, 560-565) have been fully considered but they are not found persuasive and is MAINTAINED for the reasons of record in the office action mailed on 9/20/2024.
In regards to the 103 rejection, Applicant asserts the following:
A) Iwasaki does not teach or suggest the mechanical properties of an alginate composition and Meakin does not teach the use of their polymer materials as an intervertebral disc.
In response to A, the material of the prior art possesses a Young’s modulus of 8 (see [0211]) whereas nuclear pulposus themselves have a Young’s modulus of between 0.2-40 (see page 565 of Meakin et al., J Clinical Biomechanics, 2001, 560-565). It is taught that a modulus within this band does not exhibit significant inward bulging which is a desired outcome of the repairing/replacing nuclear pulposus. The alginate material of the prior art possesses the mechanical properties known to be possessed by nuclear pulposus and so would have the material mechanics of the native tissue.
Regarding Meakin not teaching ‘the use of their polymer materials as an intervertebral disc’ is not persuasive. This feature is described by the other references provided by the rejection. Meakin is provided to show that nuclear pulposus are to have a Young’s modulus of between 0.2-40 which the material used by the prior art exhibits. So, although Meakin does not teach or describe using/applying crosslinked alginate as a nuclear pulposus, it provides data that supports the expectation the use of the alginate material as a nuclear pulposus would be successful.

Maintained Rejections, of Record
Claim Rejections - 35 USC § 103
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.
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, 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.

Claims 41-55 and 58-67 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lewis (J Biomed Mater Res B Appl Biomater, 2012, 100(6), 1702-1720; of record) in view of Kalaf et al. (Mater Sci Eng C Mater Biol Appl, 2016, 63, 198-210; of record), Iwasaki et al. (US 2013/0189231; of record), Wang et al. (Tissue Engineering, 20(5), 2014, 908-920; of record) and Meakin et al. (J Clin Biomech, 2001, 16, 560-565; of record).
Lewis teaches degenerative disc disease is implicated in the pathogenesis of many painful conditions of the back and that a surgical option is replacement or regeneration/repair of the nucleus pulposus (see abstract).
Lewis teaches that space created by removal of the degenerated nucleus pulposus (i.e. a defective site in a nucleus pulposus of the intervertebral disc) allows for the placement of a device, which can include in situ curable polymers (i.e. a composition to fill the defective site, see page 1703). Lewis teaches that alginates are biomaterials used for scaffolds for nucleus pulposus (see page 1710). Lewis teaches that an amidic derivative of alginate was used to form a hydrogel by crosslinking it with 1,3 diaminopropane, which swelled up to 250% in volume, a value that is similar to that for a normal human lumbar nucleus pulposus (see page 1709). Lewis teaches that the behavior of the hydrogel was very similar to that of normal human lumbar nucleus pulposus and that the hydrogel behaved more like a solid than a fluid (see page 1709).
Lewis fails to teach the alginate polymer as being applied to a defective site in a nucleus pulposus of the intervertebral disc. Lewis fails to teach a low endotoxin monovalent metal salt of alginic acid, and allowing a solid gel to form from a first portion of the composition after the applying, such that a second portion, which is other than the first portion, of the composition remains in the sol state. Lewis fails to teach a second portion, which is other than the first portion, of the composition remains in the sol state.
Wang describes a crosslinked alginate matrix for nucleus pulposus tissue engineering wherein the alginate material is applied (injected) in to the nuclear pulposus of rabbit intervertebral disc (see pages 909-910). Wang teaches that their alginate material is suitable for carrying and delivering stem cells to target biological locations, e.g. nuclear pulposus, so as to treat disc degeneration. Thus, it would have been obvious to apply the alginate materials of Lewis to a nuclear pulposus with a reasonable expectation for success in treating a degeneration and/or injury to an intervertebral disc as such was previously described by the prior art. Combining prior art elements according to known method to yield predictable results is indicia of obviousness. See MPEP 2143(I)(A).
Kalaf teaches an injectable, cellularized alginate-based nucleus pulposus that restores disc function (see abstract). Kalaf teaches that the alginate gel has tailorable rates of gelation to improve functionality and examines CaCO3:glucono-6- lactone (GDL), with 10% CaCl2 as the control crosslinker (see abstract). Kalaf teaches that alternatives to highly-invasive surgical procedures for lower back pain caused by severe intervertebral disc (IVD) degeneration include minimally-invasive injections into the nucleus pulposus (see page 198). Kalaf teaches an injectable the creation of uniform alginate macroblock geometries is quite difficult as the boundary of the alginate is tightly and rapidly bound upon contact with the crosslinking solution and that alginate provides controlled gelation (see page 198).
lwasaki teaches a composition for regenerating cartilage or treating a cartilage disease (see abstract) which is found in intervertebral discs (see [0068]). lwasaki teaches that the composition contains a monovalent metal salt of alginic acid for which the endotoxin level thereof has been lowered to an extent that does not substantially induce inflammation or fever (i.e. a low endotoxin monovalent metal salt of alginic acid, see abstract). lwasaki teaches that the composition is injected into a joint in a liquid state for the repair of cartilage at a cartilage injury lesion, including disc injury (see [0031]).
Iwasaki teaches that the composition has gel curability as a result of being contacted with Ca ions at the affected area (see [0277]). lwasaki teaches that the composition is injected into a joint in a liquid state (i.e. a sol, see [0031]). Iwasaki teaches that the composition can be applied with a syringe (see [0070]) and teaches that applying a solution of a divalent or more metal ion to the surface of the composition with a syringe or sprayer and that the crosslinking agent may be applied to the surface of the composition of the present invention either after or simultaneous to the application of the composition (see [0116)]).
Regarding claim 41, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to utilize a liquid (i.e. a sol) monovalent metal salt of alginic acid for which the endotoxin level thereof has been lowered to an extent that does not substantially induce inflammation or fever as taught by lwasaki in the method of Lewis. One would be motivated to do so with a reasonable expectation of success as Lewis teaches that an amidic derivative of alginate was used to form a hydrogel by crosslinking, and Kalaf teaches an injectable, cellularized alginate-based nucleus pulposus that restores disc function. Further, Iwasaki teaches that the composition can be used in intervertebral discs.
Regarding the limitation of a first portion as a solid gel and the second portion in the sol state, lwasaki teaches that the composition is injected into a joint in a liquid state (i.e. a Sol, see [0031]) and that a crosslinking solution of a divalent or more metal ion is applied to the surface of the composition with a syringe or sprayer, and that the crosslinking agent may be applied to the surface of the composition of the present invention either after or simultaneous to the application of the composition (see [0116]), which would form a “first potion” on the surface and a “second portion” under the first portion that is still liquid (i.e. a sol). Additionally, [0009] states that a graft composition which is exposed to metal crosslinking solution results in curing of the surface and [0114] teaches that the crosslinking agent is applied to the surface in order to gel the surface of the composition and solidify the surface. It is presumed that the emphasis on surface by Iwasaki suggests that only the surface is being reacted by the crosslinking agent rather than the whole of the composition. Such would read the structure suggested by instant claim 41.
Moreover, Iwasaki teaches that the Young’s modulus of their reacted composition is 8 (MPA presumably) (see [0211]). Meakin teaches that nucleus pulposus are desired to have a Young’s modulus of 0.2-40 MPa (see page 564). Thus, the resulting surface reacted composition would have the physical properties which would align with the physical properties exhibited by nuclear pulposus.
Regarding claim 42, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to utilize a liquid (i.e. the composition as fluidity when applied to the defective site) monovalent metal salt of alginic acid for which the endotoxin level thereof has been lowered to an extent that does not substantially induce inflammation or fever and then curing the composition by bringing a crosslinking agent into as taught by lwasaki in the method of Lewis. One would be motivated to do so with a reasonable expectation of success as Lewis teaches that an amidic derivative of alginate was used to form a hydrogel by crosslinking, and Kalaf teaches an injectable, cellularized alginate-based nucleus pulposus that restores disc function. Further, lwasaki teaches that the monovalent metal salt of alginic acid composition can be used in intervertebral discs.
Regarding claim 43, Lewis teaches degenerative disc disease, osteophytes in joints adjacent to the degenerated one, spinal stenosis, spondylotic myelopathy and radiculopathy, and disc herniation (see page 1702).
Regarding claims 44 and 45, Lewis teaches that space created by removal of the degenerated nucleus pulposus (i.e. a defective site in a nucleus pulposus of the intervertebral disc) allows for the placement of a device, which can include in situ curable polymers (i.e. a composition to fill the defective site, see page 1703).
Regarding claims 48 and 49, Lewis teaches that the height change can be increased by implantation (see page 1704).
Regarding claims 50 and 51, Lewis teaches that the degeneration of discs is due to a variety of factors including environmental factors, such as abnormal mechanical loading on the spine, driving and associated whole-body vibration, smoking, and changes due to aging (see page 1703).
Regarding claims 52-55, the prior art renders obvious the claimed method. A person of ordinary skill in the art would reasonably expect the use of the same composition with the same active steps to have the same result.
Regarding claims 58 and 59, lwasaki teaches the same composition as claimed for use in the instant method, including that that the sodium alginate has a weight average molecular weight of 500,000 (see [0025]). lwasaki teaches that the composition has a viscosity of 110-570 mPa:s (See Table 2).
Regarding claim 60, lwasaki teaches the preferable concentration of alginic acid in the solution of the monovalent metal ion of alginic acid is roughly 1 to 5% w/v (see [0098)).
Regarding claim 61, Iwasaki teaches a kit for regenerating cartilage or treating a cartilage disease which includes the composition for regenerating cartilage or treating a cartilage disease, a crosslinking agent, syringe, gel pipette, special-purpose filler, instructions and the like (see [0144]). lwasaki teaches a kit in which an alginic acid solution and a crosslinking agent are sealed in separate syringes and packaged together in a single pack (see [0144)).
Regarding claim 62, lwasaki teaches that the composition can be applied with an 18-27G needle (see [0130]). Iwasaki teaches that environmental changes such as a time difference, temperature difference or contact with calcium ion within the body effect gelation of the composition (see [0118]). One skilled in the art would be motivated to manipulate the time and temperature by routine experimentation, in order to optimize the desired gelation as Iwasaki teaches that that environmental changes such as a time difference, temperature difference or contact with calcium ion within the body effect gelation of the composition. Further, MPEP 2144.05 states that "[i]n the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art' a prima facie case of obviousness exists" quoting /n re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976). In the instant case the gauge of the needles taught in the prior art overlap on the instantly claimed gauge.
Regarding claim 63, Lewis teaches that an amidic derivative of alginate was used to form a hydrogel by crosslinking it with 1,3 diaminopropane, which swelled up to 250% in volume, a value that is similar to that for a normal human lumbar nucleus pulposus (i.e. compositions which do not contain a cell, see page 1709). Further, Iwasaki teaches compositions which do not contain cells (see [0185)).
Regarding claim 64, lwasaki teaches that the composition has gel curability as a result of being contacted with Ca ions at the affected area (see [0277)).
Regarding claim 65, lwasaki teaches compositions which contain cells (see [0185)).
Regarding claim 66, lwasaki teaches mesenchymal stem cells or bone marrow mesenchymal stromal cells (see [0105]). Iwasaki. teaches human transforming growth factor B3 (i.e. TGF-B, see [0170)).
Regarding claim 47, Lewis teaches degenerative disc disease, osteophytes in joints adjacent to the degenerated one, spinal stenosis, spondylotic myelopathy and radiculopathy, and disc herniation (see page 1702).
Therefore, the invention as a whole is prima facie obvious to one of ordinary skill in the art at the time the invention was filed, as evidenced by the references, especially in absence of evidence to the contrary.

Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KYLE A PURDY whose telephone number is (571)270-3504. The examiner can normally be reached from 9AM to 5PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Bethany Barham, can be reached on 571-272-6175. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KYLE A PURDY/Primary Examiner, Art Unit 1611