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 .
The amendment filed 13 March 2026 is acknowledged and has been entered.
Status of the Claims
Claims 2 and 3 have been cancelled.
Claims 6-14 have been withdrawn.
New dependent claim 15 has been submitted.
Claim Rejections - 35 USC § 112
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 1, 4, 5 and 15 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 1 is rendered vague and indefinite by the phrase “wherein the injectable composition is administered together with stem cells”. It is not clear how this language is meant to limit the claim, which is directed to a method of manufacturing an injectable composition, not its method of use. Therefore, any administration (or dosage as in new claim 15) does not appear to fit into a method of making. That is – Does the method include a step of administration? Is there a step in the method of adding stem cells to the injectable composition, such that the injectable composition contains the supernatant collected after centrifugation of the solution along with the stem cells?
All other claims depend directly or indirectly from rejected claims and are, therefore, also rejected under U.S.C. 112, second paragraph, for the reasons set forth above.
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.
Claims 1 and 4-5 are rejected under 35 U.S.C. 103 as being unpatentable over KR 10-2018-0005130A (Kangstem) and Rothrauff et al. (2017). [cited in IDS filed by Applicant 8/30/2023]
Kangstem discloses an injectable composition containing pig-derived acellular lysates and stem cells for preventing or treating osteoarthritis (see entire document, including e.g, claims 1, 4, 10, paragraphs [0001], [0013], [0055], [0071] and [0179].
Rothruauff et al. beneficially teach tissue-specific bioactivity of soluble tendon-derived and cartilage derived extracellular matrices on adult mesenchymal stem cells and includes the steps of: solubilizing extracellular matrices by reaction at 37oC with enzymes for an hour and collecting the supernatant obtained by centrifuging the aqueous solution to prepare a composition for tissue specific stem cell differentiation. Sterilization is carried out by a syringe filter during the process of preparing extracellular matrices (see entire document, including e.g., Abstract, page 2 right column, page 3 left column, page 3 right column).
It would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the instant Application to employ pig-derived CAM in treating osteoarthritis as evidenced by the cited prior art and the plethora of attached references as well as those recited in the IDS filed by Applicant. It would have been well within the purview of the skilled practitioner to solubilize any the number of CAM powders known in the art with a solvent to prepare an injectable composition. Injectable cartilage acellular matrix compositions were known in the art before the present application. There are no hints in the prior art that a precise temperature range has any particular significance, but a solubilization treatment at 37°C appears to be common.
In KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398 (2007), emphasized a flexible approach to the obviousness question, stating that the analysis under 35 U.S.C. § 103 "need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ." Id. at 418; see also id. at 421 ("A person of ordinary skill is... a person of ordinary creativity, not an automaton."). Furthermore, in KSR, the Supreme Court indicated that the obviousness analysis should consider the “background knowledge possessed by a person having ordinary skill in the art.” KSR Int’l Co. v. Teleflex, Inc., 550 U.S. 398 (2007). Under KSR, information deemed within PHOSITA’s general knowledge is more powerful than that found buried in a prior art reference because we assume that PHOSITA would consider using their general knowledge in combination with the prior art — even absent any express motivation to do so. Under 35 U.S.C. § 103, the obviousness inquiry turns not only on the prior art, but whether “the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious . . . to a person having ordinary skill in the art to which the claimed invention pertains.” 35 U.S.C. § 103. Regardless of the tribunal, the inquiry into whether any “differences” between the invention and the prior art would have rendered the invention obvious to a skilled artisan necessarily depends on such artisan’s knowledge.
The adjustment of particular conventional working conditions (e.g., determining the optimal variables in preparing the CAM for injection, such as temperature, duration of solubilization and to employ sterilization techniques for preparing an injectable) is deemed merely a matter of judicious selection and routine optimization which is well within the purview of the skilled artisan. See e.g., MPEP2144.05.
Accordingly, the instant claims, in where no unexpected results are observed (e.g., evidence of criticality of the experimental variables recited in the method), would have been obvious to one of ordinary skill having the above cited references before him/her.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the 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.
Claims 1, 4, 5 and 15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 15-19 of U.S. Patent Application No. 18/333,812.
Although the claims at issue are not identical, they are not patentably distinct from each other because both are drawn to methods of manufacturing an injectable composition for preventing or treating osteoarthritis, the method comprising the steps of (a) solubilizing a composition including an animal CAM by stirring the composition at a temperature higher than 30°C and lower than 55°C;(b) preparing an injectable composition by centrifuging the aqueous solution prepared in the step (a) and collecting a solution. Hence, for all the reasons stated above in the obviousness rejection, it would have been well within the purview of the skilled artisan to optimize the variables such as temperature to obtain a preferred range of 30 to 50oC as taught by the claims of the pending Application. In addition, please note that the instant claims encompass and/or are encompassed by the "812 claims.
Response to Arguments
Applicant’s amendments/arguments, with respect to the 35 USC 112(b) rejections have been fully considered and are persuasive. The 35 USC 112(b) rejections of the previous Office action has been withdrawn. However, Applicant’s amendments have introduced new indefiniteness into the claimed method.
Applicant's arguments filed with respect to the 35 USC 103 rejection have been fully considered but they are not persuasive.
Applicant asserts that Kangstem discloses an injectable composition containing pig-derived acellular lysates and stem cells for preventing or treating osteoarthritis but does not disclose the specific condition of the solubilization step of amended Claim 1, which is performed at a temperature of 33°C to 37°C for 3 hours or more but less than 24 hours. Furthermore, the Applicant points to the fact that even within the single document Rothrauff, various distinct temperature and time conditions are used rather than commonly adopting 37°C and given the vast possible solubilization conditions, it would not have been possible to narrow the temperature and time to the specific ranges recited in amended Claim 1 without hindsight bias.
However “[a]ny judgment on obviousness is in a sense necessarily a reconstruction based on hindsight reasoning, but so long as it takes into account only knowledge which was within the level of ordinary skill in the art at the time the claimed invention was made and does not include knowledge gleaned only from applicant's disclosure, such as reconstruction is proper." In re McLaughlin, 443 F.2d 1392, 1395, 170 USPQ 209, 212 (CCPA 1971). MPEP 2145.X.A.
Indeed, the fact that many different reaction conditions and temperature are disclosed in the specification would indicate such conditions are meant to be routinely optimized as stated previously.
Applicant further asserts that, by specifying the particular solubilization conditions, amended Claim 1 achieves the unexpected result of satisfying (i) injectable viscosity and physical properties, (ii) retention of active ingredients such as collagen, and (iii) induction of chondrocyte differentiation of stem cells. For instance, Example 2, [0081]-[0082], of the present specification demonstrates that the injectable formulation is successfully formed specifically within the temperature range of 33°C to 37°C. In Example 4, [0089], it was confirmed that the collagen content decreased when the solubilization time was 24 hours or more and the solubilization temperature was 55°C or higher" (Emphasis added). In Example 5, [0091], the injectable composition solubilized at 37°C for 6 hours was capable of inducing chondrocyte differentiation of stem cells, whereas compositions solubilized at 37°C for 24 hours, 55°C for 6 hours, or 55°C for 24 hours failed to induce chondrocyte differentiation of stem cells.
However, with respect to such unexpected results, please note that in KSR, the Court also reaffirmed that evidence of unexpected results may overcome an examiner's prima facie case of obviousness. KSR, 550 U.S. at 416 ("The fact that the elements worked together in an unexpected and fruitful manner supported the conclusion that Adams' design was not obvious to those skilled in the art" - discussing United States v. Adams, 383 U.S. 39). However, "any superior property must be unexpected to be considered as evidence of non-obviousness." Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1371 (Fed. Cir. 2007). Thus, "[m]ere improvement in properties does not always suffice to show unexpected results ....[W]hen an applicant demonstrates substantially improved results.., and states that the results were unexpected, this should suffice to establish unexpected results in the absence of evidence to the contrary." In re Soni, 54 F.3d 746, 751 (Fed. Cir. 1995). Moreover, in order to establish unexpected results for claimed invention, objective evidence of non-obviousness must be commensurate in scope with the claims which the evidence is offered to support. In re Greenfield, 571 F.2d 1185, 1189 (CCPA 1978). Please also note that "the discovery of an optimum value of a variable in a known process is usually obvious." Pfizer v. Apotex, 480 F.3d at 1368. The rationale for determining the optimal parameters for prior art result effective variables "flows from the 'normal desire of scientists or artisans to improve upon what is already generally known.'" Id. (quoting In re Peterson, 315 F.3d 1325, 1330 (Fed. Cir. 2003)).
In order to accord substantial weight to secondary considerations in an obviousness analysis, “the evidence of secondary considerations must have a ‘nexus’ to the claims, i.e., there must be ‘a legally and factually sufficient connection’ between the evidence and the patented invention.” Henny Penny Corp. v. Frymaster LLC, 938 F.3d 1324, 1332 (Fed. Cir. 2019) (quoting Demaco Corp. v. F. Von Langsdorff Licensing Ltd., 851 F.2d 1387, 1392 (Fed. Cir. 1988)). “The patentee bears the burden of showing that a nexus exists.” WMS Gaming Inc. v. Int’l Game Tech., 184 F.3d 1339, 1359 (Fed. Cir. 1999). “To determine whether the patentee has met that burden, we consider the correspondence between the objective evidence and the claim scope.” Henny Penny, 938 F.3d at 1332.
Applicant's amendments/arguments filed with respect to the ODP rejection have been fully considered but they are not persuasive.
Applicant asserts that claims 1 to 5 are patentably distinct from U.S. Patent Application No. 18/333,812, because amended Claims 1 to 5 are directed to methods of manufacturing an injectable composition comprising a high content of collagen and having the ability to induce chondrocyte differentiation of stem cells, whereas U.S. Patent Application No. 18/333,812 is more focused on preparing the "injectable formulation" using CAM as a raw material. As such, the claims as amended avoid nonstatutory double patenting.
This is unpersuasive, firstly because the claims under examination are 1, 4, 5 and 15, not “claim 1-5”. Secondly, nowhere in the claimed method is “a high content of collagen and having the ability to induce chondrocyte differentiation of stem cells” recited. Both are methods of making an injectable formulation. In addition, please note that the instant claims encompass and/or are encompassed by the ‘812 claims.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RUSSELL G FIEBIG whose telephone number is (571)270-5366. The examiner can normally be reached M-F 8-4.
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/RUSSELL G FIEBIG/ Examiner, Art Unit 1655
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