DETAILED ACTION
The present application is a national stage entry of PCT/CN2022/071012, filed 10 January 2022, which claims priority to US Provisional Application No. 63/135,018, filed 08 January 2021.
The preliminary amendment filed 28 June 2023 is acknowledged. Claims 1-20 are pending in the current application. Claims 12-20 are withdrawn as being drawn to a non-elected invention, see below. Claims 1-11 are examined on the merits herein.
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant’s election of Group I, claims 1-11 in the reply filed on 21 May 2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 12-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Applicant’s election of chondroitin sulfate as a First species of GAG component; aminated HA as a Second species of ECM component; TAEA as a Third species of amination reagent; ‘bottlebrush’ like structure as a Fourth species of form, in the reply filed on 21 May 2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
To expedite prosecution, the Second species of ECM component has been expanded to include aminated collagen, and the Third species of amination reagent has been expanded to include EDA.
Claims 12-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The 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.
Claims 7-9 are 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.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 8 recites the broad recitation “ratio of from 1:1 to 100:1, from 1:1 to 50:1”, and the claim also recites “preferably 5:1 or 27:1” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claims 7 and 9 similarly recite “preferably” language, and is similarly held indefinite.
Claim Rejections - 35 USC § 102
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 (i.e., changing from AIA to pre-AIA ) 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 the appropriate paragraphs of 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 –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1-5 and 8-10 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Choy et al. (Acta Biomaterialia, 2013, vol. 9, pp. 4661-4672, cited in IDS submitted 07 August 2023).
Choy et al. teach preparing glycosaminoglycan (GAG)-rich collagen scaffolds for tissue engineering (abstract). They found modifying collagen with an amine altered the net charge of the collagen, which allowed it to retain over 40% GAG upon co-precipitation. They found modifying collagen with an amine increased the GAG/hydroxyproline ratio in the co-precipitate to >4.5:1, approaching that of native nucleus pulposus (abstract, Fig. 1). The modified scaffold promoted cell proliferation of human mesenchymal stem cells and showed >95% cell viability. The precipitate showed 60% GAG retention after 8 days (p.4669, first para).
The aminated collagen was prepared by reacting collagen with ethylenediamine (EDA), (p.4662, 2.4). A co-precipitate of collagen and GAG was prepared by dissolving chondroitin-6-suflate from shark cartilage in acetic acid (p.4662, 2.1). Type I collagen (unmodified or chemically modified) was mixed with excess GAG. The GAG was negatively charged (p.4667, 4. Discussion). Amination with ethylenediamine makes the collagen (i.e. the ECM) carry a positive amino charge (p.4667, 4.1). Carrying a positive charge allows collagen to react with more GAGs (4.1). This method avoids harsh crosslinking conditions, and increases GAG retention (1.Introduction, and section 4.1). Choy et al. teach the prepared scaffold can be used for regeneration of GAG-rich tissues such as intervertebral disc (5. Conclusion).
The recitation “wherein the precipitate is in the form of small nano-sized ‘beads’ like structure, micro-scale aggregation, or ‘bottlebrush’ like structure” in claim 10 is a latent property of the precipitate. As evidenced by the present Specification, “aCol(EDA)-GAG and aCol(TAEA)-GAG showed nano-size (20-40 nm) ‘beads’ like structure” (see paragraph [0108] of the published application).
Thus, the disclosure of Choy et al. anticipates claims 1-5 and 8-10 of the present application.
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 (i.e., changing from AIA to pre-AIA ) 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.
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.
Claim(s) 1-5 and 8-11 are rejected under 35 U.S.C. 103 as being unpatentable over Choy et al. (Acta Biomaterialia, 2013, vol. 9, pp. 4661-4672, cited in IDS submitted 07 August 2023).
Choy et al. teach as discussed above.
Choy et al. do not expressly a GAG:HYP ratio of 5:1 (present claim 11).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to optimize precipitation conditions to increase the GAG:HYP ratio, because naturally occurring tissue like native nucleus pulposus has a high GAG to HYP ratio. The ordinary artisan would have had a reasonable expectation of success, because Choy et al. teach modifying the ECM was an effective method for modifying the GAG:HYP ratio, and already showed they were able to attain nearly 5:1 ratio.
Thus, the claimed invention as a whole is prima facie obvious over the combined teaching of the prior art.
Claim(s) 6 and 7 are rejected under 35 U.S.C. 103 as being unpatentable over Choy et al. as applied to claims 1-5 and 8-11 above, and further in view of Shen et al. (Orthopedic Research and Reviews, 2010, vol. 2, pp.17-26, cited in PTO-892).
Choy et al. teach as discussed above.
Choy et al. do not expressly disclose wherein the extracellular matrix component comprises aminated hyaluronic acid (present claim 6).
Shen et al. teach HA is a component of extracellular matrix in human tissue, and carries a highly negative charge (abstract). HA-based scaffolds have been prepared for intervertebral disc regeneration (IVD), including a gelatin/chondroitin-6-sulfate/HA tri-copolymer, and a cross-linked collagen-HA scaffold (p.22). These scaffolds preserved nucleus pulposus (NP) cells, preserved their viability, proliferation, promoted matrix synthesis, enhanced the production of proteoglycan and type II collagen in the ECM, and induced re-differentiation of human NP cells. The crosslinked collagen-HA scaffold retained sulfated GAG. HA has been shown to have promise in in vitro and in vivo animal models for regenerating IVD (p.22-23, bridging para). Shen et al. teach HA has shown intra-inflammatory effects when injected intradiscally, and has therapeutic potential as a cell carrier for disc regeneration (p.22).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the CS/aminated collagen composition of Choy et al. to include hyaluronic acid.
Starting from Choy et al., the ordinary artisan would have been motivated to modify the CS/aminated collagen composition of Choy et al. to include hyaluronic acid, because in the same field of endeavor of preparing compositions for tissue engineering for IVD regeneration, Shen et al. teach HA has shown intra-inflammatory effects when injected intradiscally, and has therapeutic potential as a cell carrier for disc regeneration.
The ordinary artisan would have had a reasonable expectation of success, because Shen et al. teach scaffolds for IVD comprising HA in combination with CS, and HA in combination with collagen were known before the effective filing date.
Since HA naturally carries a negative charge, one having ordinary skill in the art would have been motivated to modify HA to carry a positive charge, like Choy et al. did with collagen, so that it will also form an electrostatic complex with negatively charged CS. As taught by Choy et al., electrostatic complexation between GAG and ECM materials avoids harsh crosslinking conditions. Since HA is also an ECM material, the ordinary artisan would have been motivated to substitute collagen with HA, or include it in combination with collagen for complexation and retention of GAG.
The recitation “wherein the precipitate is in the form of small nano-sized ‘beads’ like structure, micro-scale aggregation, or ‘bottlebrush’ like structure” in claim 10 is a latent property of the precipitate. As evidenced by the present Specification, “aCol(EDA)-GAG and aCol(TAEA)-GAG showed nano-size (20-40 nm) ‘beads’ like structure” (see paragraph [0108] of the published application).
Thus, the claimed invention as a whole is prima facie obvious over the combined teaching of the prior art.
Claim(s) 7 is rejected under 35 U.S.C. 103 as being unpatentable over Choy et al. and Shen et al. as applied to claims 1-11 above, and further in view of Rhee et al. (CA 2,165,728, cited in PTO-892).
Choy et al. teach as discussed above.
Choy et al. do not expressly disclose tris(2-aminoethyl)amine (present claim 7).
Shen et al. teach as discussed above.
Rhee et al. teach polyacids can be chemically modified with a polyamine, wherein the polyamine includes ethylenediamine (EDA), or tris(2-aminoethyl)amine (TREN) from a small list of polyamines (p.18:10-19).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute EDA of Choy et al. with TREN, because they are recognized as alternative polyamines for use in modifying polyacids. The ordinary artisan would have had a reasonable expectation of success, because collagen and hyaluronic acid both carry carboxylic acid moieties, and collagen has successfully been modified with EDA.
Thus, the claimed invention as a whole is prima facie obvious over the combined teaching of the prior art.
Conclusion
In view of the rejections to the pending claims set forth above, no claim is allowed.
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/BAHAR CRAIGO/
Primary Examiner
Art Unit 1699
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