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 and Claim Status
Applicant’s election without traverse of Group 1 in the reply filed on 6/20/25 is acknowledged.
Claims 11-20 are to a non-elected group.
Claims 11-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 6/20/25.
Claims 1-10 are being examined.
Claims 1-10 are rejected.
Priority
This application, filed 02/07/2022, is a Continuation of 16324844 , filed 02/11/2019 ,now U.S. Patent # 11242367 and having 1 RCE-type filing therein
16324844 is a National Stage entry of PCT/US2017/046659 , International Filing Date: 08/12/2017
PCT/US2017/046659 Claims Priority from Provisional Application 62467697 , filed 03/06/2017
PCT/US2017/046659 Claims Priority from Provisional Application 62407863 , filed 10/13/2016
PCT/US2017/046659 Claims Priority from Provisional Application 62374532 , filed 08/12/2016.
Information Disclosure Statement
The Examiner has considered the reference(s) provided in the 5/5/22 and 3/13/23 Information Disclosure Statement, except as crossed through, and provides a signed and dated copy of each herewith.
-Claim Interpretation
The claims limitations are given their broadest reasonable interpretation (BRI), (“[T]he ordinary and customary meaning of a claim term is the meaning that the term would have to a person of ordinary skill in the art in question at the time of the invention, i.e., as of the effective filing date of the patent application.” Phillips v. AWH Corp., 75 USPQ2d 1321, 1326 (Fed. Cir. 2005) (en banc).) The broadest reasonable interpretation of the claims must also be consistent with the interpretation that those skilled in the art would reach.” MPEP 2111, with reference to In re Cortright, 49 USPQ2d 1464, 1468. The claim limitations are given their BRI consistent with the specification, MPEP 2111, and under the BRI, words of the claim must be given their plain meaning, unless such meaning is inconsistent with the specification, MPEP 2111.01.
The specification states the following with regard to “about”:
[0043] The term “about” can refer to a variation of ±5%, ±10%, ±20%, or ±25% of the value specified. For example, “about 50” percent can in some embodiments carry a variation from 45 to 55 percent. For integer ranges, the term “about” can include one or two integers greater than and/or less than a recited integer at each end of the range. Unless indicated otherwise herein, the term “about” is intended to include values, e.g., weight percentages, proximate to the recited range that are equivalent in terms of the functionality of the individual ingredient, element, the composition, or the embodiment. The term about can also modify the end-points of a recited range as discuss above in this paragraph.
Based on the above, “about” is interpreted broadly and can extend the range of a claimed “about [value]” by up to over and less than 25% of the value. For example, the “about 60 kDa” limitation in claim 1 is interpreted to encompass a molecular weight anywhere from 45 to 75 kDa, inclusive of these endpoint values. Also as an example, claim 3’s about 39% when extended by up to over and less than 25% of the value results in a percentage value range of 29.25% to 48.75%. The same approach applies to other values in the claims.
Claim Rejections - 35 USC § 102
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 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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1-10 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Abdel-Naby et al. (US 2019/0117834; ‘Abdel-Naby’).
The applied reference has a common inventor with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2). This rejection under 35 U.S.C. 102(a)(2) might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C. 102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B) if the same invention is not being claimed; or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed in the reference and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement.
Abdel-Naby teach silk derived protein compositions (abstract and claims). Abdel-Naby recite fibroin-derived protein compositions (claim 1) that possess enhanced stability in an aqueous solution (claim 5) wherein the primary amino acid sequence of the fibroin-derived protein composition differ from native fibroin by at least 4% with respect to the combined amino acid content of serine, glycine and alanine (claim 2); cysteine disulfide bonds between the fibroin heave and fibroin light protein chains are reduced or eliminated (claim 4); a plurality of the peptide chains in the protein composition terminate in amide groups (claim 1); the composition has a serine content that is reduced by greater than 40% compared to native fibroin protein wherein the serine content is at least about 5% (claim 3) and wherein the average molecular weight of the fibroin-derived protein composition is between about 30kDa and 60kDa (claim 8). Abdel-Naby specifically teach preparing silk-derived protein including autoclaving in a 54 wt% LiBr solution (example 1 page 15 specifically section 0140). Abdel-Naby teach that the silk solution was further purified and figure 5C shows a fractionated solution predominantly in the 30 kDa range (example 5 page 18 section 0160 of Abdel-Naby and figure 1C of 62/320,177).
The instant claims recite numerous properties. The Patent Office does not have the facilities to test the composition prepared by Abdel-Naby (example 5 figure 5c). The instant specification recites processes (page 31 and 41). Since Abdel-Naby teach the same processes (example 1 page 15 specifically section 0140 and example 5 page 18 section 0160) and also recite features as claimed (claims 1-5) there is a reasonable bases that the claim limitations are met. Thus the claim limitations are met absent evidence to the contrary (see MPEP 2112 V and MPEP 2112.01 II).
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.
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 1-10 is/are rejected under 35 U.S.C. 103 as being obvious over Abdel-Naby et al. (US 2019/0117834; ‘Abdel-Naby’).
The applied reference has a common inventor with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
Abdel-Naby teach silk derived protein compositions (abstract and claims). Abdel-Naby recite fibroin-derived protein compositions (claim 1) that possess enhanced stability in an aqueous solution (claim 5) wherein the primary amino acid sequence of the fibroin-derived protein composition differ from native fibroin by at least 4% with respect to the combined amino acid content of serine, glycine and alanine (claim 2); cysteine disulfide bonds between the fibroin heave and fibroin light protein chains are reduced or eliminated (claim 4); a plurality of the peptide chains in the protein composition terminate in amide groups (claim 1); the composition has a serine content that is reduced by greater than 40% compared to native fibroin protein wherein the serine content is at least about 5% (claim 3) and wherein the average molecular weight of the fibroin-derived protein composition is between about 30kDa and 60kDa (claim 8). Abdel-Naby specifically teach preparing silk-derived protein including autoclaving in a 54 wt% LiBr solution (example 1 page 15 specifically section 0140). Abdel-Naby teach that the silk solution was further purified and figure 5C shows a fractionated solution predominantly in the 30 kDa range (example 5 page 18 section 0160 of Abdel-Naby and figure 1C of 62/320,177).
Abdel-Naby suggest obtaining low molecular weight fragments (abstract) and suggest fragments of various sizes including less than about 20 kDa or less than about 10 kDa (section 0149) where the fragments have advantageous properties including increased cell migration, proliferation and wound closure rate (section 0149) but does not teach a specific example of preparing less than about 10 kDa fractions.
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the teachings of Abdel-Naby because Abdel-Naby suggest obtaining low molecular weight fragments (abstract) and suggest that fragments of various sizes including less than about 20 kDa or less than about 10 kDa (section 0149) where the fragments have advantageous properties including increased cell migration, proliferation and wound closure rate (section 0149). Thus one would have been motivated to optimize the size of the fragments used (MPEP 2144.05 II), and further in this regard Abdel-Naby also specifically claims molecular weight ranges that fall within or overlap the instantly claimed ranges, see Abdel-Naby claims 11-14 and also claim 15, which also directs one of ordinary skill in the art to include a portion of relatively higher molecular weight SDP fragments than those less than about 20 kDa or less than about 10 kDa. Since Abdel-Naby teach that the general methods of preparation were known (example 1 page 15 and example 5 page 18) one would have had a reasonable expectation of success.
In relation to instant claim 1, Abdel-Naby recite fibroin-derived protein compositions (claim 25) that possess enhanced stability in an aqueous solution (claim 5) wherein the primary amino acid sequence of the fibroin-derived protein composition differ from native fibroin by at least 4% with respect to the combined amino acid content of serine, glycine and alanine (claim 2); cysteine disulfide bonds between the fibroin heavy and fibroin light protein chains are reduced or eliminated (claim 4); a plurality of the peptide chains in the protein composition terminate in amide groups (claim 1); the composition has a serine content that is reduced by greater than 40% compared to native fibroin protein wherein the serine content is at least about 5% (claim 3). Abdel-Naby suggest obtaining low molecular weight fragments (abstract) and suggest that fragments of various sizes including less than about 20 kDa or less than about 10 kDa (section 0149).
In relation to claim 2, Abdel-Naby suggest obtaining low molecular weight fragments (abstract) and suggest fragments of various sizes including less than about 20 kDa or less than about 10 kDa (section 0149).
In relation to claim 3, Abdel-Naby suggest compositions that do not gel after ultrasonication (sections 0016 and 0075).
In relation to claims 4-6, Abdel-Naby specifically teach serine, glycine and alanine (claim 2) so one would have been motivated to optimize the amounts. Further, the instant specification recites processes (page 31 and 41). Since Abdel-Naby teach the same processes (example 1 page 15 specifically section 0140 and example 5 page 18 section 0160) and also recite features as claimed (claims 1-5) there is a reasonable bases that the claim limitations are met.
In relation to claim 7, Abdel-Naby teach that the composition can completely redissolve after being dried to a thin film (section 0079).
In relation to claim 8, Abdel-Naby teach compositions that lack beta-sheet protein structure (section 0079).
In relation to claim 9, Abdel-Naby teach compositions that maintain an optical absorbance in aqueous solution of less than 0.25 at 550 nm after at least five seconds of ultrasonication (section 0079).
In relation to claim 10, Abdel-Naby teach compositions formulated as an aqueous solution (claim 25).
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 §§ 706.02(l)(1) - 706.02(l)(3) 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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1-10 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 11242367 (issued parent of instant application). Although the claims at issue are not identical, they are not patentably distinct from each other.
The 367 claims compositions are directed to a narrower subgenus of fibroin-derived protein than what is instantly claimed, particularly when considering the up to +/-25% allowed variation based on “about” in the instant claims and that the same process results in the same product, including all of its properties.
As to any differences even assuming less variation of any value based on “about”, MPEP 2144.05 recognizes that where the claimed ranges overlap with the ranges of the prior art that a prima facie case of obviousness exists. In the instant case, one would have been motivated to optimize the molecular weight range because 367 recites specific properties (enhanced stability of claim 1) associated with the compositions.
Considering the 367 claims 1, 3 and 7, and instant claims 1 and 5, the serine content range overlaps and the lacking beta-sheet protein structure in aqueous solution is met by the 367 claims. Instant claim 1 accordingly is rejected under this section.
In relation to instant claims 2 and 3, and given that per 367 claim 1 “39%+/−10% of the protein chains of the protein composition have a molecular weight within the range of 25 kDa to 50 kDa” the MW limitations of instant claims 2 and 3 would have been met by a range of embodiments encompassed by 367 claim 1, particularly those embodiments with 39%-10% having a molecular weight of 25 kDa, so claims 2 and 3 are rejected under this section.
In relation to instant claim 4, this is rejected over 367 claims 1 and 2.
In relation to instant claim 5, this is addressed above.
In relation to instant claim 6, this is rejected over 367 claim 4.
In relation to instant claim 7, this is rejected over 367 claim 5.
In relation to instant claim 8, this is rejected over 367 claim 6.
In relation to instant claim 9, this is rejected over 367 claim 8.
In relation to instant claim 10, this is rejected over 367 claim 9.
Claims 1-7, 10 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 11890328 (‘328’) in view of U.S. Patent No. 10953132 (‘132’).
The 328 claim 1 is directed to method of treating dry eye syndrome in a subject comprising administering an effective amount of a protein composition to an eye of the subject, thereby treating the dry eye disease, wherein the protein composition is formulated as an ophthalmic formulation comprising water; wherein the protein composition is a fibroin-derived protein composition prepared by a process comprising heating an aqueous fibroin solution at an elevated pressure, wherein: the aqueous fibroin solution comprises lithium bromide at a concentration of at least about 8M, and the aqueous fibroin solution is heated to at least about 105° C. (221° F.) under a pressure of about 10 PSI to about 20 PSI for at least about 20 minutes in the presence of the lithium bromide; to provide a protein composition comprising fibroin-derived protein wherein: the primary amino acid sequences of the fibroin-derived protein composition differ from native fibroin by at least by at least 4% with respect to the combined amino acid content of serine, glycine, and alanine, based on the combined absolute values of the differences in the content of serine, glycine, and alanine; cysteine disulfide bonds between the fibroin heavy and fibroin light protein chains of fibroin are reduced or eliminated; the protein composition has a serine content that is reduced by greater than 25% compared to native fibroin protein; and wherein the average molecular weight of the fibroin-derived protein composition is less than about 100 kDa.
The 328 claim 6 is directed to the method of claim 1 wherein the fibroin-derived protein has an average molecular weight of less than about 60 kDa, so meeting instant claim 1’s upper bound MW limitation.
The 328 claim 9 is directed to the method of claim 1 wherein the fibroin-derived protein comprises between 4.5% and 7.5% serine amino acid residues, so meeting instant claim 1’s serine limitation.
As to lacking beta-sheet structure in aqueous solution, absent evidence to the contrary this is an inherent property of the composition set forth in the referred to claims of the cited reference based on having the same or similarly modified amino acid composition and process treatments to obtain these.
As to the lower MW limitation of instant claim 1, the 132, directed to and claiming fibroin-derived protein also, however in its claim 1 method for treating an ocular wound, sets forth similar limitations for its silk fibroin-derived protein (SDP) fragments, and includes these having an average molecular weight between about 30 kDa and 60 kDa. For the motivation to improve the claimed subject matter of the 328, including when used for its method of treating dry eye syndrome, given that the 132 claim 1 is directed to a method for treating an ocular wound so it expected to be effective, one of ordinary skill in the art would have been motivated to further limit the molecular weight of the 328 claim 1 to conform with that of the 132 in its claim 1. The level of ordinary skill in the art is high, and there would have been a reasonable expectation of success given the claims and teachings and examples of the ‘132. With regard to embodiments of the 132 MW range meeting instant claim 1’s “wherein greater than 50% of the protein chains of the protein composition have a molecular weight of less about 60 kDa”, this is based on the arithmetic relationship between number of particles and their average: to get to 30 kDa average there cannot be too many very high MW protein chains to be included into the averaging, these being balanced against smaller particles that each contribute less to the total weight. Absent evidence to the contrary, based on the need to balance weights of individual SDP fragments to meet an average MW around 30 kDa, embodiments of the 132 claim 1 where the average MW is around 30 kDa would meet instant claim 1’s “wherein greater than 50% of the protein chains of the protein composition have a molecular weight of less about 60 kDa”. Accordingly instant claim 1 is rejected under this section.
In relation to instant claims 2 and 3, the MW of the 132, particularly when considering the make-up of protein fragments contributing to obtain an average molecular weight of or around 30 kDa, see analysis above, reasonably results in embodiments that fall within the MW limitations of instant claims 2 and 3, so instant claims 2 and 3 are rejected under this section.
In relation to instant claim 4, this is suggested by the low viscosity limitation of the 328 claim 7.
In relation to instant claim 5, this is met by the 328 claim 9, see also claim 12.
In relation to instant claim 6, this is rejected over 328 claim 13.
In relation to instant claim 7, this is rejected over 328 claim 15.
In relation to instant claim 10, this is rejected over 328 claim 1 (explicit as to water).
Claims 1-10 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of U.S. Patent No. 9,394,355. Although the claims at issue are not identical, they are not patentably distinct from each other.
355 claim 1 claims fibroin-derived protein compositions that possess enhanced stability in an aqueous solution wherein the primary amino acid sequence of the fibroin-derived protein composition differ from native fibroin by at least 6% with respect to the combined amino acid content of serine, glycine and alanine; cysteine disulfide bonds between the fibroin heave and fibroin light protein chains are reduced or eliminated; a plurality of the peptide chains in the protein composition terminate in amide groups; the composition has a serine content that is reduced by greater than 40% compared to native fibroin protein wherein the serine content is at least about 5% and wherein the average molecular weight of the fibroin-derived protein composition is less than about 60kDa and greater than about 30kDa (claim 1). 355 recites that the composition does not gel upon ultrasonication of an aqueous solution of the protein composition at concentrations of up to 10% w/w (claim 5). 355 recites that there are specific amounts of serine, glycine and alanine (claims 6-11). 355 recites that the protein composition re-dissolves in water after being dried to a thin film (claim 12). 355 recites that the protein composition lacks beta-sheet protein structure in aqueous solution (claim 13). 355 recites that the protein composition maintains an optical absorbance in aqueous solution of less than 0.25 at 550 nm after at least five seconds of ultrasonication (claim 14). 355 recites composition in water (claim 2).
Since 355 recites the average molecular weight of the fibroin-derived protein composition is less than about 60kDa and greater than about 30kDa (claim 1) one would have made such compositions (see MPEP 2131.03). Further, MPEP 2144.05 recognizes that where the claimed ranges overlap with the ranges of the prior art that a prima facie case of obviousness exists. In the instant case, one would have been motivated to optimize the molecular weight range because 355 recites specific properties (enhanced stability of claim 1) associated with the compositions.
In relation to instant claim 1, 355 recites fibroin-derived protein compositions that possess enhanced stability in an aqueous solution wherein the primary amino acid sequence of the fibroin-derived protein composition differ from native fibroin by at least 6% with respect to the combined amino acid content of serine, glycine and alanine; cysteine disulfide bonds between the fibroin heave and fibroin light protein chains are reduced or eliminated; a plurality of the peptide chains in the protein composition terminate in amide groups; the composition has a serine content that is reduced by greater than 40% compared to native fibroin protein wherein the serine content is at least about 5% and wherein the average molecular weight of the fibroin-derived protein composition is less than about 60kDa and greater than about 30kDa (claim 1). Further as to meeting the lacking beta-sheet structure in aqueous solution limitation, absent evidence to the contrary this is an inherent property of the composition set forth in the referred to claims of the cited reference based on having the same or similarly modified amino acid composition and process treatments to obtain these.
In relation to instant claims 2 and 3, 355 recites the average molecular weight of the fibroin-derived protein composition is less than about 60kDa and greater than about 30kDa (claim 1). When considering the make-up of protein fragments contributing to obtain an average molecular weight of or around 30 kDa, it is very reasonable that embodiments fall within the MW limitations of instant claims 2 and 3 and therefore are the basis for rejection of these claims under this section. That is, given the inclusion of the average molecular weight being as low as 30 kDa, it is very reasonable to expect that for many embodiments that fall within the 355 claim 1 where the average MW is around 30 kDa, that these embodiments would clearly meet not only instant claim 1’s “wherein greater than 50% of the protein chains of the protein composition have a molecular weight of less about 60 kDa” but also the limitations of instant claims 2 and 3. This is based on the arithmetic relationship between number of particles and their average: to get to 30 kDa average there cannot be too many very high MW protein chains to be included into the averaging, these being balanced against smaller particles that each contribute less to the total weight. Absent evidence to the contrary, based on the need to balance weights of individual SDP fragments to meet an average MW around 30 kDa, embodiments of the 355 claim 1 where the average MW is around 30 kDa would meet instant claim 1’s “wherein greater than 50% of the protein chains of the protein composition have a molecular weight of less about 60 kDa”, and also the limitations of instant claims 2 and 3.
In relation to claim 4, 355 recites that the composition does not gel upon ultrasonication of an aqueous solution of the protein composition at concentrations of up to 10% w/w (claim 5).
In relation to claims 5-7, 355 recites that there are specific amounts of serine, glycine and alanine (claims 6, 8 and 10).
In relation to claim 8, 355 recites that the protein composition re-dissolves in water after being dried to a thin film (claim 12).
In relation to claim 9, 355 recites that the protein composition maintains an optical absorbance in aqueous solution of less than 0.25 at 550 nm after at least five seconds of ultrasonication (claim 14).
In relation to claim 10, 355 recites composition in water (claim 2).
Claims 1-10 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 9,907,836 (‘836’). Although the claims at issue are not identical, they are not patentably distinct from each other.
836 recites fibroin-derived protein compositions comprising water wherein the primary amino acid sequence of the fibroin-derived protein composition differ from native fibroin by at least 6% with respect to the combined amino acid content of serine, glycine and alanine; cysteine disulfide bonds between the fibroin heavy and fibroin light protein chains are reduced or eliminated; a plurality of the peptide chains in the protein composition terminate in amide groups; the composition has a serine content that is reduced by greater than 40% compared to native fibroin protein and wherein the average molecular weight of the fibroin-derived protein composition is less than about 60kDa (claim 1). 836 recites that the composition does not gel upon ultrasonication of an aqueous solution of the protein composition at concentrations of up to 10% w/w (claim 9). 836 recites that there are specific amounts of serine, glycine and alanine (claims 10-12). 836 recites that the protein composition maintains an optical absorbance in aqueous solution of less than 0.25 at 550 nm after at least five seconds of ultrasonication (claim 13).
Since 836 recites specific serine concentrations (claim 10) one would have been motivated to make compositions with such concentrations. Since 836 recite the average molecular weight of the fibroin-derived protein composition is less than about 60kDa (claim 1) one would have made such compositions (see MPEP 2131.03). Further, MPEP 2144.05 recognizes that where the claimed ranges overlap with the ranges of the prior art that a prima facie case of obviousness exists. In the instant case, one would have been motivated to optimize the molecular weight range because 836 recites specific properties (claim 9) associated with the compositions.
In relation to instant claim 1, 836 recites fibroin-derived protein compositions comprising water wherein the primary amino acid sequence of the fibroin-derived protein composition differ from native fibroin by at least 6% with respect to the combined amino acid content of serine, glycine and alanine; cysteine disulfide bonds between the fibroin heavy and fibroin light protein chains are reduced or eliminated; a plurality of the peptide chains in the protein composition terminate in amide groups; the composition has a serine content that is reduced by greater than 40% compared to native fibroin protein and wherein the average molecular weight of the fibroin-derived protein composition is less than about 60kDa (claim 1). Further, 836 recites specific serine concentrations (claim 10). Although 836 does not recite ‘possesses enhanced stability’, 836 recite or suggest the claim composition so the composition would have the features claimed (MPEP 2112.01 II). Further in this regard as to the lacking beta-sheet structure in aqueous solution limitation in instant claim 1, absent evidence to the contrary this is an inherent property of the composition set forth in the referred to claims of the cited reference based on having the same or similarly modified amino acid composition and process treatments to obtain these. Further, 836 recites the inclusion of a stabilizing agent (claim 3).
In relation to instant claim 2, 836 recites that the average molecular weight of the fibroin-derived protein composition is less than about 60kDa (claim 1).
In relation to instant claim 3, 836 recites that the composition does not gel upon ultrasonication of an aqueous solution of the protein composition at concentrations of up to 10% w/w (claim 9).
In relation to claims 4-6, 836 recites that there are specific amounts of serine, glycine and alanine (claims 10-12).
In relation to claims 7-8, 836 recites or suggest the claimed composition so the composition would have the features claimed (MPEP 2112.01 II).
In relation to claim 9, 836 recites that the protein composition maintains an optical absorbance in aqueous solution of less than 0.25 at 550 nm after at least five seconds of ultrasonication (claim 13).
In relation to claim 10, 836 recites fibroin-derived protein compositions comprising water (claim 1)
Claims 1-10 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 10,471,128 ( ‘128’). Although the claims at issue are not identical, they are not patentably distinct from each other.
128 claims fibroin-derived protein compositions that possess enhanced stability in an aqueous solution wherein the primary amino acid sequence of the fibroin-derived protein composition differ from native fibroin by at least 4% with respect to the combined amino acid content of serine, glycine and alanine; cysteine disulfide bonds between the fibroin heave and fibroin light protein chains are reduced or eliminated; a plurality of the peptide chains in the protein composition terminate in amide groups (claim 11); the composition has a serine content that is reduced by greater than 25% compared to native fibroin protein and wherein the average molecular weight of the fibroin-derived protein composition is 18.75 kDa to about 100 kDa (claim 1). As to lacking beta-sheet structure in aqueous solution, absent evidence to the contrary this is an inherent property of the composition set forth in the referred to claims of the cited reference based on having the same or similarly modified amino acid composition and process treatments to obtain these. 128 recites that the composition does not gel upon ultrasonication of an aqueous solution of the protein composition at concentrations of up to 10% w/w (claim 4). 128 recites that there are specific amounts of serine, glycine and alanine (claims 5-10). 128 recites that the protein composition re-dissolves in water after being dried to a thin film (claim 12). 128 recites that the protein composition lacks beta-sheet protein structure in aqueous solution (claim 13). 128 recites that the protein composition maintains an optical absorbance in aqueous solution of less than 0.25 at 550 nm after at least five seconds of ultrasonication (claim 14). 128 recites composition in water (claim 15).
Since 128 recites the average molecular weight of the fibroin-derived protein composition is 18.75 kDa to about 100 kDa (claim 1) one would have made such compositions (see MPEP 2131.03). Further, MPEP 2144.05 recognizes that where the claimed ranges overlap with the ranges of the prior art that a prima facie case of obviousness exists. In the instant case, one would have been motivated to optimize the molecular weight range because 128 recites specific properties (enhanced stability in claim 1) associated with the compositions.
In relation to instant claim 1, 128 recites fibroin-derived protein compositions that possess enhanced stability in an aqueous solution wherein the primary amino acid sequence of the fibroin-derived protein composition differ from native fibroin by at least 4% with respect to the combined amino acid content of serine, glycine and alanine; cysteine disulfide bonds between the fibroin heave and fibroin light protein chains are reduced or eliminated; a plurality of the peptide chains in the protein composition terminate in amide groups (claim 11); the composition has a serine content that is reduced by greater than 25% compared to native fibroin protein and wherein the average molecular weight of the fibroin-derived protein composition is 18.75 kDa to about 100 kDa (claim 1).
In relation to instant claim 2, 128 recites the average molecular weight of the fibroin-derived protein composition is 18.75 kDa to about 100 kDa (claim 1).
In relation to instant claim 3, 128 recites that the composition does not gel upon ultrasonication of an aqueous solution of the protein composition at concentrations of up to 10% w/w (claim 4).
In relation to instant claims 4-6, 128 recites that there are specific amounts of serine, glycine and alanine (claims 5-10).
In relation to instant claim 7, 128 recites that the protein composition re-dissolves in water after being dried to a thin film (claim 12).
In relation to instant claim 8, 128 recites that the protein composition lacks beta-sheet protein structure in aqueous solution (claim 13).
In relation to instant claim 9, 128 recites that the protein composition maintains an optical absorbance in aqueous solution of less than 0.25 at 550 nm after at least five seconds of ultrasonication (claim 14).
In relation to instant claim 10, 128 recites composition in water (claim 15).
Claims 1-10 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 11045524 (reference patent; ‘524’), in view of U.S. Patent No. 10953132 (‘132’).
The 524 claim 1 claims “A fibroin-derived protein composition that possesses enhanced stability in an aqueous solution, wherein: the primary amino acid sequences of the fibroin-derived protein composition differ from native fibroin by at least 6% with respect to the combined amino acid content of serine, glycine, and alanine, based on the combined absolute values of the differences in the content of serine, glycine, and alanine; cysteine disulfide bonds between the fibroin heavy and fibroin light protein chains of fibroin are reduced or eliminated; the protein composition has a serine content that is reduced by greater than 25% compared to native fibroin protein, and the protein composition comprises between 4.5% and 7.5% serine amino acid residues; wherein the average molecular weight of the fibroin-derived protein composition is less than about 100 kDa; and wherein the protein composition has an aqueous viscosity of less than 4 cP as a 10% w/w solution in water” but does not claim a lower limit or range of the average molecular weight of the fibroin-derived protein composition. The 524 claim 11 meets this same limitation in instant claim 1.
The 132, directed to and claiming fibroin-derived protein also, however in its claim 1 method for treating an ocular wound, sets forth similar limitations for its silk fibroin-derived protein (SDP) fragments, and includes these having an average molecular weight between about 30 kDa and 60 kDa. For the purposes of improving the claimed subject matter of the 524, including when it is used in an ophthalmic formulation per its claim 14, it would have been obvious to one of ordinary skill in the art to further limit the molecular weight to conform with that of the 132 in its claim 1, at least given that the latter was used for treating an ocular wound. As to lacking beta-sheet structure in aqueous solution, absent evidence to the contrary this is an inherent property of the composition set forth in the referred to claims of the cited reference, and including the narrower MW range of the 132, based on having the same or similarly modified amino acid composition and process treatments to obtain these.
The level of ordinary skill in the art is high, and there would have been a reasonable expectation of success given the claims and teachings and examples of the ‘132. Accordingly the 524 instant claim 1 is rejected under this section.
In relation to instant claims 2 and 3, the MW of the 132, particularly when considering the make-up of protein fragments contributing to obtain an average molecular weight of or around 30 kDa, reasonably results in embodiments that fall within the MW limitations of instant claims 2 and 3. That is, given the inclusion of the average molecular weight being as low as 30 kDa, it is very reasonable to expect that for many embodiments that fall within the 132 claim 1 where the average MW is around 30 kDa, that these embodiments would clearly meet instant claim 1’s “wherein greater than 50% of the protein chains of the protein composition have a molecular weight of less about 60 kDa” as well as the limitations of instant claims 2 and 3. This is based on the arithmetic relationship between number of particles and their average: to get to 30 kDa average there cannot be too many very high MW protein chains to be included into the averaging, these being balanced against smaller particles that each contribute less to the total weight. Absent evidence to the contrary, based on the need to balance weights of individual SDP fragments to meet an average MW around 30 kDa, embodiments of the 132 claim 1 where the average MW is around 30 kDa would meet instant claim 1’s “wherein greater than 50% of the protein chains of the protein composition have a molecular weight of less about 60 kDa”, and also the limitations of instant claims 2 and 3.
In relation to instant claim 4, this is rejected over 524 claim 4.
In relation to instant claim 5, this is met by the 524 claim 1 range for serine.
In relation to instant claim 6, this is rejected over 524 claim 5.
In relation to instant claim 7, this is rejected over 524 claim 7.
In relation to instant claim 8, this is rejected over 524 claim 10.
In relation to instant claim 9, this is rejected over 524 claim 12.
In relation to instant claim 10, this is rejected over 524 claim 1 (aqueous solution), and also confirmed by claim 2 (explicit as to water).
Claims 1-3, 5-7, 10 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of U.S. Patent No. 10953132 (reference patent; ‘132’). Although the claims at issue are not identical, they are not patentably distinct from each other.
The 132, directed to and claiming fibroin-derived protein, in its claim 1 method for treating an ocular wound, sets forth limitations the same as or similar to instant claim 1 (see below), and for its silk fibroin-derived protein (SDP) fragments includes these having an average molecular weight between about 30 kDa and 60 kDa. This range falls within instant claim 1’s less than about 60 kDa and greater than about 10 kDa, and given the inclusion of the average molecular weight being as low as 30 kDa (or lower when considering the range of “about” defined in its para 19), it is very reasonable to expect that for many embodiments that fall within the 132 claim 1 where the average MW is around 30 kDa, that these embodiments would clearly meet instant claim 1’s “wherein greater than 50% of the protein chains of the protein composition have a molecular weight of less about 60 kDa”. This is based on the arithmetic relationship between number of particles and their average: to get to 30 kDa average there cannot be too many very high MW protein chains to be included into the averaging, these being balanced against smaller particles that each contribute less to the total weight. Absent evidence to the contrary, based on the need to balance weights of individual SDP fragments to meet an average MW around 30 kDa, embodiments of the 132 claim 1 where the average MW is around 30 kDa would meet instant claim 1’s “wherein greater than 50% of the protein chains of the protein composition have a molecular weight of less about 60 kDa”. The same analysis applies to the limitations of claims 2 and 3. As to lacking beta-sheet structure in aqueous solution, absent evidence to the contrary this is an inherent property of the composition set forth in the referred to claims of the cited reference based on having the same or similarly modified amino acid composition and process treatments to obtain these.
Further, 132 recites fibroin-derived protein compositions (claim 1) that possess enhanced stability in an aqueous solution (claim 3) wherein the primary amino acid sequence of the fibroin-derived protein composition differ from native fibroin by at least 4% with respect to the combined amino acid content of serine, glycine and alanine (claim 1); cysteine disulfide bonds between the fibroin heave and fibroin light protein chains are reduced or eliminated (claim 2); a plurality of the peptide chains in the protein composition terminate in amide groups (claim 1); the composition has a serine content that is reduced by greater than 40% compared to native fibroin protein wherein the serine content is at least about 5% (claim 1) and wherein the average molecular weight of the fibroin-derived protein composition is between about 30kDa and 60kDa (as discussed above).
Since 132 recites compositions that are used in a method one would have been motivated to make the compositions. Since 132 recites the average molecular weight of the fibroin-derived protein composition is between about 30 kDa and 60 kDa (claim 8) one would have made such compositions (see MPEP 2131.03). Further, MPEP 2144.05 recognizes that where the claimed ranges overlap with the ranges of the prior art that a prima facie case of obviousness exists. In the instant case, one would have been motivated to optimize the molecular weight range because 132 recites specific uses of the compositions and specific properties (claims 1-3). Further, since 132 recites serine, glycine and alanine in the compositions (claim 1) one would have been motivated to optimize the amounts.
Based on the above, instant claim 1 is rejected under this section.
Further in relation to instant claim 2, 132 claims 7 and 8 overlap what is claimed, and in addition 132 claim 1 recites that the average molecular weight of the fibroin-derived protein composition is between about 30kDa and 60kDa, per the arithmetic calculation per above reasonably meeting the claim 2 limitation.
Further in relation to claim 3, in addition to the above reasoning applied to claim 2, and the Claim Interpretation regarding “about”, 132 recite or suggest the claimed composition so the composition would have the features claimed (MPEP 2112.01 II).
In relation to claims 5-7, 132 recites serine, glycine and alanine in the compositions (claim 1) so one would have been motivated to optimize the amounts, and alternatively 132 claim 1 recites or suggests the claimed composition so the composition would have the features claimed (MPEP 2112.01 II).
In relation to claim 10, 132 recites aqueous compositions (claim 12).
Further as to instant claim 1’s limitations/properties not specified in the 132 claims, the Patent Office does not have the facilities to test the composition claimed in the 132, and given that the 132 and the instant application are directed to preparing the fibroin-derived proteins/fragments using the same processes there is a reasonable bases that the claim limitations are met. Thus the claim limitations not explicitly recited in the 132 claims are met absent evidence to the contrary (see MPEP 2112 V and MPEP 2112.01 II).
Claims 1-7, 10 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, 6, 8 of U.S. Patent No. 12350321 (‘321’) in view of U.S. Patent No. 10953132 (‘132’).
The 321 claim 1 is directed to fibroin-derived protein composition prepared by a process comprising heating an aqueous fibroin solution at an elevated pressure, wherein: the aqueous fibroin solution comprises lithium bromide at a concentration of at least about 8M, and the aqueous fibroin solution is heated to at least about 105° C. (221° F.) under a pressure of about 10 PSI to about 20 PSI for at least about 20 minutes in the presence of the lithium bromide; to provide a protein composition comprising fibroin-d