DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Claims
Acknowledgement is made of the response filed on September 30, 2025. In that response, claims 87 and 102 were amended. Claims 87, 89, 93-95, 97, 98, and 100-110 are treated on the merits in this action. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Information Disclosure Statement
The information disclosure statement filed September 30, 2025 fails to comply with 37 CFR 1.98(a)(2), which requires a legible copy of each cited foreign patent document; each non-patent literature publication or that portion which caused it to be listed; and all other information or that portion which caused it to be listed. It has been placed in the application file, but the information referred to therein has not been considered. Specifically non-patent literature numbers 7 and 8 are not in the submissions. Regarding NPL no.3, Brazilian application document and a translation is found, but the dates on both documents are different than that listed.
Claim Objections
Claim 87 is objected to because of the following informalities: “the” or “said” should precede “modification or cross-linking” in the second-last line. Appropriate correction is required.
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 87, 89, 93-95, 97, 98, and 100-110 are rejected under 35 U.S.C. 103 as being unpatentable over Collette (US 20110129531) in view of Parkes (Parkes, M., et al., Tribology-optimised silk protein hydrogels for articular cartilage repair, Tribology International 89 (2015) 9-18) and Altman (US 20150094269).
Collette teaches dermal fillers and methods of using such compositions to treat a condition of skin, which fillers comprise hyaluronic acid, silk fibroin, and lidocaine (title; abstract; paras.0002, 0012-15, 0039-43, 0117-18, paras. 0320-41 (Examples 18-27); Figs. 24, 25 and accompanying text; claims 1, 7, 8, 14-26). The filler is injectable though fine needles of about 27 or 30 gauge (paras.0167-68). Collette teaches “multifunctional PEG-based crosslinking agents …diglycidyl ethers” for “hydrogel comprising crosslinked matrix polymer”, and 1,2-bis(2,3-epoxypropoxy)ethylene (EGDGE) or ethylene glycol diglycidyl ether for crosslinking hyaluronan (paras.0134-35 (emphases added)).
The silk fibroin hydrogel exhibits an elastic modulus (para.0099) which Applicant discloses is also known as storage modulus (G’) (Specification at para. 0372, pre-grant publication US 2021/0190997). Collette teaches “three primary elastic moduli are tensile modulus, shear modulus, and bulk modulus” (para.0099) with values within the ranges in present claims 87 and 103-105 (paras.0101-03). The dynamic or complex viscosity can be about 10 Pa.s, and adjustable (paras.0166; see paras.0161-65).
Regarding claims 94, 95, and 97 which recite the properties of the tissue filler or its effect upon administration, a clause that “simply expresses the intended result of a process step positively recited” in a method claim is not given weight. MPEP §2111.04(I)(citations omitted). The features in these claims would occur as a result of the administering step in claim 87. Thus the clause raises a question as to the limiting effect of the claim language. Such a clause “in a method claim is not given weight when it simply expresses the intended result of a process step positively recited”, as in the instant claim. MPEP § 2111.04 (I) (citations omitted).
Regarding claims 108 and 109, Collette teaches various filler formulations comprising silk fibroin concentrations ranging from 0 mg/g to 33.75 mg/g and HA concentrations ranging from 6 mg/g to 24.0 mg/g among others (Example 20, paras.0323-24, Table 11; Example 21, paras.0326-27, Table 12; claim 9). For result-effective variables, in the case where claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. MPEP § 2144.05 (citations omitted). Furthermore, optimization within prior art conditions or through routine experimentation does not support patentability absent comparative evidence of criticality of the claimed range. See MPEP § 2144.05 (II) (citations omitted).
The degree of crosslinking includes about 1-15% (para.0135).
Collette does not specifically teach polyethylene glycol diglycidyl ether (PEGDE), the SPF weight-average molecular weight, or polydispersity recited in claims 87, 100, and 107.
Parkes teaches hydrogels made from crosslinking silk fibroin with PEGDE, MWn 532 which would have about 9 PEG units (p.10-11 section 2.2; see abstract). Varying the concentrations of silk and crosslinker resulted in hydrogels having a range of mechanical properties (Table 2 and accompanying text).
Altman is drawn to “silk fibroin-based protein fragments that are substantially devoid of sericin, wherein the composition has an average weight average molecular weight ranging from about 17 kDa to about 38 kDa, wherein the composition has a polydispersity of between about 1.5 and about 3.0” (abstract). Altman teaches biocompatible compositions comprising its silk fibroin-based protein fragments and hyaluronic acid (paras.0004, 0007-11, 0019, 0122, 0130; claim 30).
It would have been prima facie obvious for one having ordinary skill in the art before the effective filing date to combine the teachings of Collette, Parkes, and Altman and use dermal fillers comprising silk fibroin and hyaluronic acid crosslinked with PEGDE, and having the molecular weights and polydispersity as recited in the instant claims. The skilled person would have been motivated to do so because all are drawn to injectable dermal fillers comprising hyaluronic acid, Collette teaches PEG-based and other crosslinking agents, e.g., 1,2-bis(2,3-epoxypropoxy)ethylene (EGDGE) or ethylene glycol diglycidyl ether, for embodiments including hyaluronan (paras.0134-35), and Parkes teaches successfully using PEGDE to prepare silk fibroin hydrogels and in various relative concentrations. Substituting equivalents known for the same purpose, where the equivalency has been recognized in the prior art, presents strong evidence of obviousness; an express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. MPEP §2144.06 (II) (citations omitted).
Furthermore the skilled person would have been motivated to use Altman’s silk protein fragments because Altman teaches that its silk protein fragments are “biocompatible, non-sensitizing, and non-immunogenic” (para.0006), and suitable for forming gels that “ can replenish moisture and increase cell renewal while restoring radiance” of skin (para.0004).
Response to Arguments
Applicant's arguments filed September 30, 2025 have been fully considered but they are not persuasive. Applicant argues that the skilled person would not have combined teachings of Collette and Parkes because Collette is drawn to dermal fillers formulation for injection through a 27 gauge needle whereas Parkes is drawn to silk articular scaffolds and their combination “would frustrate the injectability requirement of Collette’s dermal filler”. (Remarks, 6, September 30, 2025.)
In response it is noted that 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). Here Collette teaches dermal fillers comprising hyaluronan and silk fibroin, “multifunctional PEG-based crosslinking agents …diglycidyl ethers” for “hydrogel comprising crosslinked matrix polymer” (para.0134 (emphases added)). Parkes teaches successfully using PEGDE to prepare silk fibroin hydrogels and in various relative concentrations. Substituting equivalents known for the same purpose, i.e., crosslinking agents, where the equivalency has been recognized in the prior art, presents strong evidence of obviousness; an express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. MPEP §2144.06 (II) (citations omitted).
Applicant also argues, “Parkes is focused on crosslinking silk alone, and provides no insight into crosslinking a mixture of silk and HA”. (Remarks, 7, September 30, 2025.)
However it is noted that the features upon which applicant relies (i.e., "crosslinking a mixture of silk and HA") are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). Claim 87 recites “wherein a portion of HA or SPF is modified or crosslinked…” in the second “wherein” clause, “crosslinked HA or SPF” in the next “wherein” clause, and “modification or crosslinking is…” in the last “wherein” clause. Therefore it does not require crosslinking a mixture of silk and HA as Applicant argues.
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 87, 89, 93-95, 97, 98, and 100-110 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 21, 26, 33, 34, 38, and 47 (03/28/2025) of copending Application No. 17/616,897 (reference application) in view of Collette (US 20110129531) and Parkes (Parkes, M., et al., Tribology-optimised silk protein hydrogels for articular cartilage repair, Tribology International 89 (2015) 9-18).
Although the claims at issue are not identical, they are not patentably distinct from each other because both claim sets are drawn to a method of treating a condition in a subject in need thereof, including skin conditions (claims 89, 1, 47), comprising administering to the subject a therapeutically effective amount of an injectable (claims 87, 38) tissue filler comprising silk fibroin fragments having overlapping ranges of a weight average molecular weight, hyaluronic acid (HA; claims 87, 26), and polyethylene glycol diglycidyl ether (PEGDE) cross linkage, wherein PEGDE comprises two or more ethylene glycol groups (claims 33, 34). The ‘897’s claims recite a narrower ranges of SPF weight average molecular weight and hyaluronic acid concentration. The present claims further recite an anesthetic agent and a storage modulus from about 25 Pa to about 1500 Pa. However Collette teaches dermal fillers comprising hyaluronic acid, silk fibroin, and lidocaine (title; abstract; paras.0002, 0012-15, 0039-43, 0117-18, paras. 0320-41 (Examples 18-27); Figs. 24, 25 and accompanying text; claims 1, 7, 8, 14-26). The silk fibroin hydrogel exhibits an elastic modulus (para.0099) which Applicant discloses is also known as storage modulus (G’) (Specification at para. 0372, pre-grant publication US 2021/0190997). Collette further teaches “three primary elastic moduli are tensile modulus, shear modulus, and bulk modulus” (para.0099) with values within the ranges in present claims 87 (paras.0101-03) for the ability of the hydrogel to resist deformation and to be non-permanently deformed when a force is applied to it (para.0099).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 87, 89, 93-95, 97, 98, and 100-110 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 114 and 115 of copending Application No. 18/306,965 (reference application) in view of Parkes (Parkes, M., et al., Tribology-optimised silk protein hydrogels for articular cartilage repair, Tribology International 89 (2015) 9-18) and Collette (US 20110129531).
Although the claims at issue are not identical, they are not patentably distinct from each other because both claim sets are drawn to a method of treating a condition in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a tissue filler comprising hyaluronic acid (HA), and silk fibroin protein fragments (SPF) having an identical range of average weight average molecular weight (about 1 kDa to about 250 kDa) and a polydispersity of between 1 and about 5.0, wherein a portion of the HA or SPF is modified or crosslinked by one or more linker moieties comprising one or more of an alkane or alkyl] chain, an ether group, and a secondary alcohol, and wherein the tissue filler has a storage modulus (G’) of from about 25 Pa to about 1500 Pa. The differences are that the present claims further recite an anesthetic agent and poly(ethylene glycol) diglycidyl ether; however Parkes teaches the same with about 9 ethylene glycol groups, and it would have been prima facie obvious for the skilled person to substitute an equivalent crosslinker known to crosslink silk fibroin. Furthermore Collette teaches injectable dermal fillers comprising hyaluronic acid, silk fibroin, and lidocaine (title; abstract; paras.0002, 0012-15, 0039-43, 0117-18, paras. 0320-41 (Examples 18-27); Figs. 24, 25 and accompanying text; claims 1, 7, 8, 14-26) and the skilled person would have been motivated to include lidocaine to reduce discomfort of the patient during injection.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 87, 89, 93-95, 97, 98, and 100-110 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 37 and 38 of copending Application No. 18/982,351 (reference application) in view of Collette (US 20110129531).
Although the claims at issue are not identical, they are not patentably distinct from each other because both claim sets are drawn to a method of treating a condition in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a tissue filler comprising silk fibroin or silk fibroin fragments, hyaluronic acid (HA), and polyethylene glycol (PEG), and poly(ethylene glycol) diglycidyl ether crosslinker (claim 12) which comprises 2 or more ethylene glycol groups. The differences are that the present claims further recite an anesthetic agent and a storage modulus from about 25 Pa to about 1500 Pa. Collette teaches dermal fillers comprising hyaluronic acid, silk fibroin, and lidocaine (title; abstract; paras.0002, 0012-15, 0039-43, 0117-18, paras. 0320-41 (Examples 18-27); Figs. 24, 25 and accompanying text; claims 1, 7, 8, 14-26) and the skilled person would have been motivated to include lidocaine to reduce discomfort of the patient during injection. Collette further teaches “three primary elastic moduli are tensile modulus, shear modulus, and bulk modulus” (para.0099) with values within the ranges in present claims 87 (paras.0101-03) for the ability of the hydrogel to resist deformation and to be non-permanently deformed when a force is applied to it (para.0099).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 87, 89, 93-95, 97, 98, and 100-110 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 44 and 53-55 of copending Application No. 18/002,337 (reference application) in view of Parkes (Parkes, M., et al., Tribology-optimised silk protein hydrogels for articular cartilage repair, Tribology International 89 (2015) 9-18) and Collette (US 20110129531).
Although the claims at issue are not identical, they are not patentably distinct from each other because both claim sets are drawn to a method of treating a condition in a subject in need thereof, comprising injecting to the subject a therapeutically effective amount of a biocompatible composition comprising silk fibroin or silk fibroin fragments, hyaluronic acid (HA), and polyethylene glycol (PEG) and/or polypropylene glycol (PPG), wherein a portion of the HA is modified or crosslinked by one or more linker moieties comprising one or more of polyethylene glycol (PEG), polypropylene glycol (PPG), and a secondary alcohol, wherein a portion of the silk fibroin or silk fibroin fragments are free and/or uncrosslinked, wherein a portion of the silk fibroin or silk fibroin fragments are modified or crosslinked, wherein the silk fibroin or silk fibroin fragments have a polydispersity of between 1 and about 5.0, and wherein modification or cross-linking is obtained using as cross-linker a diglycidyl-PEG. The differences are that the present claims further recite an anesthetic agent and poly(ethylene glycol) diglycidyl ether (PEGDE) and wherein the linger comprises a PEG comprising about 2-25 ethylene glycol groups. However Parkes teaches the same with about 9 ethylene glycol groups, and it would have been prima facie obvious for the skilled person to substitute an equivalent crosslinker known to crosslink silk fibroin. Furthermore Collette teaches injectable dermal fillers comprising hyaluronic acid, silk fibroin, and lidocaine (title; abstract; paras.0002, 0012-15, 0039-43, 0117-18, paras. 0320-41 (Examples 18-27); Figs. 24, 25 and accompanying text; claims 1, 7, 8, 14-26) and the skilled person would have been motivated to include lidocaine to reduce discomfort of the patient during injection.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Applicants requested that the provisional rejection(s) be held in abeyance. (Remarks, 7.)
The provisional double patenting rejection(s) is/are maintained for the reasons discussed herein. They will be maintained until Applicant submits properly executed terminal disclaimer or arguments that effectively overcome the rejection(s).
CONCLUSION
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to H. S. PARK whose telephone number is (571)270-5258. The examiner can normally be reached on weekdays.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Ali Soroush can be reached at (571)272-9925. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/H. SARAH PARK/Primary Examiner, Art Unit 1614