DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
This action is responsive to papers filed 11/04/2025.
Claim 2 has been amended. No claims have been newly canceled and claims 18-21 have been newly added.
Claims 2-11, 13-16, 18-21 are currently pending and have been examined on their merits.
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. 61/593415, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application.
The provisional ‘415 does not disclose a calcium solution having a calcium concentration of about 30 mM to about 90 mM as recited in independent claim 2.
Since the parent PCT/US2013/024467 does disclose this limitation claims 2-11, 13-16, 18-21 have been examined with the filing date of the PCT which is 02/01/2013.
Claim Interpretation
Applicant has added the following phrase to amended claim 2:
and wherein the composition, when administered in a therapeutically effective amount by direct injection to a knee joint of a subject that has or is at risk for developing arthritis at the joint, is effective to treat a torn, fractured, strained, bruised, or ruptured intra-articular tissue in the knee, wherein surgery has not been performed on the joint, and wherein surgery is not concurrently being performed on the joint.
This phrase is interpreted as an intended use of the claimed composition and given limited weight in that it requires that the composition be in a form suitable for such intended use. The method steps recited in this phrase do not limit the claimed composition.
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 pre-AIA 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, 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 negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) 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 under pre-AIA 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 pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 2-3, 5, 9-10, 13-16, 18-20 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Hoemann et al (US 7,148,209-from IDS filed 12/02/2022) in view of Murray et al (US 2009/0254104-from IDS filed 12/02/2022) and McKay (US 2010/0049322-from IDS filed 12/02/2022).
Regarding claims 2-3, 9, 15, 18-20, Hoemann teach compositions and methods for the repair of tissues (Title and abstract). The damaged tissue for treatment can be caused by arthritis (column 1 lines 50-55). The compositions administered are taught to advantageously contain collagen and blood components, specifically erythrocytes (red blood cells) and platelets (column 10, lines 42-48) and since GAG is only listed as an option, embodiments with little to no GAG are available (less than 5%). The inclusion of some amount of GAG, even less than 5%, as a secondary polymer ingredient would have been prima facie obvious as it is also taught to be a suitable additive.
“It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted). MPEP 2144.06
With regard to the concentrations of additives in the claimed and reference compositions, generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (MPEP 2144.05).
Potential administration is by injection into a body site where the mixture aids the repair, regeneration, reconstruction or bulking of tissues (column 9 lines 55-60) and a potential site of injection is to a knee (joint) and thus is deemed in a form suitable for Applicant’s claimed intended use (column 10 lines 64-65, column 13 lines 28-30, claim 5). Hoemann disclose wherein their compositions contain calcium and collagen as pro-coagulants (column 10 lines 50-52, columns 33-34 claims 17 and 37).
Hoemann teach wherein their polymer (collagen) is preferably initially dissolved or suspended in a buffer containing an inorganic salt, such as calcium (column 10, lines 20-32, column 33 claim 11) and wherein the blood component can comprise a pro- coagulant such as calcium and collagen to improve coagulation/solidification at the site of introduction (column 10 lines 50-55, column 33 claim 17).
Hoemann teach wherein the polymer could be in an aqueous solution or aqueous suspension (column 12 lines 64-67). This aqueous composition contains some amount of water.
The transitional phrase “consisting essentially of” limits the scope of a claim to the specified materials or steps and those that do not materially affect the basic and novel characteristic(s) of the claimed invention. A “consisting essentially of” claim occupies a middle ground between closed claims that are written in a consisting of format and fully open claims that are drafted in a comprising format. For the purposes of searching for and applying prior art under 35 U.S.C. 102 and 103, absent a clear indication in the specification or claims of what the basic and novel characteristics actually are, “consisting essentially of” will be construed as equivalent to “comprising.” See, MPEP 2111.03 and 2163.
Therefore, Hoemann is deemed to meet the requirement for containing collagen material, red blood cells, calcium solution, GAG and water.
Hoemann do not specifically teach wherein their collagen material was obtained from a dry powder form.
Murray ‘104 teach methods for the repair of damaged articular tissue with a collagen-based composition (page 4 para 70). Intra-articular injuries involved include injuries to the meniscus (knee), ligament and cartilage (page 4 para 71). Murray suggest that it is beneficial to lyophilize (dry) the collagen and store as a powder and then the collagen powder can be reconstituted (rehydrated) in a buffer solution prior to administration (page 7 para 106).
McKay teach compositions and methods that improve osteochondral repair (page 1 para 7). A suitable aqueous buffer for use with their methods includes calcium chloride at concentrations of 1 mM to about 100 mM (page 10 para 118).
One of ordinary skill in the art would have been motivated to lyophilize the collagen into a powder for the benefits of storage prior to use and then rehydrate that collagen powder with a calcium buffer solution with calcium at a concentration between 1mM and 100 mM (around 30-90 mM) in the method of Hoemann because Murray ‘104 and McKay teach that it is beneficial to do so with collagen intended for the repair of damaged joint tissue. One of ordinary skill in the art would have had a reasonable expectation of success because Hoemann also suggest the suspension of collagen in buffer with an inorganic salt such as calcium is desirable as well.
Regarding claims 2, 5 and 18, the ratio of calcium to collagen would be obtainable through routine optimization and experimentation using the values provided by McKay as the artisan of ordinary skill in the art would be motivated to obtain an injectable collagen composition with optimal therapeutic effects.
Regarding claim 10, Hoemann teach using autologous blood (column 9, lines 63-64).
Regarding claim 13, Hoemann teach wherein their polymer compositions can be in liquid form (column 14, lines 1-9, line 58).
Regarding claim 14, Hoemann teach wherein their polymer composition is in gel form (abstract, column 9 line 67- column 10 line 4).
Regarding claim 16, Hoemann teach that a suitable pH for the polymer (collagen) is between 6.5 and 7.8 (column 10 lines 39-40).
One of ordinary skill in the art would have been motivated to use a pH between 6.5 and 7.8 because Hoemann suggest that this is a suitable pH for a collagen polymer intended for administration to damaged cartilage tissue. in the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. (MPEP 2144.05) and thus the pH range disclosed by Hoemann renders obvious Applicant’s claimed range.
Murray ‘104 teach that the pH of the collagen material is preferably 7.2-7.6 or 7.4 (page 6 para 99 and page 7 para 107, para 109). Murray ‘104 teach that the collagen material is administered into a joint wound (page 7 para 109-110).
One of ordinary skill in the art would have been motivated to adjust the pH of the collagen material of Hoemann to a pH of 7.4 because Murray ‘104 indicate that this is a preferred pH for collagen material intended for therapeutic administration to a joint. One of ordinary skill in the art would have had a reasonable expectation of success because both Hoemann and Murray are administering collagen material to a joint for repair of damaged tissue and the pH of 7.4 falls within the pH range that Hoemann indicates is suitable for polymers such as collagen intended for tissue repair.
Therefore, the combined teachings of Hoemann et al, Murray ‘104 and McKay render obvious Applicant’s invention as claimed.
Claims 2-11, 13-16, 18-21 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Hoemann et al (US 7,148,209-from IDS filed 12/02/2022) in view of Murray et al (US 2009/0254104-from IDS filed 12/02/2022) and McKay (US 2010/0049322-from IDS filed 12/02/2022) as applied to claims 2-3, 5, 9-10, 13-16, 18-20 above, and further in view of Mansour (US 2002/0061842- from IDS filed 12/02/2022) and Abraham et al (US 5,993,844- from IDS filed 12/02/2022).
Regarding claims 2-11, 13-16, 18-21 Hoemann includes their polymer (collagen) in gel form (abstract, column 10 lines 1-2), but does not specifically teach wherein the collagen material is almost free or contains very low amounts of GAG (less than 5%), phospholipids, nucleic acids, and active pepsin.
Mansour teaches methods of sterilizing native collagen for pharmaceutical and medical use (abstract, page 2 para 25-27). Mansour teaches that collagen must be free of contamination (virus) when in medical use (page 1 para 6). Viral inactivation is also taught to inactivate any pepsin present as well (page 3 para 74). The neutralization of pepsin brings the pH to 6.8 to 7.4 (page 4 para 75) which renders a pH of 7.4 an obvious choice for a pharmaceutical collagen composition.
Abraham et al teach methods for the treatment of collagenous tissue to remove non-collagenous components such as cellular debris, lipids and nucleic acids (abstract and column 3 lines 39-52). The removal of non-collagenous structures present in native tissue is desired because these structures are believed to be antigenic and will elicit a chronic inflammatory response when implanted in a host (column 1 lines 56-60). Abraham’s method is taught to be improved over previous methods of preparing collagen with detergents, surfactants and enzymes (columns 1-3). Importantly, the bioremodelability of the tissue matrix is preserved as it is free of bound detergent residues that would adversely affect the bioremodelability of the collagen. Further the collagen is telopeptide collagen as the telopeptide regions remain intact as it has not undergone treatment or modification with enzymes during the cleaning process (column 3 lines 45-52). A preferred composition is essentially acellular with less than 5% glycoproteins (non-collagen extracellular matrix component), glycosaminoglycans, proteoglycans, lipids, non-collagenous proteins and nucleic acids (column 8 lines 42-48). The pH of the collagen material is preferably about 7.4 (column 8 lines 15-20).
One of ordinary skill in the art would have been motivated to use a collagen substantially free or very low amounts of cellular debris, all lipids including phospholipids and nucleic acids in the method of Hoemann because Abraham teach that such collagen is preferred for transplantation. One of ordinary skill in the art would have been motivated to use sterilized collagen in the method of Hoemann because Mansour teaches that collagen must be free of contamination (virus) when in medical use (page 1 para 6). One of ordinary skill in the art would have been motivated to use collagen that is almost free of active pepsin because Mansour indicates that this is beneficial as well. Any phospholipid, nucleic acid or active pepsin present would be so at only trace amounts as removing as much as possible would be desirable. One of ordinary skill in the art would be motivated to allow any GAG to be present in trace amounts or less than 5% as suggested is appropriate by Abraham. This would allow for a non-collagen extracellular matrix component to be present in trace amounts). One of ordinary skill in the art would have had a reasonable expectation of success because Hoemann, Mansour and Abraham are administering collagen material for repair of damaged tissue and Mansour describes methods for sterilization and viral inactivation suitable for use with collagen intended for medical use.
Therefore, the combined teachings of Hoemann et al, Murray ‘104, McKay, Mansour and Abraham et al render obvious Applicant’s invention as claimed.
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 2-11, 13-16, 18-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 11,484,578.
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the patent are drawn to a method of using the same claimed injectable composition for treating arthritis and thus anticipates the claims of the current invention.
Therefore, the claims of the patent anticipate the claims of the current application.
Response to Arguments
Applicant's arguments filed 11/04/2025 have been fully considered but they are not persuasive.
Applicant argues that the cited references fail to suggest a composition that is effective to treat a torn, fractured, strained, bruised or ruptured intra-articular tissue in the knee when administered by direct injection to a knee joint of a subject that has or is at risk for developing arthritis at the joint, wherein surgery has not been performed on the joint, and wherein surgery is not concurrently being performed on the joint as recited in present claim 2.
This is not found persuasive. The claimed invention is drawn to a composition and thus limitations drawn to the intended use of the claimed composition are only given limited weight in that they require that the composition be in a form suitable for such intended use.
Applicant argues that the Office’s position that a person of ordinary skill in the art would have looked to McKay as a starting point for the presently recited calcium concentration. Applicant asserts that because McKay discloses an osteochondral repair implant that includes a tissue scaffold and a biodegradable carrier wherein the growth factor can be supplied in a buffer to a portion of an implant does not translate to making an injectable composition that contains a solution having a particular concentration of calcium as recited in the present claims. Applicant asserts that the because McKay is so vastly different from an injectable composition that there is no reason that a person of ordinary skill in the art would have looked to McKay’s disclosure of a solid implant in order to determine how to generate an injectable composition containing collagen and calcium as recited in the present claims.
This is not found persuasive. The test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981).
The McKay reference is cited to demonstrate the concentration of buffering agents used in a buffer composition fall within Applicant’s claimed composition and thus provide a starting point for the optimization of calcium concentration used in a buffer as suggested by Hoemann and Murray. The concentration of a buffer is selected so that the solution can maintain a preferred pH and the concentration given is that of the buffering agent contained in the buffer (see JP 2011-504477A- page 11 as evidence of how buffer concentrations are interpreted).
The action is not relying on McKay for the teaching of the composition for the tissue repair, but for the appropriate concentration Ca in a solution as a buffer. McKay is not using the calcium chloride for the tissue scaffold, but for an aqueous solution containing growth factors for use in tissue repair. It would be reasonable for one of ordinary skill in the art to look at concentrations used in similar aqueous solutions for in vivo use.
In any event, Hoemann do disclose that calcium also has other purposes in their composition as an additive and therefore there are additional reasons to optimize the calcium concentration in their composition.
Applicant argues that with regard to the ratio of calcium to collagen that is recited in claim 2 that the Office’s rationale that such a ratio would be obtainable through routine optimization and experimentation using the values provided by McKay is insufficient for establishing a prima facie case of obviousness. Applicant points to In re Stepan Co as evidence that routine optimization falls short of the obviousness standard.
This is not found persuasive. With regard to the concentrations of additives in the claimed and reference compositions, generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (MPEP 2144.05).
Applicant requests that the obvious-type double patenting rejection be held in abeyance until the claims are otherwise in condition for allowance.
This is not found persuasive. The double patenting rejection should continue to be made by the examiner in each application as long as there are conflicting claims in more than one application unless that double patenting rejection is the only rejection remaining in one of the applications. See MPEP 822.01
In view of the foregoing, when all of the evidence is considered, the totality of the rebuttal evidence of nonobviousness fails to outweigh the evidence of obviousness.
Conclusion
No claims are allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Chen et al., “Injectable calcium sulfate/mineralized collagen-based bone repair materials with regulable self-setting properties”, Journal of Biomedical Materials Research Part A, 2011, Vol. 99A, No. 4, pp. 554-563.
Antonio JS, “Bone Regenerative Composition, Useful For Promoting Bone Regeneration, Hemostasis Or Wound Healing, Comprises A Suspension Of Calcium Phosphate And Collagen, And A Crosslinking Agent E.g. Transglutaminase”, US 2011/0243913 (para 91, 88).
Shoji, Daisuke, “CALCIUM PHOSPHATE CEMENT COMPOSITION AND ITS KIT FOR BONE PROSTHESIS”, US 2012/0031305, (para 40, 48, 71-73).
McKay et al., “Flowable Carrier Compositions And Methods Of Use”, US 8,048,857, (claims 1, 9 and 25).
Lynch et al., “Compositions And Methods For Arthrodetic Procedures”, US 8,106,008, (claim 50).
Gong, Yan-ming et al., “Nanometre Calcium Phosphorus Salt/collagen Composite Support Frame, Preparation Method And Application Thereof”, CN 102085392 A, published 2011-06-08, (para 9, claims 1 and 3) and machine translation.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAURA J SCHUBERG whose telephone number is (571)272-3347. The examiner can normally be reached 8:30-5:00 EST.
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LAURA J. SCHUBERG
Primary Examiner
Art Unit 1631
/LAURA SCHUBERG/ Primary Examiner, Art Unit 1631