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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on June 5, 2026 has been entered.
In that response, claim 87 was 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.
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 Lee (Lee, H.-Y., et al., Mechanical improvement of hyaluronic acid (HA) hydrogels and incorporation of polyethylene glycol (PEG) Arch. Neurol., 58 (2001), pp. 1105-1109, available at https://abstracts.biomaterials.org/data/papers/2015/abstracts/579.pdf accessed on June 24, 2026) and Altman (US 29150094269).
Collette teaches dermal fillers and methods of using such compositions to treat a condition of skin (title; abstract; paras.0002, 0012-15, 0039-43, 0117-19, 0184-96, 0320-41 (Examples 18-27); Figs. 24, 25 and accompanying text; claims 1, 7, 8, 11, 14-26). The fillers comprise a gel phase comprising (a) hydrogel particles comprising a substantially sericin-depleted silk fibroin; and (b) hydrogel particles comprising a matrix polymer including an elastic protein (claim 1). The “term ‘matrix polymer’ refers to a polymer that can become part of and/or function as an extracellular matrix polymer and pharmaceutically acceptable salts thereof”, and includes “hyaluronan, an elastic protein (like silk protein, …, silk protein-elastin-like polypeptides (SELPs),…” (para.0117; see paras.0118-19, 0126-27, 0138, 0153-54; claims 1, 3, 8, 10).
Applicant defines “silk protein fragments”: “As used herein, silk protein fragments (SPFs) refer generally to a mixture, composition, or population of peptides and/or proteins originating from silk” (para.0189, US 2023/0190997). Silk fibroin is a protein originating from silk, and SELPs comprise a population of peptides originating from silk, and therefore both are silk protein fragments (SPFs) according to this definition.
Regarding “wherein a portion of the HA and a portion of SPF are modified or crosslinked…” now in claim 87, it is noted that the claim does not require hyaluronic acid (HA) and SPF to be crosslinked together. (Applicant declined this amendment to place the application in condition for allowance. See PTO-413 (attached).) Collette teaches embodiments comprising crosslinked elastic proteins such as “a crosslinked silk protein, …a crosslinked SELP, …” (para.0138). Examples 18 and 21 at the least comprise crosslinked HA (para.0320).
“Matrix polymers disclosed herein may be crosslinked using dialdehydes and disulfides[sic] crosslinking agents including, without limitation, multifunctional PEG-based crosslinking agents, divinyl sulfones, diglycidyl ethers, and…” (para.0134 (emphases added)), i.e., polyethylene glycol diglycidyl ether (PEGDE), for “hydrogel comprising crosslinked matrix polymer”. Polyethylene has at least “about 2” ethylene glycol groups. “[E]xamples of hyaluronan crosslinking agents include divinyl sulfone (DYS), 1,4-butanediol diglycidyl ether (BDDE),…” (para.0134).
Collette teaches the silk fibroin hydrogel exhibits an elastic modulus (para.0099). Applicant states, “storage modulus G′ (also referred to as the elastic modulus)” (Specification at para. 0372, pre-grant publication US 2023/0190997). Collette teaches “three primary elastic moduli are tensile modulus, shear modulus, and bulk modulus” (para.0099). Their values are within the ranges in present claims 87 and 103-105 (paras.0101-03).
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 97 and 102, Collette teaches including lidocaine (claim 7), and the filler is injectable though fine needles of about 27 or 30 gauge (paras.0167-68).
Regarding claim 106, the dynamic or complex viscosity can be about 10 Pa.s, and adjustable (paras.0166; see paras.0161-65).
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).
Regarding claim 110, the degree of crosslinking includes about 1-15% (para.0135).
Collette does not specifically teach PEGDE for modifying or crosslinking HA, and the SPF weight-average molecular weight and polydispersity as recited in claims 87, 100, and 107.
Lee crosslinked HA using either PEGDE (MW 500) or BDDE, each at various concentrations (Methods; Figs. 1-3 and accompanying text). The crosslinker for HA in Collette was BDDE (Collette, paras.0134, 0323). “Rheological behavior” in terms of both elasticity and shear modulus (1 Hz) ranged between about 750 Pa and about 2500 Pa (Fig.3). Lee found, “compared to cross-linked HA by BDDE, PEG-cross-linked HA exhibited decreased swelling ratios and increased elasticity, indicating improved mechanical performance. Moreover, the amount of PEGDE controls swelling behavior and elasticity of the cross-linked hydrogels by means of degree of cross linking, which can optimize HA hydrogels to meet the needs of various tissue engineering applications.” (Conclusion.)
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). The molecular weight range is within that in claim 87 and the polydispersity range is identical to that in claim 100. 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, Lee, and Altman and use dermal fillers comprising silk fibroin and hyaluronic acid, each modified or crosslinked with PEGDE, wherein the SPF has 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 hydrogels for tissue engineering comprising HA, Lee teaches that for crosslinked HA, those prepared with PEGDE results in less swelling and improved elasticity as compared to those prepared with BDDE, with ability optimize PEGDE amounts depending on need.
Furthermore the selection of a known material or mechanism based on its suitability for its intended use supports a prima facie obviousness determination. MPEP §2144.07 (citations omitted). 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, see Remarks, 8 first paragraph, filed June 5, 2026, with respect to Parkes have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of Collette, Lee, and Altman.
Although new rejections are made above Applicant’s arguments are addressed now to the extent they have not been rendered moot and are relevant to the above rejections. Applicant's arguments filed June 5, 2026 have been fully considered but they are not persuasive. Applicant argues none of Collette , Parkes, and Altman teaches all of the limitations in claim 87. Specifically in Collette, “the silk fibroin is not crosslinked together with the HA”, and Parkes also does not teach crosslinking them together with PEGDE”. (Remarks, 7 first para. (emphases added), June 5, 2026.)
In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., crosslinking silk fibroin fragments and hyaluronic acid together) 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 and 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 together, and with PEGDE, as Applicant argues. As noted above Applicant declined making this clear in claim 87 by reciting, at the least, the HA and PSF being crosslinked together. See attached PTO-413.
Furthermore in response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Applicant next contends that Collette in paragraph [0099] defines elastic modulus generally, that “the elastic modulus of an object is defined as the slope of its stress-strain curve in the elastic deformation region”, whereas “[i]n contrast, storage modulus (G’) is a measure of dynamic, viscoelastic behavior…the energy stored during oscillatory deformation”, which Collette does not disclose. (Remarks, 7 third para., June 5, 2026.)
First, as noted above Applicant states in the Specification, “storage modulus G′ (also referred to as the elastic modulus)” (Specification at para. 0372, pre-grant publication US 2023/0190997). Table 17 is entitled “Rheology Terms Used to Describe Tissue Fillers”. It identifies “Elastic Modulus” as “Measure of stored energy in viscoelastic material represented by symbol G'” (Table 17 (emphasis added), para.0371). Therefore Applicant’s own disclosure contradicts the above argument.
Second, Collette discusses elastic modulus of an object as “the slope of its stress-strain curve in the elastic deformation region: A=stress/strain, where A is the elastic modulus in Pascals[sic]; stress is the force causing the deformation divided by the area to which the force is applied; and strain is the ratio of the change caused by the stress to the original state of the object. Specifying how stresses are to be measured, including directions, allows for many types of elastic moduli to be defined”, and “three primary elastic moduli are tensile modulus, shear modulus, and bulk modulus” (para.0099). Therefore Collette’s concept of “elastic modulus” contemplates an object’s responses to deformation/stress does not necessarily conflict with the storage modulus G’ as Applicant argues.
It is further noted that Collette appears to share at least one co-inventor in this application. Should Applicant pursue this argument, explanation is requested on the record to resolve the above inconsistency between Applicant’s argument versus the disclosure here and Collette. “Attorney argument is not evidence unless it is an admission, in which case, an examiner may use the admission in making a rejection.” MPEP §2145 (I).
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, 20, 21, 26, 33-35, 38, and 47 (04/27/2026) of copending Application No. 17/616,897 (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, 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 and polydispersity, 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 18 and 19 of U.S. Patent No. 12611484 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 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 Collette teaches lidocaine and PEGDE for crosslinking silk proteins or SELPs.
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.
Response to Arguments
Applicants requested that the provisional rejection(s) be held in abeyance. (Remarks, 8-9.)
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
No claim is allowed.
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.
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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
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