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 .
Election/Restrictions
Applicant’s election without traverse of claims 30-43 in the reply filed on 3/3/2026 is acknowledged.
Claims 21-29 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 3/3/2026.
Priority
This application is a CON of 17/716,743 (4/8/2022); which is a CON of 16/795,921 (2/20/2020); which is a CON of 16/453,620 (6/26/2019); which is a CON of 16/184,098 (11/8/2018); which is a CON of 14/876,792 (10/6/2015); which is a CON of 14/503,021 (9/30/2014); which claims benefit of 62/036,450 (8/12/2014); 62/000,928 (5/20/2014); and 61/884,820 (9/30/2013).
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 112(a) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosures of the prior-filed applications, Application Nos. 62/036,450; 62/000,928; and 61/884,820; fail to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. Provisional application 61/884,820 does not disclose a substantially solid silk fibroin composition wherein the silk fibroin protein fragments have an average weight average molecular weight selected from among the ranges recited in claim 30. None of provisional applications 62/036,450; 62/000,928; or 61/884,820 disclose silk fibroin fragments which do not visibly change in color or turbidity for at least 10 days as recited in claim 30.
The first disclosure of silk fibroin fragments which do not visibly change in color or turbidity for at least 10 days is in 14/503,021. Therefore, the effective filing date of claims 30-43 is 9/30/2014.
Information Disclosure Statement
The information disclosure statement(s) (IDS) filed on 11/10/2023, 5/15/2024, 10/1/2024, 1/17/2025, 2/6/2025, 6/10/2025, 12/23/2025, and 3/3/2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 30-43 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.
The term “substantially” in claim 30 is a relative term which renders the claim indefinite. The term “substantially” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
There is no disclosure of what is meant by “substantially solid”, and as such it is unclear what specific form the composition is in, or what threshold of solidity is required to be considered substantially solid. The instant specification states that the term "substantially homogeneous" may refer to pure silk fibroin-based protein fragments that are distributed in a normal distribution about an identified molecular weight; or may refer to an even distribution of additive, for example vitamin C, throughout a composition of the present disclosure (see specification p. 27). However, these are merely exemplary and a skilled artisan would not be apprised of the full scope and structure of a substantially homogeneous solution. Similarly, the instant specification sets forth various embodiments of silk fibers which are substantially devoid of sericin, however these are merely exemplary and a skilled artisan would not be apprised of the full scope of “substantially devoid of sericin”.
Further, regarding claims 30 and 43, the limitation “do not spontaneously or gradually gelate and do not visibly change in color or turbidity for at least 10/30 days” is indefinite. First, it is not clear what is meant by “gradually gelate”. The term gradually is not defined in the specification to make clear how gradual gelation would be measured or determined, i.e. how slowly gelation must occur to be considered gradual gelation. Additionally, it is not clear if it is meant that the silk fibroin fragments do not spontaneously or gradually gelate for at least 10 or 30 days; or if it is meant that the silk fibroin fragments do not spontaneously or gradually gelate at all, and the silk fragments do not change color or turbidity for at least 10 or 30 days. It is suggested that the claims be amended to clarify whether the time period of 10 or 30 days applies to both gelation and color/turbidity change, or just to color/turbidity change. For the purposes of examination, it is considered that the claim is directed to silk fibroin fragments which do not spontaneously or gradually gelate for at least 10 or 30 days.
Regarding claim 35, the claim recites “a 5% crystalline portion and a 90% amorphous region”. It appears that this should instead be 5% crystalline and 95% amorphous region, for a total of 100%. However, this is unclear from the claim as currently written.
Claims 31-34 and 36-42 are included in this rejection because they depend on a rejected claim and do not clarify the issue.
Claim Rejections - 35 USC § 103
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 30-43 are rejected under 35 U.S.C. 103 as being unpatentable over Kaplan et al., WO 2014/059245 (filed 10/11/2013); in view of Wang et al., Biomacromolecules; 14(1):285-9 (cited in IDS 1/17/2025) and Kim et al., Biomacromolecules; 5(3):786-92; and as evidenced by Romer et al., Prion; 2(4):154-61.
Regarding claim 30, Kaplan teaches silk-based drug delivery compositions (Kaplan p. 1 para. 2). Kaplan teaches that the silk fibroin in the composition may exist in varying degrees of crystallinity (Kaplan p. 14 para. 54; p. 15 para. 60). It is considered that “substantially solid” would include a composition wherein the silk fibroin is all or partially crystalline, as the crystalline form is a solid. Kaplan teaches that the silk fibroin is substantially depleted of sericin (Kaplan p. 7 para. 30).
Kaplan teaches a composition comprising silk fibroin fragments, wherein the silk fibroin fragments have a molecular weight in a range of 3.5 kDa to 300 kDa (Kaplan p. 6 para. 29). Kaplan teaches that molecular weight can be the peak average molecular weight (Mp), the
number average molecular weight (Mn), or the weight average molecular weight (Mw) (Kaplan p. 6 para. 28). When claimed ranges "overlap or lie inside the ranges disclosed by the prior art" and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists. See MPEP 2144.05(I).
Regarding the limitation “wherein the silk fibroin protein fragments, when in a solution, form a substantially homogeneous solution comprising between 0 ppm to about 500 ppm of inorganic residuals and between 0 ppm to about 500 ppm of organic residuals”, this is a functional limitation of the claimed silk protein fragments. Any silk fibroin fragments having the same structure as instantly claimed must necessarily have the same functional features. Further, Kaplan teaches that the silk fragments may be dissolved to form an aqueous solution, by removing sericin and dissolving the silk in an aqueous salt solution, such as lithium bromide, lithium thiocyanate, or calcium nitrate (Kaplan p. 7 para. 32). Kaplan teaches that the salt is removed after dissolution (Kaplan pp. 7-8 para. 32). Thus, it is considered that the silk fragments may be completely dissolved, i.e. forming a homogeneous solution, and that inorganic residuals such as salts may be removed. It would have been obvious to remove all or most of the salts, resulting in a solution with 0-500 ppm inorganic residuals. Kaplan further teaches embodiments wherein the silk solution is entirely free of organic solvents, i.e. 0 ppm organic residuals (Kaplan p. 8 para. 34).
Kaplan does not teach that the silk fibroin fragments have a polydispersity of between about 1.5-3.0 (claim 30).
Regarding claim 30, Wang teaches molecular weights and polydispersity of silk fibroin compositions derived from various methods of degumming and dissolution (Wang p. 286 para. 1). Wang teaches that organic solutions of inorganic salts, which are chaotropic solvents, have been extensively used in dissolving silk fiber (Wang p. 288 Section 3.2). Wang teaches that the dissolving process used influences the molecular weight and polydispersity of the silk fibroin, and shows that polydispersity of silk fibroin ranges from 1.6-2.3 (Wang Table 1; p. 288 Section 3.2). Wang teaches that after degumming using Na2CO3 and dissolving with LiBr, the polydispersity of silk fibroin is 2.1 (Wang Table 1).
It would have been obvious for a skilled artisan to obtain a composition comprising silk fibroin fragments as taught by Kaplan, wherein the silk fibroin fragments have a polydispersity in the range of 1.5-3.0.
As taught by Wang, molecular weights and polydispersity are dependent upon methods used for degumming and dissolution of the silk fibroin. Further, Wang teaches that silk fibroin has a polydispersity of 2.1 after degumming using Na2CO3 and dissolving with LiBr (Wang Table 1). Kaplan teaches the use of these same reagents for degumming and dissolving the silk fibroin fragments (Kaplan p. 7 para. 32). Thus, it is expected that the silk fibroin fragments of Kaplan, prepared using the same reagents as taught by Wang, would have a polydispersity in the range of 1.5-3.0 as instantly claimed.
Kaplan does not teach that the silk fibroin fragments do not spontaneously or gradually gelate and do not visibly change color or turbidity for at least 10 days or at least 30 days (claims 30, 43).
Regarding claims 30 and 43, Kim teaches that the gelation of silk fibroin depends on several factors including fibroin concentration, temperature, ion concentration, and pH (Kim p. 786 para. 3). Kim teaches gelation times of silk fibroin, ranging from 0-60 days depending on various parameters (Kim Figs. 2-5). Kim teaches that the color changes to opaque white when the silk fibroin gelates (Kim p. 787 “Sol-Gel Transitions”).
The limitations “do not spontaneously or gradually gelate and do not visibly change color or turbidity” are functional limitations of the claimed composition, and it is expected that any silk fibroin fragments having the same structure as instantly claimed must necessarily have the same functional features. Further, it would have been obvious for a skilled artisan to obtain a composition comprising silk fibroin fragments as taught by Kaplan, wherein the silk fibroin fragments do not spontaneously or gradually gelate and do not visibly change color or turbidity for at least 10 days or at least 30 days, in view of the teachings of Kim. Kim teaches that gelation and associated color change of silk fibroin is dependent upon various parameters such as temperature, pH, and concentration of silk. Kim teaches multiple examples wherein gelation of silk fibroin takes 10 days or more, or 30 days or more (see Kim Figs. 2-5).
Based on the teachings of Kim, it is clear that parameters influencing gelation time would have been routinely optimized by a skilled artisan. Kim teaches concentrations, temperatures, and pH conditions that are effective to achieve gelation times of at least 10 days or at least 30 days. That means the conditions necessary to achieve gelation of silk fibroin are result-effective variables. Result-effective variables would be optimized through routine experimentation by one having ordinary skill in the art. It would have been obvious for a skilled artisan to optimize conditions including pH, temperature, and silk fibroin concentration to achieve the desired properties of the silk fibroin composition, depending on the desired end use of the composition. Additionally, Kaplan teaches that various factors including pH and temperature can be modified to allow for different conformations of silk fibroin (Kaplan p. 14 para. 54). Thus, it is considered obvious for a skilled artisan to utilize conditions which would prevent spontaneous gelation of the silk fibroin fragments, and as a result prevent color change and turbidity change associated with gelation, for a period of at least 10 days or at least 30 days.
Regarding claims 31-32, Kaplan teaches that the silk fibroin can comprise beta-sheet crystallinity content of at least about 5%, at least about 10%, at least about 20%, at least about 30%, at least about 40%, or at least about 50% (Kaplan p. 15 para. 60).
Regarding claim 33, Kaplan teaches that the silk fibroin comprises a crystallinity content of at least about 50% (Kaplan p. 15 para. 60). Thus, Kaplan teaches a silk fibroin protein fragment wherein the crystalline protein is about one half and the amorphous region is about one half.
Regarding claims 34-35, Kaplan teaches that the crystalline portion can be from at least about 5% to at least about 95% (Kaplan p. 15 para. 60). Thus, Kaplan teaches a ratio of crystalline portion to amorphous region within the range of 99% crystalline to 1% amorphous and 1% crystalline to 99% amorphous.
Regarding claim 36-37, Kaplan teaches that the concentration of silk fibroin in the composition may be about 30% (w/v), about 32.5% (w/v), about 35% (w/v), about 37.5% (w/v), about 40% (w/v), about 42.5% (w/v), about 45% (w/v), about 47.5% (w/v), or about 50% (w/v) (Kaplan p. 9 para. 35).
Regarding claims 38-39, Kaplan teaches that the concentration of silk fibroin may be from about 1 % (w/v) to about 30% (w/v) (Kaplan p. 8 para. 35).
Regarding claim 40, Kaplan teaches that the composition may be water annealed (Kaplan p. 14 para. 54).
Regarding claim 41, Kaplan teaches that the composition comprises a therapeutic agent (Kaplan p. 14 para. 53-54).
Regarding claim 42, Kaplan teaches that the silk fibroin is spider silk protein (Kaplan p. 5 para. 27). Spider silk fibers are known to be hypoallergenic (see Romer “Abstract”).
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 30-43 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 11857664. Although the claims at issue are not identical, they are not patentably distinct from each other because both are directed to substantially solid composition comprising silk fibroin protein fragments.
Regarding claim 30, claim 1 of ‘664 recites: a substantially solid composition comprising silk fibroin protein fragments that are substantially devoid of sericin, the silk fibroin protein fragments having an average weight average molecular weight selected from about 17 kDa to about 38 kDa, about 35 kDa to about 40 kDa, about 40 kDa to about 45 kDa, about 45 kDa to about 50 kDa, about 50 kDa to about 55 kDa, or about 39 kDa to about 80 kDa, and a polydispersity of about 1.5 to about 3.0, wherein the silk fibroin protein fragments, when in a solution form a substantially homogeneous solution comprising between 0 ppm to about 500 ppm of inorganic residuals and between 0 ppm to about 500 ppm of organic residuals, and do not spontaneously or gradually gelate and do not visibly change in color or turbidity for at least 10 days.
The difference between instant claim 30 and claim 1 of ‘664 is the average molecular weights of silk fibroin. However, it would have been obvious for a skilled artisan to optimize the molecular weight of fibroin to achieve the necessary structure depending on the desired use of the composition. Thus, the invention of instant claim 30 is an obvious variation of the invention of ‘664.
Regarding claims 31-43, the limitations of these dependent claims are recited in claims 2-15 of ‘664.
Claims 30, 36-39, and 41-43 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of U.S. Patent No. 11298311. Although the claims at issue are not identical, they are not patentably distinct from each other because both are directed to substantially solid composition comprising silk fibroin protein fragments.
Regarding claim 30, claim 1 of ‘311 recites a composition comprising silk fibroin protein fragments having an average weight average molecular weight selected from 40 kDa to 45 kDa, from 45 kDa to 50 kDa, or from 50 kDa to 55 kDa, and a polydispersity from about 1.5 to about 3.0, wherein:
the silk fibroin protein fragments are substantially devoid of sericin;
the composition is substantially homogeneous;
the composition includes between 0 ppm to about 500 ppm of inorganic residuals and between 0 ppm to about 500 ppm of organic residuals;
and the composition does not spontaneously or gradually gelate and does not visibly change in color or turbidity when in a solution for at least 10 days.
The difference between instant claim 30 and claim 1 of ‘311 is the average molecular weights of silk fibroin. However, it would have been obvious for a skilled artisan to optimize the molecular weight of fibroin to achieve the necessary structure depending on the desired use of the composition. Thus, the invention of instant claim 30 is an obvious variation of the invention of ‘311.
Regarding claims 36-39 and 41-43, the limitations of these dependent claims are recited in claims 2-12 of ‘311.
Conclusion
Claims 30-43 are rejected. No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to EMILY F EIX whose telephone number is (571)270-0808. The examiner can normally be reached M-F 8am-5pm ET.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sharmila Landau can be reached at (571)272-0614. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/EMILY F EIX/
Examiner, Art Unit 1653
/SHARMILA G LANDAU/Supervisory Patent Examiner, Art Unit 1653
Prosecution Insights