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 .
Priority
The instant application claims priority to U.S. Provisional Applications 63/079,187, 63/093,554, and 63/149,068 filed on 09/16/2020, 10/19/2020, and 02/12/2021, respectively. U.S. PRO 63/079,187 finds support for the instantly claimed invention, Claims 1 and 41; therefore, the effective filing date of these claims is 09/16/2020.
The remaining elected claims, 27-30 and 32-39 are not given this priority date, as none of the limitations of “thermal reactive group,” sulfo-NHS, Photo-reactive group, or aryl ketones/benzophenones are anywhere in the claims by way of explicit or implicit support. As such, the priority date for the limitations of claims 27-30 and 32-39 is 09/19/21.
Election/Restrictions
Applicant’s election without traverse of Group I, claims 26-41, and the species, in the reply filed on 08/10//2026 is acknowledged. Claims 1-25 and 31 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention or species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 08/10/26.
Claims 26-30 and 32-41 are under examination because although claim 29 is not drawn to the elected species, art was found that reads on this claim. An Office action on the merits follows.
Claim Rejections - 35 USC § 112(B)
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.
Claims 26-30 and 32-41 are rejected under 35 U.S.C. 112(b) 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 26 recites “amplified desired characteristic,” which is relative terminology because it is unclear how the “amplified” characteristic is objectively measured, or which characteristic is being considered, as there is nothing in the claims that is drawn to any particular property with any quantifiable standard by which “amplified” can be measured. Additionally, "desired" is subjective, which is also relative terminology, rendering it indefinite. The instant specification does not provide example(s), teaching(s), or definition(s) on how to measure a desired characteristic and what is considered “amplified.”
As such, the instant specification lacks a standard for measuring the degree intended and one of ordinary skill in the art would not readily understand how to determine whether or not a characteristic is amplified (MPEP 2173.05(n)).
Claims 26-41 recite methods of deriving peptides containing desired characteristics; however, it is unclear how the added peptides exhibiting desired characteristics in claim 26 are differentiated from the peptides exhibiting desired characteristics derived from the collagen in claims 27-41; meaning, it is not clear if these peptides have the same desired characteristics, or different desired characteristics from the original “collagen product,” vs. the “collagen” and the “modified collagen.” The lack of clarity in the claims as to the method of adding peptides, and how the reaction differentiates the final targeted collagen product with regard to structure, and physical properties is required.
Claim 26 (with dependent claims 27-41) recite “desired characteristic.” This is relative terminology because the term “desired” is not defined by the claim, and the specification does not provide a limiting definition of what would be considered desirable, as it can vary between skill artisans, their intended purpose and/or use for the collagen, what types of materials are used in the method, etc. None of these are provided with clarity for the term “desired.”
Therefore, one of ordinary skill in the art is not able to ascertain the metes and bounds of what desired characteristic(s) exhibited by the collagen product and/or the peptides is intended to be included in, or excluded from, the collagen, the peptide, the modified collagen and the targeted collagen product.
For purposes of examination the claimed “peptide(s)” will be any peptide added to collagen that forms a bond with any functional group on the collagen.
Claim 37 recites the limitation "reagent" There is insufficient antecedent basis for this limitation in the claim, rendering it unclear how the reagent is incorporated into the collogen target product.
Claim 28 recites the phrase "e.g.," or “for example,” which renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim Rejections - 35 USC § 112(A)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
Claims 26-30 and 32-41 are rejected under 35 U.S.C. 112(a) as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 26-41 are drawn to a collagen product modified with “peptides exhibiting a desired characteristic”; however, claiming peptides that have a “desired characteristic” is unclear, as discussed above, and is not supported in the instant specification because it does not describe these peptides in enough specificity to show possession of the entire genus of the instant claims.
MPEP § 2137 states that "the written description requirement for a genus must be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus (see i)(C), above). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
For written description, the analysis (a) considers actual reduction to practice, (b) disclosure of drawing or structural chemical formulas, (c) sufficient relevant identifying characteristics in the way of complete/partial structure or physical and/or chemical properties, functional characteristics when coupled with known or disclosed and (d) representative number of examples.
(a) actual reduction to practice/(b) disclosure of drawing or structural chemical formulas:
The instant specification states “Different peptides have different biological properties that imbue them with desired/desirable attributes/characteristics, such as a higher affinity for therapeutic usage in specific medical applications” [00180. The instant specification also states, “In various embodiments, the collagen fractions or synthesized collagen peptide (e.g., CHP or CMP) can be a single-, double- or triple-stranded peptide” (see, e.g., instant specification, [00184]). Furthermore, the specification states “In an embodiment, after digestion and fragmentation of the collagen tissue, each of the collagen fractions/peptides is tested (130) for various biological properties, such as, for example, attributes/characteristics that are useful for wound healing, blood clotting, bone formation/osteogenesis, cosmetic application, scaffolds for organ regeneration, use as antioxidants, antibacterial and/or anti-inflammatory activity, and for the delivery of drugs such as insulin and methylene blue, showing lower water absorbency” [00180]. Additionally, the instant specification states that “it is recognized that more than a single desired characteristic may be engineered into or out of the targeted collagen [00180].
(c) sufficient relevant identifying characteristics in the way of complete/partial structure or physical and/or chemical properties
The instant claims do not require any structural attributes or provide any guidance as to the type of modifications to collagen, the required structure of functional groups, required reaction environment, or any measurable way to ascertain the change of function, what is desirable or how the peptide are added. In sum, there are no relevant characteristics supported in the claims by way of any identifying structure or function in the current claims.
(d) Representative number of examples
A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure "indicates that the patentee has invented species sufficient to constitute the gen[us]." See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004)("[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated.").
The instant application does not have any relevant data that can be used to support the instant claims. The examples of the specification are hypothetical, meaning that they are supported by what is known in the art, rather than what was done to differentiate the claimed method and present a final collagen product with specific or quantifiable modifications to its structure or function. Given this lack of description in the specification, the application fails to describe the claimed invention in such a full, clear, and concise and exact terms that a skilled artisan would recognize that applicants were in possession of the genus of claimed invention.
Claim Rejections - 35 USC § 102(A)(1)
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.
Claims 26-29, 38, 39 and 41 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Usha et al. (Colloids and Surfaces B: Biointerfaces. 90 (2012) 83– 90).
Usha teaches the effect of adding l-lysine on the conformational, rheological, and thermal properties of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and N-hydroxysuccinimide (NHS) cross linked collagen on the self-assembly processes for collagen modification (Abstract). This study finds that in the absence of adding l-lysine, the rheological characterization of collagen cross linked with EDC/NHS showed an increase in shearing stress with shearing speed, which indicates that the collagen chains become rigid, and the molecules are reluctant to flow (abstract). Usha teaches that this addition of lysine peptides the incorporation of l-lysine in the EDC/NHS cross linking favors the molecular stability of collagen (abstract; section 2.2, p. 84). This reference concludes that the collagen is stabilized by adding l-lysine to incorporate it into the EDC/NHS crosslinking, which favors the molecular and phase structure and self-assembly process (abstract, p. 89). This reference teaches that the presence of l-lysine creates an increased proximity of collagen molecules exposing sufficient reactive groups, which provides for more for more crosslinks to stabilize the collagen (p. 89, Col. 2).
Usha meets the limitations of claim 26 by teaching each of the required method steps: 1) adding peptides (l-lysine) to the collagen. The adding step is the only active step in the claimed method, and no clear peptide, type of modified collagen, active crosslinking steps, measurable characteristics, etc. are included in claim 26. As such, adding lysine to collagen and forming a modified collagen product meets these limitations. Furthermore, the inherent limitation of “where the crosslinking occurs…” is met because this reference also teaches the same thermal reactive crosslinkers as claimed (NHS/EDC), meeting the limitations of claims 27-29. Claims 38 and 39 are met because l-lysine is added to collagen, and lysine is the “end-cap” to the collagen or to the “peptide,” as both the peptide and the collagen are modified when peptides are added, as well as when crosslinking occurs. As to claim 41, this reference teaches that the collagen is reconstituted after EDC/NHS in the presence and absence of lysine (p. 84-85, section 2.6.3).
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.
Claim(s) 26-30 and 32-41 are rejected under 35 U.S.C. 103 as being unpatentable over Usha, as applied to claims 26-29, 38, 39 and 41 above, inv view of Belsom et al. (Anal. Chem. 2017, 89, 5319−532).
The teachings of Usha have been described supra.
The difference between the prior art and the instant claims is that Usha does not teach the thermal-reactive groups or the photoreactive groups of the instant claims.
Belsom teaches that the use of a heterobifunctional photoactivatable cross linker with sulfo-SDA (diazirine), has yielded high-density data that facilitated structure modeling of individual proteins, which can be modified by a photoactivatable second reagent, sulfo-SBP. i.e., benzophenone (abstract). This reference further teaches that N-hydroxysuccinimide (NHS) ester cross-linkers are predominantly used in crosslinking/ mass spec. analysis, which limits the level of protein structure detail available in the art, but has provided motivation to modify the crosslinking regents in processes, such as photo-cross linking, which have often failed to demonstrate significant increases in available data (abstract). This reference concludes that photo-cross-linking is a means to increase the density of cross-linking/mass spectrometry data, which allows interrogation of protein structures in complex environments and leads to additional structural insights by accessing protein regions that are inaccessible with one cross-linker alone (p. 5323, Col. 1).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to have taken the method of Usha and used the sulfo-NHS/EDC/benzophenone derivative crosslinking pairs as the modifier, because Belsom teaches that these thermal/photo-reactive pairs are effective crosslinking groups for similar peptide matrices (e.g., albumin). One would have been motivated to do so because Belsom teaches the crosslinking groups used in the same method for the same purpose of creating a crosslinked product with the collagen of Usha, as a template for crosslinking with NHS/photo-reactive groups, as taught for HSAQ in Belsom. As such, the sulfo-NHS and benzophenone combination has a reasonable expectation of success to be effective in the method of Usha.
Therefore, claim 30 is met by Belsom teaching sulfo-NHS. Claims 32-27 are met because benzophenones are added in multiples, so one of ordinary skill in the art would recognize that the reactions of photo-reactive groups will inherently (see MPEP 2112.01) occur when the prior art method steps are taken. Claims 32-29 are met because benzophenones are aryl ketones, added with NHS as a photo-reactive group. Claim 40 is met because , the term “standard peptide synthesizer,” is not defined in the specification. As such, any environment that a “synthesizer” is present, regardless of the lack of definition for “synthesizer,” will meet the limitations of this claim (see lysine synthesis, p. 5319-5320, Col. 2- Col. 1).
As such, claims 26-30 and 32-41 are met.
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.
Claim 26 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 18/025,782 (reference application; herein referred to as “App’782”). Although the claims at issue are not identical, they are not patentably distinct from each other because claim 26 teaches the same method of adding peptides to collagen to modify a characteristic.
Claims 26-41 are rendered obvious by ‘782, as applied to claim 1 above, in view of Belsom et al. (Anal. Chem. 2017, 89, 5319−532).
As discussed above, one would have been motivated at the effective filing date of the invention to have taken the method of ‘782 and used the sulfo-NHS/EDC/benzophenone derivative crosslinking pairs as the modifier, because Belsom teaches that these thermal/photo-reactive pairs are effective crosslinking groups. One would have been motivated to do so because Belsom teaches the crosslinking groups used in the same method for the same purpose of creating a crosslinked product with the collagen of ‘782, as a template for crosslinking with NHS/photo-reactive groups, as taught in Belsom. As such, the sulfo-NHS and benzophenone combination has a reasonable expectation of success to be effective in the method of ‘782.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEANETTE M LIEB whose telephone number is (571)270-3490. The examiner can normally be reached M-F 10-7.
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/JEANETTE M LIEB/Primary Examiner, Art Unit 1654
