DETAILED ACTION
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 .
Status of the Claims
Claims 1-4 are pending, presented for examination, and rejected as set forth below.
Claim Interpretation
Applicants claims are directed to methods of exposing a mineralized collagen glycosaminoglycan (MCGAG) scaffold with a solution containing each of EDC and N-hydroxysuccinimide (NHS) to form a crosslinked scaffold, as well as a solution containing a crosslinking agent and an osteoprotegerin (OPG or an OPG fragment. Claim 2 indicates “the crosslinking agent” is SPDP, and Claim 3 that “the crosslinking agent” is PEGylated-SPDP. Claim 4 indicates the solution is to include phosphate-buffered saline.
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 2 and 3 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.
Each of Claims 2 and 3 purport to limit “the crosslinking agent” of Claim 1. However, Claim 1 recites, once explicitly and once by implication, two distinct phases where a crosslinking agent is used. Neither Claim 2 nor Claim 3 specify whether “the crosslinking agent” being further limited is one employed in the making of the crosslinked MCGAG scaffold, or where the OPG is covalently bound to the crosslinked MCGAG scaffold. When a claim is amenable to two or more plausible constructions, applicant is required to amend the claim to more precisely define the metes and bounds of the claimed invention, or the claim remains indefinite under § 112. Ex parte Miyazaki, 89 USPQ2d 1207 (BPAI 2008) (expanded panel). For purposes of compact prosecution, the “crosslinking agent” limited by each of Claims 2 and 3 will be considered to refer back to the explicitly enumerated “crosslinking agent” of the step where the OPG is covalently bound to the crosslinked MCGAG scaffold.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, 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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-4 are rejected under 35 U.S.C. 103 as being unpatentable over Harley (WO2019/194894), in view of Nataraj (U.S. PGPub. 2010/0266559), and Chung (U.S. PGPub. 2020/0140844).
Harley describes methods of forming a collagen glycosaminoglycan scaffold which may be mineralized by forming a mineralized scaffold, exposing the scaffold to a solution containing 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and N-hydroxysuccinamide, then contacting that scaffold with a solution containing osteoprotegerin (OPG) or a fragment thereof to produce a OPG-bound scaffold, with Harley indicating that phosphate buffered saline (PBS) may serve as the solution for the OPG. [0054; 0109; 0118; 0128-29]. More particularly, Harley describes a method whereby a mineralized collagen glycosaminoglycan (MCGAG) scaffold is combined with a PBS solution containing each of the 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and N-hydroxysuccinamide of the instant claims to provide a MCGAG scaffold. [0079; 0142-43]. Harley specifically indicates alternative MCGAG scaffolds are ones which, once formed, are sterilized and crosslinked, addressing the newly added language of Claim 1. [0133; 0142-43; 0182-83]. Harley indicates that OPG may be covalently bound to the MCGAG by additional crosslinking to the MCGAG scaffold. [0215].
Despite reciting processes including the formation of a crosslinked mineralized collagen glycosaminoglycan scaffold, the exposure of that scaffold to a PBS solution containing each of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and N-hydroxysuccinamide, then combining the MCGAG so treated to a solution combining PBS with an OPG to crosslink the OPG to the scaffold, Harley does not specifically indicate that a crosslinking agent, let alone any of the crosslinking agents specifically recited by each of Claims 2 and 3, may be used.
However, Nataraj indicates that biological implants may be conjugated with small peptides to provide biological activities to tissues where the implants are to be located, including peptides such as an osteogenic growth peptide. [0130-31]. Nataraj indicates that heterobifunctional reagents can be employed as the conjugating agent for crosslinking the small proteins to the implants, [0166], but fails to identify either of the SPDP or pegylated SPDP of the instant claims as suitable conjugating agents. However, Chung indicates that each of the SPDP and PEGylated SPDP of the present claims were at the time known to be useful agents for crosslinking proteins and protein fragments to polymeric carrier materials. [0032].
It would have been prima facie obvious to one of ordinary skill in the art at the time the instant application was filed to have used a heterobifunctional crosslinking agent to covalently attach a protein such as OPG to an implantable scaffold such as is described by the process of Harley. This is because Harley indicates that proteins such as OPG may be covalently crosslinked to a MCGAG scaffold, and that heterobifunctional crosslinking agents are taught by Nataraj as crosslinking agent suitable for covalently linking proteins including OPG to bioimplants. The use of SPDP or PEGylated SPDP as such a heterobifunctional crosslinking agent appears, by the teachings of Chung, little more than the selection of an element known in the art to be useful for the purpose for which it is being chosen; namely, the capacity to crosslink peptides to polymeric substrates for implantation. See KSR v. Teleflex, 127 S.Ct. 1727, 1740 (2007) (quoting Sakraida v. A.G. Pro, 425 U.S. 273, 282 (1976)) (indicating that “[w]hen a patent simply arranges old elements with each performing the same function it had been known to perform and yields no more than one would expect from such an arrangement, the combination is obvious.”); see also Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945)(holding that generally, it is prima facie obvious to select a known material for incorporation into a composition, based on its recognized suitability for its intended use).
Response to Arguments
Applicant’s arguments filed 12 August 2026 with respect to the rejections of claims 1-4 under 35 U.S.C. 112(a) and 35 U.S.C. 112(b) have been fully considered and are persuasive. Therefore, these previous rejection have been withdrawn. However, in view of the amendments to the claims provided by applicants in their response of 12 August, the above new rejection of Claims 2 and 3 under 35 U.S.C. 112(b) has been entered.
Applicant's arguments filed 12 August 2026 with respect to the rejections of claims 1-4 under 35 U.S.C. 103 have been fully considered but they are not persuasive.
Applicants assert that the one-step process described by Harley, specifically in paragraphs [0129; 0213-15], represent a one step process whereby the crosslinking of the scaffold and covalent binding via crosslinker are performed simultaneously, distinct from the two-step process of the present claims. Even if that represented the totality of what Harley conveys to the skilled artisan, a position the Examiner does not concede, such a modification of the prior art would not, without more, distinguish the present claims from the prior art. This is because it has long been held that the selection of any order of performing process steps is prima facie obvious in the absence of new or unexpected results. In re Burhans, 154 F.2d 690, 69 USPQ 330 (CCPA 1946). Here, the record lacks such evidence to distinguish a two-step from one step process. As a result, without going further into what Harley teaches when considered as a whole, applicants arguments on this point are unpersuasive.
However, Harley goes further than the limited portion applicants attempt to rely on in their response. That is because it has long been established that art is art, not only for what it expressly teaches, but also for what it would reasonably suggest to the skilled artisan, including alternative or non-preferred embodiments. Merck & Co. v. Biocraft Laboratories, 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); see also In re Boe, 355 F.2d 961, 148 USPQ 507 (C.C.P.A 1966), In re Chapman, 357 F.2d 418, 148 USPQ 711 (C.C.P.A. 1966) (establishing that a reference is not limited to its working examples, but must be evaluated for what it teaches those of ordinary skill in the art). As set forth above in response to applicants amendments to the claims, Harley describes crosslinking MCGAG scaffolds to be used in the invention in the absence of OPG. [0133; 0142-43; 0182-83]. Hurley indicates that
Although the present invention has been specifically disclosed by certain aspects, embodiments, refinements and optional features, modification, improvement and variation of such aspects, embodiments, and optional features can be resorted to by those skilled in the art, and that such modifications, improvements and variations are considered to be within the scope of this disclosure. [0219].
As such, applicants insistence that the single embodiment of OPG being covalently bound to a crosslinked MCGAG following the crosslinking of the MCGAG scaffold remains an obvious modification of the Hurley disclosure.
Applicants argument that the OPG of Nataraj is not the identical osteoprotegerin of the claims or the Hurley disclosure continues the error of conflating specific embodiments of a prior art reference for all that the art, considered as a whole, conveys to the skilled artisan. Nataraj conveys to the skilled artisan that the dividing line between small peptides and larger proteins including conjugate proteins and growth factors which may suitably be crosslinked to scaffolds using the methods and components described within is arbitrary. Nataraj [0130]. As there is nothing of the record establishing the inability of the skilled artisan to utilize the protein crosslinking reagents specifically taught by Nataraj as protein crosslinking reagents in the covalent crosslinking processes of the Hurley reference, the identity of the specific proteins recited by the Nataja reference amounts to a distinction without a true difference in terms of the knowledge each conveys to the skilled artisan concerning covalent attachment via crosslinking of peptides to MCGAG scaffolds.
Applicants assertion that their Strategy 1 attempts to fabricate the Harley one-step process failed to provide scaffolds possessing osteoclastic inhibitory effects is unpersuasive, as it has long been held that the failures of experimenters who have no interest in succeeding should not be accorded great weight. In re Michalek, 162 F.2d 229, 74 USPQ 107 (CCPA 1947); In re Reid, 179 F.2d 998, 84 USPQ 478 (CCPA 1950). Here, the provision of an osteoclastic inhibitory MCGAG scaffold is precisely what Hurley describes. Hurley [0007; 0140; 0180; 0209-11; 0218].
Applicants arguments that Chung fails to remedy the alleged deficiencies of Hurley and Nataraj is unpersuasive for the reasons set forth above. Applicants additional argument concerning the number of alternative crosslinkers recited by Chung is likewise unpersuasive, as it has long been held that it is well settled that it is a matter of obviousness for one of ordinary skill in the art to select a particular component from among many disclosed by the prior art as long as it is taught that the selection will result in the disclosed effect, even when the possible selections number 1200 or in the thousands. Merck & Co., Inc. v. Biocraft Labs., Inc., 874 F.2d 804, 807 (Fed. Cir. 1989); In re Corkill, 771 F.2d 1496, 1500 (Fed. Cir. 1985). That there are a number of crosslinking reagents available to crosslink proteins to medical implants fails to render the selection of any one of them a non-obvious choice.
For at least these reasons, applicants arguments are unpersuasive.
Conclusion
No Claims are allowable.
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 nonprovisional extension fee (37 CFR 1.17(a)) 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 SEAN M BASQUILL whose telephone number is (571)270-5862. The examiner can normally be reached Monday through Thursday, 5:30 AM to 4 PM.
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/SEAN M BASQUILL/Primary Examiner, Art Unit 1614
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