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 with traverse of Group 2 and the species of (FL)8 in the reply filed on 1/21/26 is acknowledged. The traversal is on the ground(s) that claim 1 refers to a first denaturing step and that the claims refer to an entangled polypeptide.
This is not found persuasive because claims 20-21 for example are product claims and the patentability of a product does not depend on its method of production (MPEP 2113). Claim 20 does not even refer to any particular method of production. Further, references cited below (for example Li et al.) address additional embodiments of the claims. With respect to the word entangled, section 006 on page 2 of the instant specification refers to ‘chains in the network can cross each other, resulting in chain entanglement’. Although unclear (see 112 rejection below), the prior art teachings and suggestions are interpreted as meeting the claim limitations.
The requirement is still deemed proper and is therefore made FINAL.
Claims 19-21, 23-24 and 28-31 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 1/21/26.
Claims to the elected species are rejected as set forth below. Any relevant art that was uncovered during the search for the elected species is cited herein in order to advance prosecution.
Claims 5-6, 9-10, 12-14, 22 and 25-27 have been canceled.
Claims 1-4, 7-8, 11 and 15-18 are being examined.
Priority
This application claims benefit of 63/115,174 11/18/20.
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, or 365(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. 119(e) 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 the first paragraph of 35 U.S.C. 112. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. 63/115,174, fails to provide adequate written description in the manner provided by the first paragraph of 35 U.S.C. 112 for claims 1-4, 7-8, 11 and 15-18 of this application.
Claim 1 broadly recites ‘aqueous environment’ (which is encompassed by all dependent claims) and ‘overlapping polypeptide’. Claim 2 broadly recites ‘chaotropic agent’.
Application No. 63/115,174 does not recite ‘environment’. Application No. 63/115,174 recites ‘water’, but ‘water’ is not necessarily the equivalent or representative of any and all aqueous environments. With respect to ‘overlapping polypeptide’, Application No. 63/115,174 appears to refer to overlap in the context of (FL)8.
Application No. 63/115,174 does not recite ‘chaotropic’. Application No. 63/115,174 recites guanidine hydrochloride, but ‘guanidine hydrochloride’ is not necessarily the equivalent or representative of any and all chaotropic agents.
It is noted that section 2152.01 of the MPEP sets forth the method to determine the effective filing date. In particular, ‘If the application properly claims benefit under 35 U.S.C. 119(e) to a provisional application, the effective filing date is the filing date of the claimed invention is the filing date of the provisional application for any claims which are fully supported under 35 U.S.C. 112 by the provisional application.’. In the instant case, claims 1-4, 7-8, 11 and 15-18 are not fully supported by the provisional Application No. 63/115,174. As such, for purposes of searching for prior art, a priority date of 11/16/21 is used for claims 1-4, 7-8, 11 and 15-18.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 11/26/23, 9/20/24 and 1/21/26 have been considered by the examiner.
Specification
The disclosure is objected to because of the following informalities:
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code in section 0087 on page 22 Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
37 CFR 1.821(c) states that amino acid sequence encompassed by the sequence rules should be disclosed in a sequence listing and 37 CFR 1.821(d) states that the corresponding sequences should be identified by sequence identifier. In the instant case, section 0078 page 18 recites a sequence encompassed by the sequence rules (i.e. MGEF…..). Although unclear, if GRG5RG4R and N4RN4RNR (section 0078 page 18) are such that G, R and N are used to represent amino acids then those sequences are also encompassed by the sequence rules (ST.25 based on the international filing date of 11/16/21).
This application contains sequence disclosures that are encompassed by the definitions for nucleotide and/or amino acid sequences set forth in 37 C.F.R. § 1.821(a)(1) and (a)(2). However, this application fails to comply with the requirements of 37 C.F.R. §§ 1.821-1.825 for the reason(s) set forth on the attached Notice To Comply With Requirements For Patent Applications Containing Nucleotide Sequence And/Or Amino Acid Sequence Disclosures. Applicant must comply with the requirements of the sequence rules (37 CFR 1.821 - 1.825). APPLICANT IS GIVEN THREE MONTHS FROM THE DATE OF THIS LETTER WITHIN WHICH TO COMPLY WITH THE SEQUENCE RULES, 37 C.F.R. §§ 1.821-1.825. Failure to comply with these requirements will result in ABANDONMENT of the application under 37 C.F.R. § 1.821(g). Extensions of time may be obtained by filing a petition accompanied by the extension fee under the provisions of 37 C.F.R. § 1.136. In no case may an applicant extend the period for response beyond the six month statutory period. Direct the response to the undersigned. Applicant is requested to return a copy of the attached Notice to Comply with the response.
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Appropriate correction is required.
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 1-4, 7-8, 11 and 15-18 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.
Claim 1 refers to ‘aqueous composition comprising overlapping polypeptide chains’ as well as ‘entangled polypeptide’. In this context, it is unclear how to determine overlapping polypeptide chains. The specification merely refers to concentrated solutions having overlap (section 0089 pages 22-23). Since aqueous solutions contain polypeptides in three-dimensions it is unclear how to determine if chains are overlapping. It is unclear if chains must be bonded together or if they only are required to be in close proximity. It is unclear what is excluded from the claim. With respect to entangled, page 2 section 006 of the specification refers to ‘chains in the network can cross each other, resulting in chain entanglement’. It is unclear how to determine if chains have crossed each other. Page 23 section 0090 of the specification refers to figure 2 and ‘free of chain entanglement’ and ‘without entanglement’. However, at least block 14 and block 18 of figure 2 appear to show chains that are touching or crossed. The bottom right corner of block 18 of figure 2 is as follows:
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. Such depiction appears to show one line that crosses another line. It is unclear why this is characterized as free of chain entanglement. It appears that the determination is subjective. None of the dependent claims clarify the claim scope.
Claim 17 refers to ‘NuG2’, ‘GB1’, ‘GA’, ‘GRG5RG4R’ and ‘N4RN4RNR’ which are merely described in the specification as ‘other polyproteins’ (page 18 section 0078). The sequences of these proteins is unclear. Although the specification defines certain terms (section 0063) and provides a sequence for FL (section 0078), the sequences of NuG2’, ‘GB1’, ‘GA’, ‘GRG5RG4R’ and ‘N4RN4RNR’ are unclear. It is unclear if each letter is an amino acid or representative of something else. If each letter represents an amino acid then ‘u’ and ‘B’ are unclear since those are not standard amino acid abbreviations.
Although unclear, the claims have been given the broadest reasonable interpretation consistent with the specification.
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 (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 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)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1-4, 7-8, 11 and 15-18 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Fu et al. (NPL citation 21 of IDS 11/26/23; ‘Fu’).
The first page of Fu states that is was posted May 20, 2021. The priority of the instant claims is addressed in the priority section above. Fu recites numerous authors who are not recited as inventors so it is not readily apparent that it is an inventor originated disclosure (MPEP 2153.01(a) 2nd paragraph).
Fu teach that FL is a designed ferredoxin-like globular protein (page 4 first paragraph). Fu teach that (FL)8 was prepared in PBS containing 7M GdHcl and that the denatured protein was crosslinked into hydrogels and renatured in PBS (pages 20-21 connecting paragraph). Fu teach the use of 200 mg/ml of the protein (page 21 first complete paragraph).
In relation to claim 1, Fu teach that (FL)8 was prepared in PBS containing 7M GdHcl and that the denatured protein was crosslinked into hydrogels and renatured in PBS (pages 20-21 connecting paragraph). Fu refers to overlap and entangling at concentrations above 150 mg/ml (page 4 2nd paragraph). Fu teach the use of 200 mg/ml of the protein (page 21 first complete paragraph). PBS would contain water and is an aqueous composition.
In relation to claims 2-4, Fu teach that (FL)8 was prepared in 7M GdHcl (pages 20-21 connecting paragraph).
In relation to claim 7, Fu teach the use of 200 mg/ml of the protein (page 21 first complete paragraph) which is 20% (w/v).
In relation to claim 8, Fu teach renaturing in PBS (pages 20-21 connecting paragraph).
In relation to claims 11 and 15-18, Fu teach that FL is a designed ferredoxin-like globular protein (page 4 first paragraph). Fu teach (FL)8 (pages 20-21 connecting paragraph).
Claim(s) 1 and 11 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Li et al. (‘Effect of preheating-induced denaturation during protein production on the structure and gelling properties of soybean proteins’ Food Hydrocolloids v105 2020 pages 1-10; ‘Li’).
The bottom of the first page of Li states that is was available online March 10 2020.
Li teach that a protein solution was prepared in distilled water (section 2.3 on page 2). Li teach to prepare protein gels that the solution was subjected to heating temperatures (section 2.9 on page 3). Li teach that the preheating induced denaturation (abstract and section 3.1). Li teach that cross-linking occurs between free sulfhydryl groups and shows in figure 4 a decrease in free sulfhydryl indicating the formation of disulphide bonds (section 3.3 and figure 4). Li teach improved gel hardness, elasticity and water-holding capacity (section 3.5.2). Li refers to globulin subunits of the protein (section 4).
In relation to the denaturing of claim 1, Li teach to prepare protein gels that the solution was subjected to heating temperatures (section 2.9 on page 3). Li teach that the preheating induced denaturation (abstract and section 3.1). Li teach that a protein solution (an aqueous composition) was prepared in distilled water (section 2.3 on page 2).
In relation to the crosslinking of claim 1, Li teach that cross-linking occurs between free sulfhydryl groups and shows in figure 4 a decrease in free sulfhydryl indicating the formation of disulphide bonds (section 3.3 and figure 4).
In relation to claim 11, Li refers to globulin subunits of the protein (section 4).
Although unclear (see 112 rejection above), the claim limitations have been interpreted as being met by Li.
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.
Claim(s) 1-4, 7-8, 11 and 15-18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Fang et al. (NPL cite 19 of IDS 11/26/23; ‘Fang’) in view of Li et al. (‘Effect of preheating-induced denaturation during protein production on the structure and gelling properties of soybean proteins’ Food Hydrocolloids v105 2020 pages 1-10; ‘Li’).
Fang teach the formation of hydrogels using a protein that has a ferredoxin-like fold structure (abstract). Fang specifically teach the FL domain as 82 residues (page 2 first paragraph of column 2). Fang teach an engineered tandem modular protein (FL)8 containing 8 FL domains (page 2 last paragraph). Fang teach photochemical cross-linking to allow cross-linking of tyrosines in close proximity (page 2 last paragraph). Fang teach the use of 200 mg/ml of the protein and PBS buffer (page 8 2nd to last paragraph). Fang teach that forced unfolding and aggregation in hydrogels is believed to be largely responsible for excellent mechanical properties (page 5 paragraph connecting columns 1-2). Fang teach that guanidine hydrochloride (GuHCl) was used to denature the protein and lead to significant swelling and aggregates (page 5 last complete paragraph and figure 6). Fang teach removal of GuHCl to renature the hydrogels which leads to increased Young’s modulus (figure 6 caption) which is believed to be due to formation of aggregation (page 6 first paragraph). Fang teach cross-linked, highly elastic protein hydrogels (abstract).
Fang does not teach denaturing followed by photochemical cross-linking.
Li teach the effects of denaturation on the structure and gelling properties of proteins (title and abstract). Li teach that denaturation allows functional groups to become available for intermolecular interactions and reactions can occur that play a key role in cross-linking and also lead to increased protein aggregation (page 1 paragraph connecting columns 1-2). Li teach improved gel hardness, elasticity and water-holding capacity (section 3.5.2 and figures 7 and 8). Li teach that denaturation improved the properties of the gels (section 4). Li teach that a protein solution was prepared in distilled water (section 2.3 on page 2).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the teachings of Fang because Fang teach cross-linking of tyrosine in close proximity (page 2 last paragraph). Since Li teach that denaturation allows functional groups to become available for intermolecular interactions and reactions can occur that play a key role in cross-linking and also lead to increased protein aggregation (page 1 paragraph connecting columns 1-2) one would have been motivated to denature to allow for the cross-linking and aggregation. Fang teach that guanidine hydrochloride (GuHCl) was used to denature the protein and lead to significant swelling and aggregates (page 5 last complete paragraph and figure 6). Fang teach removal of GuHCl to renature the hydrogels which leads to increased Young’s modulus (figure 6 caption) which is believed to be due to formation of aggregation (page 6 first paragraph). In the instant case, both of the references recognize denaturation and one would have been motivated to carry out the denaturing step before cross-linking because Li teach that denaturation allows functional groups to become available for intermolecular interactions and reactions can occur that play a key role in cross-linking and also leads to increased protein aggregation (page 1 paragraph connecting columns 1-2) and teach improved gel hardness, elasticity and water-holding capacity (section 3.5.2 and figures 7 and 8). In addition, MPEP 2144.04 IV C recognizes a selection of any order or mixing ingredients is prima facie obvious.
In relation to the denaturing of claim 1, Fang teach that guanidine hydrochloride (GuHCl) was used to denature the protein and lead to significant swelling and aggregates (page 5 last complete paragraph and figure 6). Li teach that denaturation allows functional groups to become available for intermolecular interactions and reactions can occur that play a key role in cross-linking and also lead to increased protein aggregation (page 1 paragraph connecting columns 1-2). Thus, one would have been motivated to carry out the denaturing prior to the crosslinking step. With respect to the aqueous composition, Fang teach the use of PBS buffer (page 8 2nd to last paragraph). Li teach that a protein solution (an aqueous composition) was prepared in distilled water (section 2.3 on page 2).
In relation to the crosslinking of claim 1, Fang teach photochemical cross-linking to allow cross-linking of tyrosines in close proximity (page 2 last paragraph).
In relation to claims 2-4, Fang teach that guanidine hydrochloride (GuHCl) was used to denature the protein and lead to significant swelling and aggregates (page 5 last complete paragraph and figure 6).
In relation to claim 7, Fang teach the use of 200 mg/ml of the protein (page 8 2nd to last paragraph) which is 20% (w/v).
In relation to claim 8, Fang teach removal of GuHCl to renature the hydrogels which leads to increased Young’s modulus (figure 6 caption)
In relation to claims 11 and 15-18, Fang teach the formation of hydrogels using a protein that has a ferredoxin-like fold structure (abstract). Fang specifically teach the FL domain as 82 residues (page 2 first paragraph of column 2). Fang teach an engineered tandem modular protein (FL)8 containing 8 FL domains (page 2 last paragraph).
Although unclear (see 112 rejection above), the claim limitations have been interpreted as being met by the combination of the references
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-4, 7-8, 11 and 15-18 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-39 of copending Application No. 19/167,042 (reference application; ‘042’). Although the claims at issue are not identical, they are not patentably distinct from each other.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
042 recites methods of preparing a protein hydrogel comprising denaturing, crosslinking and optionally renaturing (claim 15). 042 recites subjecting the protein to guanidium chloride (claim 27). 042 recites a concentration of the protein of about 20 % (w/v) (claim 28). 042 teach renaturing (claim 29). 042 teach that the protein comprises ferredoxin-like folds (claim 20) and specifically recites SEQ ID NO:10 (claim 25) (where the sequence is set forth on page 28 of the specification).
In relation to claim 1, 042 recites methods of preparing a protein hydrogel comprising denaturing, crosslinking and optionally renaturing (claim 15).
In relation to claims 2-4, 042 recites subjecting the protein to guanidium chloride (claim 27).
In relation to claim 7, 042 recites a concentration of the protein of about 20 % (w/v) (claim 28).
In relation to claim 8, 042 teach renaturing (claim 29).
In relation to claims 11 and 15-18, 042 teach that the protein comprises ferredoxin-like folds (claim 20) and specifically recites SEQ ID NO:10 (claim 25) (where the sequence is set forth on page 28 of the specification) where SEQ ID NO:10 comprises 8 FL repeats.
Conclusion
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RONALD T. NIEBAUER
Primary Examiner
Art Unit 1658
/RONALD T NIEBAUER/Examiner, Art Unit 1658