DETAILED ACTION
Receipt is acknowledged of applicant’s Amendment/Remarks filed 11/20/2025.
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, 9-11, 14 and 21 have been amended. Claims 3, 5 and 8 are cancelled. No claims are newly added. Accordingly, claims 1, 2, 4, 6, 7 and 9-21 remain pending in the application. Claims 17-20 stand withdrawn from further consideration, without traverse. Claims 1, 2, 4, 6, 7, 9-16 and 21 are currently under examination.
Withdrawn Rejections
Applicant’s amendment renders the rejection under 35 USC 112(b) for the term “slowly resorbable” moot. Specifically, the claims have been amended to include particular slowly resorbable materials. Thus, said rejection has been withdrawn.
Applicant’s amendment renders the rejections of claims 11 and 14 under 35 USC 112(d) moot. Specifically, the claims have been amended to remedy the further limiting issues. Thus, said rejections have been withdrawn.
Response to Declaration under 37 CFR 1.132
The Declaration under 37 CFR 1.132 filed 2/24/2025 is insufficient to overcome the rejection of claims 1, 2, 4, 6-16 and 21 under 35 USC 103 over Devore in view of Cohen as set forth in the last Office action.
The Declaration compares a collagen gel of Devore (sample 1) with mixtures of the collagen gel with 10% (sample 2), 20% (sample 3) and 30% (sample 3) hydroxyapatite (HAP) microspheres, respectively. Table 1 demonstrates the rheology properties between each of the samples. The SEM images provided in paragraph 7 of the Declaration show structural layered changes between the collagen gel sample and the collagen/HAP microsphere samples. Paragraph 8 further provides an image comparing the samples.
MPEP 716.02(d) states,
Whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the "objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support." In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range. In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980) (Claims were directed to a process for removing corrosion at "elevated temperatures" using a certain ion exchange resin (with the exception of claim 8 which recited a temperature in excess of 100°C). Appellant demonstrated unexpected results via comparative tests with the prior art ion exchange resin at 110°C and 130°C. The court affirmed the rejection of claims 1-7 and 9-10 because the term "elevated temperatures" encompassed temperatures as low as 60°C where the prior art ion exchange resin was known to perform well. The rejection of claim 8, directed to a temperature in excess of 100°C, was reversed.). See also In re Peterson, 315 F.3d 1325, 1329-31, 65 USPQ2d 1379, 1382-85 (Fed. Cir. 2003) (data showing improved alloy strength with the addition of 2% rhenium did not evidence unexpected results for the entire claimed range of about 1-3% rhenium); In re Grasselli, 713 F.2d 731, 741, 218 USPQ 769, 777 (Fed. Cir. 1983) (Claims were directed to certain catalysts containing an alkali metal. Evidence presented to rebut an obviousness rejection compared catalysts containing sodium with the prior art. The court held this evidence insufficient to rebut the prima facie case because experiments limited to sodium were not commensurate in scope with the claims.).
The claims recite, “wherein the non-resorbable or slowly resorbable spheres are one or more of the group consisting of: calcium hydroxyapatite microspheres; polymer coated hydroxyapatite microspheres including one or more of PEG-hydroxyapatite microspheres, poly-L-lactide-hydroxyapatite microspheres; poly-ɛ-caprolactone-hydroxyapatite microspheres; and poly(p-dioxanone)-hydroxyapatite microspheres; polymethylmethacrylate (PMMA) microspheres; polylactide and/or polyglycolide polymer and/or copolymer (PLGA) microspheres; poly-L-lactide (PLA) microspheres; polyethylene glycol (PEG) microspheres; crosslinked hyaluronic acid microspheres produced by one or more of emulsified crosslinking reaction, double emulsion evaporation method, microfluidic crosslinking reaction, and stamp formation; and L-lactide/trimethylene carbonate copolymer granules”.
The evidence provided only compares a single species of microspheres, calcium hydroxyapatite microspheres. Thus, the evidence provided is not commensurate in scope with the claimed invention.
Further, the image provided in paragraph 8 of the Declaration is unclear. Applicant asserts that the collagen/HAP microsphere samples led to a better tissue augmentation effect than the collagen only sample, however it is not apparent from the image that is the case. Applicants have the burden of explained the data in any declaration the proffer as evidence of non-obviousness (MPEP 716.02(b)).
For these reasons, the Declaration is ineffective in overcoming the rejection of claims 1, 2, 4, 6-16 and 21 under 35 USC 103 over Devore in view of Cohen.
Maintained Rejections
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.
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, 2, 4, 6, 7, 9-16 and 21 stand rejected under 35 U.S.C. 103 as being unpatentable over Devore et al. (USPN 10,111,981 B2, Oct. 30, 2018, hereafter as “Devore”) in view of Cohen et al. (“Artecoll: A Long-Lasting Injectable Wrinkle Filler Material: Report of a Controlled, Randomized, Multicenter Clinical Trial of 251 Subjects”, Plastic and Reconstructive Surgery 114(4):p 964-976, September 15, 2004; hereafter as “Cohen”).
The claimed invention is drawn to a composition for application in soft tissue augmentation comprising (i) one or more of a derivatized collagen solution, rapidly polymerizing collagen gel (before undergoing fibrillogenesis), or crosslinked collagen fibrils; and (ii) about 10 to about 30% non-resorbable or slowly resorbable spheres by weight of part (i), the non-resorbable or slowly resorbable spheres having a diameter of about 20 to about 50 µm, wherein the amount of collagen in part (i) is from over 5 wt% to 10 wt% based on the total weight of the composition, wherein, if present, the derivatized collagen is collagen derivatized with acetylation agents that alter the pKa of the collagen and has one or more of the following features: (a) soluble at neutral pH; (b) does not undergo fibrillogenesis at physiological pH; and/or (c) precipitates at acidic pH, and wherein, if present, the rapidly polymerizing collagen gel comprises a neutralized solution comprising an acid soluble collagen, EDTA, and a polyol, and wherein the acid soluble collagen comprises one or more of Type I collagen, Type III collagen, and combinations thereof, and wherein the non-resorbable or slowly resorbable spheres are one or more of the group consisting of: calcium hydroxyapatite microspheres; polymer coated hydroxyapatite microspheres including one or more of PEG- hydroxyapatite microspheres, poly-L-lactide-hydroxyapatite microspheres; poly-ɛ-caprolactone-hydroxyapatite microspheres; and poly(p-dioxanone)-hydroxyapatite microspheres; polymethylmethacrylate (PMMA) microspheres; polylactide and/or polyglycolide polymer and/or copolymer (PLGA) microspheres; poly-L-lactide (PLA) microspheres; polyethylene glycol (PEG) microspheres; crosslinked hyaluronic acid microspheres produced by one or more of emulsified crosslinking reaction, double emulsion evaporation method, microfluidic crosslinking reaction, and stamp formation; and L-lactide/trimethylene carbonate copolymer granules.
Regarding instant claim 1, Devore teaches injectable acid soluble collagen compositions comprising a neutralized solution of an acid soluble collagen, EDTA and preferably a polyol, wherein the composition is injectable at physiological pH and the acid soluble collagen polymerizes upon exposure to tissue and forms a gel (i.e., rapidly polymerizing collagen gel) (Abstract). Said composition is suitable for soft tissue augmentation (Abstract; paragraph bridging cols 2-3). Devore exemplifies a rapidly polymerizing collagen gel comprising a neutralized solution comprising an acid soluble collagen, EDTA, and a polyol, wherein the soluble collagen comprises collagen selected from the group consisting of Type 1 collagen, Type III collagen and combinations thereof (Abstract; Example 5; claim 1). Devore teaches that the collagen is present in a concentration between 5-70 mg/ml (0.5-7.0%) (col. 4, lines 14-18).
Devore is silent to about to 10 to about 30% non-resorbable or slowly resorbable spheres by weight of part (i) having a diameter of about 20 to 50 µm as well as the particular microsphere materials claimed (e.g., PMMA microspheres).
Cohen teaches an injectable wrinkle filler composed of 20 volume% polymethylmethacrylate (PMMA) microspheres having a diameter of 32-40 µm and 80 volume% bovine collagen (page 964). Cohen teaches that because the microspheres are nonbiodegradable and of a size that do not permit the microspheres to migrate or be phagocytosed by macrophages, the tissue augmentation is expected to be permanent (page 964, right col, 2nd full para.). Cohen further teaches that said PMMA microspheres are biocompatible and are combined with a collagen carrier to be able to be delivered into the deeper skin layers which eventually are encapsulated by autologous connective tissue (page 970). It is noted that the PMMA microspheres by weight of the collagen component in Cohen calculates to 25% (20% PMMA / 80% collagen).
The references are both drawn to injectable collagen-based compositions for soft tissue augmentation, thus, it would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to include PMMA microspheres having a diameter of 32-40 µm into the invention of Devore in an amount of 25% by weight of the collagen component as suggested by Cohen with a reasonable expectation of success. A skilled artisan would have been motivated to do so because Cohen teaches that the PMMA microspheres having a diameter of 32-40 µm in the amount of 25% by weight of the collagen component are suitable for the use in injectable collagen-based compositions for the purpose of soft tissue augmentation and further because said microspheres are capable of being encapsulated by autologous connective tissue and, in turn, allow for permanent tissue augmentation.
Regarding the limitation, “wherein the amount of collagen in part (i) is from over 5 wt% to 10 wt% based on the total weight of the composition”, Devore, as discussed above, teaches that the collagen is present in a concentration between 5-70 mg/ml (0.5-7.0%) (col. 4, lines 14-18) and Cohen, as discussed above, teaches that the collagen component of the microsphere/collagen composition is present in an amount of 80%. In light of the combined teachings of Devore and Cohen, it would have been prima facie obvious to one of ordinary skill in the art to combine the collagen gel of Devore in an amount of 80% and the PMMA spheres of Cohen in an amount of 20% with a reoanble expectation of success. In order to calculate the amount of collagen in the gel in the suggested collagen gel/PMMA composition, one would calculate the amount of collagen by multiplying the collagen range taught in Devore (0.5-7.0%) by the 80% collagen component taught in Cohen to arrive at a range of 0.4-5.6%. MPEP 2144.05(I) states, “In the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists”. Because the claimed range of over 5% to 10% overlaps with the suggested range of 0.4-5.6% by the prior art, a prima facie case of obviousness exists.
Regarding instant claim 2, Devore teaches that the collagen can be extracted from animal hides such as bovine or porcine hides, or may be cell derived human collagen or recombinant human collagen (col. 3, lines 47-50).
Regarding instant claim 4, said claim recites, “wherein the derivatized collagen is…” Claim 4 depends from claim 1. Claim 1 recites derivatized collagen as one option but is not a required element. Thus, claim 4 does not further require any additional elements and, as such, the teachings of Devore/Cohen read on the claim as it is currently written.
Regarding instant claim 6, Devore teaches that the acid soluble collagen is in a concentration of between 5 and 70 mg/ml, the EDTA is disodium EDTA, the EDTA is in a concentration of between 10 and 50 mM, the polyol is D-mannitol, the polyol is in a concentration of between 2.5 to 4%, the composition can further comprise fructose, sucrose or combinations thereof, and the osmolarity of the composition is 280-360 mmol/kg (claims 2-15).
Regarding instant claim 7, said claim recites, “wherein the crosslinked collagen is…” Claim 7 depends from claim 1. Claim 1 recites crosslinked collagen as one option but is not a required element and claim 7 does not recite that crosslinked collagen is required. Thus, claim 7 does not further require any additional elements and, as such, the teachings of Devore/Cohen read on the claim as it is currently written.
Regarding instant claim 9, said claim recites, “wherein the crosslinker of hyaluronic acid microspheres is…” Claim 9 depends from claim 8. Claim 8 recites crosslinked hyaluronic acid microspheres as one option but is not a required element and claim 9 does not recite that crosslinked hyaluronic acid microspheres are required. Thus, claim 9 does not further require any additional elements and, as such, the teachings of Devore/Cohen read on the claim as it is currently written.
Regarding instant claim 10, said claim recites, “wherein the crosslinked hyaluronic acid microspheres is…” Claim 10 depends from claim 8. Claim 8 recites crosslinked hyaluronic acid microspheres as one option but is not a required element and claim 10 does not recite that crosslinked hyaluronic acid microspheres are required. Thus, claim 10 does not further require any additional elements and, as such, the teachings of Devore/Cohen read on the claim as it is currently written.
Regarding instant claim 11, Devore and Cohen teach the elements discussed above. It is noted that said claim is deemed a product-by-process claim due to the limitation, “obtained through spray- precipitation technique, emulsion, double emulsion evaporation method, microfluidic reaction, solid-gel process, melt extrusion technique, sintering process or stamp formation” and “sterilized through heat moist sterilization, gamma irradiation or ethylene oxide sterilization” and as such, determination of patentability is based on the product itself, not by the method in which it is made. The claim does not further limit the product itself, therefore the teachings of Devore/Cohen meet the limitations of said claim.
Regarding instant claim 12, Devore teaches collagen in concentrations 0.5-7% of the injectable acid soluble collagen composition (col. 4, lines 15-18).
Devore is silent to the concentration of spheres being 1-55% based on the weight of the total composition.
Cohen also teaches that the PMMA microspheres are included in a concentration of 20% of the collagen/PMMA composition (page 964, right col., 2nd full para.).
The references are both drawn to injectable collagen-based compositions for soft tissue augmentation, thus, it would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to include PMMA microspheres in an amount of 20% into the invention of Devore as suggested by Cohen with a reasonable expectation of success. A skilled artisan would have been motivated to do so because Cohen teaches that the PMMA microspheres in an amount of 20% is suitable for the purpose of an injectable collagen-based composition and that is effective for permanent tissue augmentation.
Regarding instant claims 13 and 14, it is noted that claim 13 recites a range of 0-5% which implies the additive(s) are considered optional. Further, claim 14 depends from claim 13 and claim 14 does not clarify that the additive(s) are a required element. Accordingly, the additives of claim 14 are also considered optional.
Regarding instant claim 15, said claim recites, “wherein part (ii) is added to part (i) by utilizing vacuum planetary mixer to form an injectable homogenous gel…”. Said limitation is a product by process limitation due to the limitations, “added to” and “utilizing a planetary mixer”. Determination of patentability is based on the product itself, not by the method in which it is made. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process (MPEP 2113). However, the limitation, “an injectable homogenous gel” further describes the product. As discussed above, both references teach an injectable composition. Cohen specifies that the injectable composition is a homogenous composition comprising collagen and PMMA microspheres (page 964, right col., 1st full para.) and Devore describes the acid soluble collagen composition as viscous and undergoes gelation (col. 2, lines 37-47). Thus, the combination of Devore’s acid soluble collagen composition and Cohen’s PMMA microspheres would necessarily result in an injectable homogenous gel.
Regarding instant claim 16, said claim recites, “wherein part (ii) is added to a salt or pH precipitate of part (i) and resolubilized by dialysis or ultradialysis or ultrafiltration process to form a homogenous injectable gel. Said limitation is a product by process limitation due to the limitations, “added to” and “resolubilized by dialysis or ultradialysis or ultrafiltration process”. Determination of patentability is based on the product itself, not by the method in which it is made. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process (MPEP 2113). However, the limitation, “an injectable homogenous gel” further describes the product. As discussed above, both references teach an injectable composition. Cohen specifies that the injectable composition is a homogenous composition comprising collagen and PMMA microspheres (page 964, right col., 1st full para.) and Devore describes the acid soluble collagen composition as viscous and undergoes gelation (col. 2, lines 37-47). It is also further noted that Devore teaches the inclusion of salts, pH precipitates, and dialysis (Examples). Thus, the combination of Devore’s acid soluble collagen composition and Cohen’s PMMA microspheres would necessarily result in a homogenous injectable gel.
Regarding instant claim 21, said claim is drawn to a composition for application in soft tissue augmentation comprising (i) one or more of a derivatized collagen solution and rapidly polymerizing collagen gel (before undergoing fibrillogenesis); and (ii) about 10 to about 30% non-resorbable or slowly resorbable spheres by weight of part (i), the non-resorbable or slowly resorbable spheres having a diameter of about 20 to about 50 m, wherein the amount of collagen in part (i) is from over 5 wt% to 10 wt% based on the total weight of the composition, wherein, if present, the derivatized collagen is collagen derivatized with acetylation agents that alter the pKa of the collagen and has one or more of the following features: (a) soluble at neutral pH;(b) does not undergo fibrillogenesis at physiological pH; and/or (c) precipitates at acidic pH, and wherein, if present, the rapidly polymerizing collagen gel comprises a neutralized solution comprising an acid soluble collagen, EDTA, and a polyol, and wherein the acid soluble collagen comprises one or more of Type I collagen, Type III collagen, and combinations thereof. It is noted that the claim is being interpreted to require one of a) a derivatized collagen solution, b) a rapidly polymerizing collagen gel (before undergoing fibrillogenesis), or c) both a) and b). The teachings of Devore and Cohen related to claim 1, discussed above, are also relevant to claim 21 as claim 21 does not require any additional limitations. For the same reasons as discussed above (see claim 1 discussion), the combined teachings of Devore and Cohen render the claim obvious.
Thus, the combined teachings of Devore and Cohen render the instant claims prima facie obvious.
Response to Arguments
Applicant's arguments, filed 11/20/2025, regarding the 103 rejection over Devore and Cohen have been fully considered but they are not persuasive.
Applicant asserts that the claimed combination of collagen and microspheres provides unexpected results that could not have been anticipated based on the cited references. Applicant asserts that the microstructure of the collagen is sheet-like and fiber-like whereas the combination of collagen and microspheres is a very different layer-by-layer arrangement as seen in the Second Zhu Declaration. Said Declaration also demonstrates improved mechanical properties and resulting tissue augmentation efficacy. Remarks, pages 8-9.
In response, it is respectfully submitted that the evidence provided in the Second Declaration is discussed above. Said Declaration compares a collagen gel of Devore (sample 1) with mixtures of the collagen gel with 10% (sample 2), 20% (sample 3) and 30% (sample 3) hydroxyapatite (HAP) microspheres, respectively. MPEP 716.02(d) states,
Whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the "objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support." In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range. In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980) (Claims were directed to a process for removing corrosion at "elevated temperatures" using a certain ion exchange resin (with the exception of claim 8 which recited a temperature in excess of 100°C). Appellant demonstrated unexpected results via comparative tests with the prior art ion exchange resin at 110°C and 130°C. The court affirmed the rejection of claims 1-7 and 9-10 because the term "elevated temperatures" encompassed temperatures as low as 60°C where the prior art ion exchange resin was known to perform well. The rejection of claim 8, directed to a temperature in excess of 100°C, was reversed.). See also In re Peterson, 315 F.3d 1325, 1329-31, 65 USPQ2d 1379, 1382-85 (Fed. Cir. 2003) (data showing improved alloy strength with the addition of 2% rhenium did not evidence unexpected results for the entire claimed range of about 1-3% rhenium); In re Grasselli, 713 F.2d 731, 741, 218 USPQ 769, 777 (Fed. Cir. 1983) (Claims were directed to certain catalysts containing an alkali metal. Evidence presented to rebut an obviousness rejection compared catalysts containing sodium with the prior art. The court held this evidence insufficient to rebut the prima facie case because experiments limited to sodium were not commensurate in scope with the claims.). Emphasis added.
The claims recite, “wherein the non-resorbable or slowly resorbable spheres are one or more of the group consisting of: calcium hydroxyapatite microspheres; polymer coated hydroxyapatite microspheres including one or more of PEG-hydroxyapatite microspheres, poly-L-lactide-hydroxyapatite microspheres; poly-ɛ-caprolactone-hydroxyapatite microspheres; and poly(p-dioxanone)-hydroxyapatite microspheres; polymethylmethacrylate (PMMA) microspheres; polylactide and/or polyglycolide polymer and/or copolymer (PLGA) microspheres; poly-L-lactide (PLA) microspheres; polyethylene glycol (PEG) microspheres; crosslinked hyaluronic acid microspheres produced by one or more of emulsified crosslinking reaction, double emulsion evaporation method, microfluidic crosslinking reaction, and stamp formation; and L-lactide/trimethylene carbonate copolymer granules”. The evidence provided only compares a single species of microspheres, calcium hydroxyapatite microspheres, whereas the claims encompass many other types of microspheres. Thus, the evidence provided is not commensurate in scope with the claimed invention. Further, the image provided in paragraph 8 of the Declaration is unclear. Applicant asserts that the collagen/HAP microsphere samples led to a better tissue augmentation effect than the collagen only sample, however it is not apparent from the image that is the case. Applicants have the burden of explained the data in any declaration the proffer as evidence of non-obviousness (MPEP 716.02(b)). For these reasons, the evidence provided in the Second Declaration is ineffective in overcoming the rejection.
Applicant further asserts that the experimental data in the present application further verifies that, as compared to Bellafill (an upgraded product of Artecoll available from the same manufacturer), the claimed composition has remarkably and unexpectedly improved properties including longer durability, shortened or overcome the yielding period of augmentation effect. Applicant points to Example 10, Table 1 and the First Declaration to support their position. Remarks, pages 9-10.
In response, it is respectfully submitted that the evidence provided in Example 10 of the application and discussed in the First Declaration is based on a particular formulation (i.e., 20% rapidly polymerizing collagen and PMMA microspheres with diameters of 32-50 microns) that is much narrower in scope than that of the claimed invention. Similarly as discussed above, the evidence provided is not commensurate in scope with the claimed invention.
Thus, for these reasons, Applicant’s arguments are found unpersuasive. Said rejection is maintained.
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, 2, 4, 6, 7, 9-16 and 21 stand rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-26 of U.S. Patent No. 10,111,981 B2 in view of Cohen et al. (“Artecoll: A Long-Lasting Injectable Wrinkle Filler Material: Report of a Controlled, Randomized, Multicenter Clinical Trial of 251 Subjects”, Plastic and Reconstructive Surgery 114(4):p 964-976, September 15, 2004; hereafter as “Cohen”).
The instant invention is described above.
The patented invention is drawn to an injectable acid soluble collagen composition comprising, a neutralized solution comprising the acid soluble collagen, EDTA and a polyol, and wherein the acid soluble collagen comprises collagen selected from the group consisting of Type I collagen, Type III collagen and combinations thereof, a method for augmenting soft tissue comprising injecting said composition, and an implant comprising a coating, wherein the coating comprises said composition. The patent further recites, “wherein said composition comprises said acid soluble collagen in a concentration between 5 and 70 mg/ml”, “wherein said EDTA is disodium EDTA”, “wherein said composition comprises said EDTA in a concentration between 10 and 50 mM”, “wherein said polyol is D-mannitol”, “wherein the composition comprises said polyol in a concentration between 2.5% and 4% (w/v)”, “further comprising a disaccharide, fructose, or combinations thereof”, and “wherein said composition has an osmolality of 280-360 mmol/kg”. It is noted that the patent equates the acid soluble collagen in a concentration between 5 and 70 mg/ml to 0.5-7.0% w/v (col. 4, lines 14-18). It is further noted that the patented composition rapidly undergo polymerization involving initial gelation and subsequent fibrillization when contacted by or mixed with physiological fluids or other ion-containing fluids to form fibrous collagen matrices (col. 2, lines 40-44).
The patent is silent to about to 10 to about 30% non-resorbable or slowly resorbable spheres by weight of part (i) having a diameter of about 20 to 50 µm as well as the particular microsphere materials claimed (e.g., PMMA microspheres).
Cohen teaches an injectable wrinkle filler composed of 20 volume% polymethylmethacrylate (PMMA) microspheres having a diameter of 32-40 µm and 80 volume% bovine collagen (page 964). Cohen teaches that because the microspheres are nonbiodegradable and of a size that do not permit the microspheres to migrate or be phagocytosed by macrophages, the tissue augmentation is expected to be permanent (page 964, right col, 2nd full para.). Cohen further teaches that said PMMA microspheres are biocompatible and are combined with a collagen carrier to be able to be delivered into the deeper skin layers which eventually are encapsulated by autologous connective tissue (page 970). It is noted that the PMMA microspheres by weight of the collagen component in Cohen calculates to 25% (20% PMMA / 80% collagen).
The patent and Cohen are both drawn to injectable collagen-based compositions for soft tissue augmentation, thus, it would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to include PMMA microspheres having a diameter of 32-40 µm into the patent in an amount of 25% by weight of the collagen component as suggested by Cohen with a reasonable expectation of success. A skilled artisan would have been motivated to do so because Cohen teaches that the PMMA microspheres having a diameter of 32-40 µm in the amount of 25% by weight of the collagen component are suitable for the use in injectable collagen-based compositions for the purpose of soft tissue augmentation and further because said microspheres are capable of being encapsulated by autologous connective tissue and, in turn, allow for permanent tissue augmentation.
Regarding the limitation, “wherein the amount of collagen in part (i) is from over 5 wt% to 10 wt% based on the total weight of the composition”, the patent, as discussed above, teaches that the collagen is present in a concentration between 5-70 mg/ml (0.5-7.0%) (col. 4, lines 14-18) and Cohen, as discussed above, teaches that the collagen component of the microsphere/collagen composition is present in an amount of 80%. In light of the combined teachings of the patent and Cohen, it would have been prima facie obvious to one of ordinary skill in the art to combine the collagen gel of patent in an amount of 80% and the PMMA spheres of Cohen in an amount of 20% with a reoanble expectation of success. In order to calculate the amount of collagen in the gel in the suggested collagen gel/PMMA composition, one would calculate the amount of collagen by multiplying the collagen range taught in the patent (0.5-7.0%) by the 80% collagen component taught in Cohen to arrive at a range of 0.4-5.6%. MPEP 2144.05(I) states, “In the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists”. Because the claimed range of over 5% to 10% overlaps with the suggested range of 0.4-5.6% by the prior art, a prima facie case of obviousness exists.
Thus, the instant claims are unpatentable over the patented claims in view of Cohen.
Response to Arguments
Applicant's arguments filed, 11/20/2025, regarding the double patenting rejection over USPN 10,111,981 in view of Cohen have been fully considered but they are not persuasive.
Applicant argues that the recited combination of the collagen and the non-resorbable or slowly resorbable spheres provides surprising and unexpected results that could not have been predicted based on the combination of the claims of ‘981 patent or ‘089 patent and Cohen. Remarks, page 12.
In response, it is respectfully submitted that for the same reasons as discussed above, applicant’s arguments regarding surprising and unexpected results are not found persuasive.
Thus, said rejection has been modified to account for Applicant’s amendments.
Claims 1, 2, 4, 6, 7, 9-16 and 21 stand rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 11,235,089 B2 in view of Cohen et al. (“Artecoll: A Long-Lasting Injectable Wrinkle Filler Material: Report of a Controlled, Randomized, Multicenter Clinical Trial of 251 Subjects”, Plastic and Reconstructive Surgery 114(4):p 964-976, September 15, 2004; hereafter as “Cohen”).
The instant invention is described above.
The patented invention is drawn to a method for augmenting soft tissue, comprising, injecting into a soft tissue deficiency a neutralized solution comprising EDTA and an acid soluble collagen selected from the group consisting of Type 1 collagen, Type III collagen and combinations thereof, wherein the collagen in the solution has not undergone fibrillogenesis prior to injection; wherein the EDTA concentration in the solution is from 25 mM to 40 mM, and wherein the collagen has been dialyzed against EDTA; wherein said soft tissue deficiency is selected from the group consisting of wrinkles, dermal folds, dermal laxity, skin contour defects, dermal fine lines, dermal furrows and dermal unevenness; wherein said acid soluble collagen undergoes fibrillogenesis upon exposure to the soft tissue to form an opaque collagen fibril matrix; and wherein the collagen fibril matrix augments the soft tissue deficiency. The patent further recites, “wherein said composition comprises said acid soluble collagen in a concentration between 5 and 70 mg/ml”, “wherein said polyol is D-mannitol”, “wherein the composition comprises said polyol in a concentration between 2.5% and 4% (w/v)”, and “wherein the composition further comprises a disaccharide, fructose, or combinations thereof”. It is noted that the patent equates the acid soluble collagen in a concentration between 5 and 70 mg/ml to 0.5-7.0% w/v (col. 4, lines 32-36). It is further noted that the patented composition rapidly undergo polymerization involving initial gelation and subsequent fibrillization when contacted by or mixed with physiological fluids or other ion-containing fluids to form fibrous collagen matrices (col. 2, lines 59-63).
The patent is silent to about to 10 to about 30% non-resorbable or slowly resorbable spheres by weight of part (i) having a diameter of about 20 to 50 µm as well as the particular microsphere materials claimed (e.g., PMMA microspheres).
Cohen teaches an injectable wrinkle filler composed of 20 volume% polymethylmethacrylate (PMMA) microspheres having a diameter of 32-40 µm and 80 volume% bovine collagen (page 964). Cohen teaches that because the microspheres are nonbiodegradable and of a size that do not permit the microspheres to migrate or be phagocytosed by macrophages, the tissue augmentation is expected to be permanent (page 964, right col, 2nd full para.). Cohen further teaches that said PMMA microspheres are biocompatible and are combined with a collagen carrier to be able to be delivered into the deeper skin layers which eventually are encapsulated by autologous connective tissue (page 970). It is noted that the PMMA microspheres by weight of the collagen component in Cohen calculates to 25% (20% PMMA / 80% collagen).
The patent and Cohen are both drawn to injectable collagen-based compositions for soft tissue augmentation, thus, it would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to include PMMA microspheres having a diameter of 32-40 µm into the patent in an amount of 25% by weight of the collagen component as suggested by Cohen with a reasonable expectation of success. A skilled artisan would have been motivated to do so because Cohen teaches that the PMMA microspheres having a diameter of 32-40 µm in the amount of 25% by weight of the collagen component are suitable for the use in injectable collagen-based compositions for the purpose of soft tissue augmentation and further because said microspheres are capable of being encapsulated by autologous connective tissue and, in turn, allow for permanent tissue augmentation.
Regarding the limitation, “wherein the amount of collagen in part (i) is from over 5 wt% to 10 wt% based on the total weight of the composition”, the patent, as discussed above, teaches that the collagen is present in a concentration between 5-70 mg/ml (0.5-7.0%) (col. 4, lines 14-18) and Cohen, as discussed above, teaches that the collagen component of the microsphere/collagen composition is present in an amount of 80%. In light of the combined teachings of the patent and Cohen, it would have been prima facie obvious to one of ordinary skill in the art to combine the collagen gel of patent in an amount of 80% and the PMMA spheres of Cohen in an amount of 20% with a reoanble expectation of success. In order to calculate the amount of collagen in the gel in the suggested collagen gel/PMMA composition, one would calculate the amount of collagen by multiplying the collagen range taught in the patent (0.5-7.0%) by the 80% collagen component taught in Cohen to arrive at a range of 0.4-5.6%. MPEP 2144.05(I) states, “In the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists”. Because the claimed range of over 5% to 10% overlaps with the suggested range of 0.4-5.6% by the prior art, a prima facie case of obviousness exists.
Thus, the instant claims are unpatentable over the patented claims in view of Cohen.
Response to Arguments
Applicant's arguments filed, 11/20/2025, regarding the double patenting rejection over USPN 10,111,981 in view of Cohen have been fully considered but they are not persuasive.
Applicant argues that the recited combination of the collagen and the non-resorbable or slowly resorbable spheres provides surprising and unexpected results that could not have been predicted based on the combination of the claims of ‘981 patent or ‘089 patent and Cohen. Remarks, page 12.
In response, it is respectfully submitted that for the same reasons as discussed above, applicant’s arguments regarding surprising and unexpected results are not found persuasive.
Thus, said rejection has been modified to account for Applicant’s amendments.
New Rejections
In light of Applicant’s amendments, the following rejections have been newly added:
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 2, 4, 6, 7, 9-16 and 21 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
37 CFR §1.118 (a) states that "No amendment shall introduce new matter into the disclosure of an application after the filing date of the application".
There is no explicit or implicit teaching in the disclosure as originally filed for polymer coated hydroxyapatite microspheres including one or more of PEG-hydroxyapatite microspheres, poly-L-lactide-hydroxyapatite microspheres; poly-ɛ-caprolactone-hydroxyapatite microspheres; and poly(p-dioxanone)-hydroxyapatite microspheres (instant claims 1 and 21); the subject matter was not properly described as filed. The specification discloses PEG-hydroxyapatite microspheres, poly-L-lactide-hydroxyapatite microspheres, poly-ɛ-caprolactone-hydroxyapatite microspheres, and poly(p-dioxanone)-hydroxyapatite microspheres (page 14, embodiment 8), however there is no mention of a coating. The only support located in the specification for an embodiment directed to coated microspheres is crosslinked hyaluronic acid microspheres coated with biodegradable polymers, poly-L-lactide (PLA), polyethylene glycol (PEG), or PLGA, or poly(p-dioxanone) (PDO) (page 14, embodiment 10). Applicant is invited to identify the portion of the specification that teaches said limitation, as the examiner has not been able to locate the applicable disclosure. The claims within this rejection are examined as written by the applicant; at this time new matter must be considered as part of the claimed subject matter.
MPEP 2163.06 notes: "If new matter is added to the claims, the examiner should reject the claims under 35 U.S.C. 112, first paragraph - written description requirement. In re Rasmussen, 650 F.2d 1212, 211 USPQ 323 (CCPA 1981)." MPEP 2163.02 teaches that "Whenever the issue arises, the fundamental factual inquiry is whether a claim defines an invention that is clearly conveyed to those skilled in the art at the time the application was filed...If a claim is amended to include subject matter, limitations, or terminology not present in the application as filed, involving a departure from, addition to, or deletion from the disclosure of the application as filed, the examiner should conclude that the claimed subject matter is not described in that application. MPEP 2163.06 further notes "When an amendment is filed in reply to an objection or rejection based on 35 U.S.C. 112, first paragraph, a study of the entire application is often necessary to determine whether or not "new matter" is involved. Applicant should therefore specifically point out the support for any amendments made to the disclosure".
This is a new matter rejection. Correction is respectfully requested.
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, 2, 4, 6, 7, 9-16 and 21 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.
Regarding claims 1 and 21, said claims recite, “wherein the non-resorbable or slowly resorbable spheres are one or more of the group consisting of: calcium hydroxyapatite microspheres; polymer coated hydroxyapatite microspheres including one or more of PEG- hydroxyapatite microspheres, poly-L-lactide-hydroxyapatite microspheres; poly-ɛ-caprolactone-hydroxyapatite microspheres; and poly(p-dioxanone)-hydroxyapatite microspheres...” (emphasis added). The claim sets out a Markush group of non-resorbable or slowly resorbable spheres, however within the Markush group, one of the alternatives recites, polymer coated hydroxyapatite microspheres including one or more of PEG- hydroxyapatite microspheres, poly-L-lactide-hydroxyapatite microspheres; poly-ɛ-caprolactone-hydroxyapatite microspheres; and poly(p-dioxanone)-hydroxyapatite microspheres”. The phrase "including" at line 19 in each claim renders the claims indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). Dependent claims 2, 4, 6, 7, 9-16 and 21 do not remedy the indefinite issue and as such said dependent claims suffer from the same deficiency.
Conclusion
All claims have been rejected; no claims are allowed.
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.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CASEY HAGOPIAN whose telephone number is (571)272-6097. The examiner can normally be reached on M-F 9:00 am - 5:00 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sue Liu can be reached on 571-272-5539. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Casey S. Hagopian
Examiner, Art Unit 1617
/CARLOS A AZPURU/Primary Examiner, Art Unit 1617