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 .
Applicants’ amendment to the claims filed on 2/8/2024 is acknowledged. This listing of claims replaces all prior listings of claims in the application.
Claims 1-13, 15-16 are pending.
Claim 14 is canceled.
Election/Restrictions
Applicant’s election with traverse of Group I (claims 1-11, 15-16) in the reply filed on 5/28/2026 is acknowledged. Applicant contends that Examiner has not provided a specific sequence alignment, percent identity calculation or other supporting technical evidence to substantiate that there is a shared technical feature between a polynucleotide encoding an amino acid sequence that is at least 60% identical to the amino acid sequence of SEQ ID NO:1 and the process of making said construct. Examiner contends that Yoshizumi teaches a bacterial collagen-like protein from Streptococcus pyogenes of which contains the collagen triple-helical domain of sequence (Gly-Xaa-Yaa)79 (CL) (abstract). The CL domains were obtained from the intact proteins (page 1243, column 1, para 2). The construct of the instant application can be as small as 27 amino acids as a collagen-like protein fails to form its characteristic triple-helix structure the moment the strict Gly-X-Y repeating sequence is broken or when the chain falls below a minimum length of about 9 continuous triplets (27 amino acids) Gly-X-Y repeating motif. As such, Examiner maintains the position that the CL domains taught by Yoshizumi would have at least 60% sequence identity to SEQ ID NO: 1 with at least 38 amino acids deleted from the N-terminus as Yoshizumi teaches a bacterial collagen-like protein from Streptococcus pyogenes of which contains the collagen triple-helical domain of sequence (Gly-Xaa-Yaa)79 (CL) (abstract). Therefore, this argument is found to be not persuasive. Applicant is reminded that the evidence of burden of search does not apply to examination of PCT applications upon entering the national stage. MPEP § 1893.03(d) states "the principles of unity of invention are used to determine the types of claimed subject matter and the combinations of claims to different categories of invention that are permitted to be included in a single international or national stage patent application." See MPEP § 1850 for a detailed discussion of Unity of Invention. The basic principle is that an application should relate to only one invention or, if there is more than one invention, that applicant would have a right to include in a single application only those inventions which are so linked as to form a single general inventive concept." A group of inventions is considered linked to form a single general inventive concept where there is a technical relationship among the inventions that involves at least one common or corresponding special technical feature. The expression special technical feature is defined as meaning those technical features that define the contribution which each claimed invention, considered as a whole, makes over the prior art.
Claims 1-11, 15-16 are pending and examined on the merits.
Claims 12-13 are withdrawn from further consideration pursuant to 37 CFR 1.142(b).
Claim 14 is cancelled.
Priority
Acknowledgement is made of this national stage entry of PCT/EP2022/071834 filed on 8/3/2022, which claims domestic priority to U.S. non-provisional application 18/682,348, filed on 8/3/2022, which claims foreign priority under 35 U.S.C. 119(a)-(d) to European Patent Application No. EP21190325.7, filing date 8/9/2021. The certified copy has been filed in the present application on 2/8/2024.
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Information Disclosure Statement
The information disclosure statement (IDS) submitted on 2/8/2024, 4/2/2024, 4/19/2024, 4/3/2026 is acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
Drawings
The Drawings filed on 3/4/2024 are acknowledged and accepted by the Examiner.
Objection to the Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. 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. The hyperlink can be found on page 2, lines 6 of the specification.
Claim Rejections - 35 USC § 112
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.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
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 of carrying out his invention.
Claims 1-11, 15-16 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, 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.
MPEP 2163.II.A.2.(a).i) states, “Whether the specification shows that applicant was in possession of the claimed invention is not a single, simple determination, but rather is a factual determination reached by considering a number of factors. Factors to be considered in determining whether there is sufficient evidence of possession include the level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention”.
For claims drawn to a genus, MPEP § 2163 states the written description requirement for a claimed genus may 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 Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
Claims 1-11, 15-16 are drawn to a polynucleotide encoding an amino acid sequence that is at least 60% identical to the amino acid sequence of SEQ ID NO:1, wherein the polynucleotide is a replicable polynucleotide encoding a collagen-like protein, and wherein the amino acid sequence comprises a deletion of at least 38 amino acids at the N-terminus of the amino acid sequence of SEQ ID NO: 1. The structure of a polynucleotide encoding an amino acid sequence with an N-terminus deletion of at least 38 amino acids having at least 60% identity to SEQ ID NO: 1 is a large number of sequences as the amino acid sequence of the remaining 40% is unknown. The construct of the instant application can be as small as 27 amino acids as a collagen-like protein fails to form its characteristic triple-helix structure the moment the strict Gly-X-Y repeating sequence is broken or when the chain falls below a minimum length of about 9 continuous triplets (27 amino acids) Gly-X-Y repeating motif. As such, the structure of a polynucleotide encoding an amino acid sequence that is at least 60% identical to the amino acid sequence of SEQ ID NO:1, wherein the amino acid sequence comprises a deletion of at least 38 amino acids at the N-terminus of the amino acid sequence of SEQ ID NO: 1 is a large number of sequences.
Claims 3 is drawn to the polynucleotide according to claim 1, encoding an amino acid sequence that is at least 60% identical to the amino acid sequence of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8 or SEQ ID NO:9. The structure of a polynucleotide encoding an amino acid sequence with an N-terminus deletion of at least 38 amino acids having at least 60% identity to SEQ ID NO: 1 and at least 60% sequence identity to NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8 or SEQ ID NO:9. are a large number of sequences as the amino acid sequence of the remaining 40% of SEQ ID NO: 2 is unknown. The construct of the instant application can be as small as 27 amino acids as a collagen-like protein fails to form its characteristic triple-helix structure the moment the strict Gly-X-Y repeating sequence is broken or when the chain falls below a minimum length of about 9 continuous triplets (27 amino acids) Gly-X-Y repeating motif. As such, the structure of a polynucleotide encoding an amino acid sequence that is at least 60% identical to the amino acid sequence of SEQ ID NO:1, wherein the amino acid sequence comprises a deletion of at least 38 amino acids at the N-terminus of the amino acid sequence of SEQ ID NO: 1 and at least 60% sequence identity to SEQ ID NO: 2 is a large number of sequences.
In this case, the specification discloses the following representative species of a collagen-like protein as encompassed by the claims (i.e. SEQ ID NO: 1 with an N-terminal deletion of 38-90 amino acids). Other than the above disclosed species, there is no prior-art or disclosed teaching as to the large number of collagen-like protein that would encompass at least 40% variability. The breadth of the claims encompass a large number of sequences of collagen-like proteins with 40% variability.
An adequate written description of a chemical invention also requires a precise definition, such as by structure, formula, chemical name, or physical properties, and not merely a wish or plan for obtaining the chemical invention claimed. See, e.g., Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 927, 69 USPQ2d 1886, 1894-95 (Fed. Cir. 2004). Here, the disclosure fails to teach which combinations of amino acids out of the numerous possibilities encompass the 40% variability for the production of collagen-like protein.
Scope of Enablement
Claims 1-11, 15-16 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a polynucleotide encoding an amino acid sequence with 100% sequence identity to SEQ ID NO: 1 and a N-terminal deletion of 38-90 amino acids, it does not reasonably provide enablement for all collagen-like protein having 40% variation with a deletion of at least 38 amino acids as said construct is comprised of a large number of sequences as encompassed by the claims. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
The test of enablement is not whether any experimentation is necessary, but whether, if experimentation is necessary, it is undue.” In re Angstadt, 537 F.2d 498, 504, 190 USPQ 214, 219 (CCPA 1976). Factors to be considered in determining whether undue experimentation is required are summarized in In re Wands (858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)) as follows: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. See MPEP § 2164.01(a). The Factors considered to be most relevant to the instant rejection are addressed in detail below.
(A)The breadth of the claims:
Claims 1-11, 15-16 are drawn to a polynucleotide encoding an amino acid sequence that is at least 60% identical to the amino acid sequence of SEQ ID NO:1, wherein the polynucleotide is a replicable polynucleotide encoding a collagen-like protein, and wherein the amino acid sequence comprises a deletion of at least 38 amino acids at the N-terminus of the amino acid sequence of SEQ ID NO: 1. The structure of a polynucleotide encoding an amino acid sequence with an N-terminus deletion of at least 38 amino acids having at least 60% identity to SEQ ID NO: 1 is a large number of sequences as the amino acid sequence of the remaining 40% is unknown. The construct of the instant application can be as small as 27 amino acids as a collagen-like protein fails to form its characteristic triple-helix structure the moment the strict Gly-X-Y repeating sequence is broken or when the chain falls below a minimum length of about 9 continuous triplets (27 amino acids) Gly-X-Y repeating motif. As such, the structure of a polynucleotide encoding an amino acid sequence that is at least 60% identical to the amino acid sequence of SEQ ID NO:1, wherein the amino acid sequence comprises a deletion of at least 38 amino acids at the N-terminus of the amino acid sequence of SEQ ID NO: 1 is a large number of sequences.
Claims 3 is drawn to the polynucleotide according to claim 1, encoding an amino acid sequence that is at least 60% identical to the amino acid sequence of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8 or SEQ ID NO:9. The structure of a polynucleotide encoding an amino acid sequence with an N-terminus deletion of at least 38 amino acids having at least 60% identity to SEQ ID NO: 1 and at least 60% sequence identity to NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8 or SEQ ID NO:9. are a large number of sequences as the amino acid sequence of the remaining 40% of SEQ ID NO: 2 is unknown. The construct of the instant application can be as small as 27 amino acids as a collagen-like protein fails to form its characteristic triple-helix structure the moment the strict Gly-X-Y repeating sequence is broken or when the chain falls below a minimum length of about 9 continuous triplets (27 amino acids) Gly-X-Y repeating motif. As such, the structure of a polynucleotide encoding an amino acid sequence that is at least 60% identical to the amino acid sequence of SEQ ID NO:1, wherein the amino acid sequence comprises a deletion of at least 38 amino acids at the N-terminus of the amino acid sequence of SEQ ID NO: 1 and at least 60% sequence identity to SEQ ID NO: 2 is a large number of sequences.
B) The nature of the invention; C) The state of the prior art; (D) The level of one of ordinary skill; and (E) The level of predictability in the art: As noted above, the scope of the claimed 40% variability is a large number of sequences.
It is well-known in the prior art that the amino acid sequence of a polypeptide determines the polypeptide’s functional properties. The positions within a protein's sequence where modifications can be made with a reasonable expectation of success in obtaining a polypeptide having the desired activity/utility are limited in any protein and the result of such modifications is highly unpredictable. In addition, one skilled in the art would expect any tolerance to modification for a given protein to diminish with each further and additional modification, e.g., multiple substitutions. The reference of Singh et al. (Current Protein and Peptide Science, 2017; examiner cited) reviews various protein engineering methods and discloses that despite the availability of an ever-growing database of protein structures and highly sophisticated computational algorithms, protein engineering is still limited by the incomplete understanding of protein functions, folding, flexibility, and conformational changes [see p. 7, column 1, top]. The reference of Zhang et al. (Structure, 2018; examiner cited) discloses that a mutation of a residue that was predicted to be benign caused significant structural changes and unexpected effects on the function of a polypeptide [p. 1475, column 1].
It is well-known in the art that even a single amino acid alteration can alter the folding of a polypeptide. See, e.g., MPEP 2144.08.II.A.4.(c), which states, “[i]n the area of biotechnology, an exemplified species may differ from a claimed species by a conservative substitution (“the replacement in a protein of one amino acid by another, chemically similar, amino acid... [which] is generally expected to lead to either no change or only a small change in the properties of the protein.” Dictionary of Biochemistry and Molecular Biology 97 (John Wiley & Sons, 2d ed. 1989)). The effect of a conservative substitution on protein function depends on the nature of the substitution and its location in the chain. Although at some locations a conservative substitution may be benign, in some proteins only one amino acid is allowed at a given position. For example, the gain or loss of even one methyl group can destabilize the structure if close packing is required in the interior of domains. James Darnell et al., Molecular Cell Biology 51 (2d ed. 1990).”
(F) The amount of direction provided by the inventor and (G) The existence of working examples: The specification discloses the following working examples of a collagen-like protein (i.e. SEQ ID NO: 1 with an N-terminal deletion of 38-90 amino acids). Other than the above disclosed species, there is no prior-art or disclosed teaching as to the number of sequences that comprises the 40% variability of collagen-like protein. Other than the above disclosed species, there is no prior-art or disclosed teaching as to the large number of sequences that comprise the 40% variability of the claimed collagen-like protein.
In view of the overly broad scope of the claims, the lack of guidance and working examples provided in the specification, the high level of unpredictability, and the state of the prior art, undue experimentation would be necessary for a skilled artisan to make and use the entire scope of the claimed invention. Applicants have not provided sufficient guidance to enable one of ordinary skill in the art to make and use the claimed invention in a manner reasonably correlated with the scope of the claims. The scope of the claims must bear a reasonable correlation with the scope of enablement (In re Fisher, 166 USPQ 19 24 (CCPA 1970)). Without sufficient guidance, determination of having the desired biological characteristics is unpredictable and the experimentation left to those skilled in the art is unnecessarily, and improperly, extensive and undue. See In re Wands 858 F.2d 731, 8 USPQ2nd 1400 (Fed. Cir, 1988).
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.
Claims 1-11, 15-16 are rejected under 35 U.S.C. 102a1 as being unpatentable over Miroshnychenko et al (WO 2010091251 A2, Date of Publication: 12 August 2010, cited on IDS dated 2/8/2024) {herein Miroshnychenko}.
Claims 1-11, 15-16 are drawn to a polynucleotide encoding an amino acid sequence that is at least 60% identical to the amino acid sequence of SEQ ID NO:1, wherein the polynucleotide is a replicable polynucleotide encoding a collagen-like protein, and wherein the amino acid sequence comprises a deletion of at least 38 amino acids at the N-terminus of the amino acid sequence of SEQ ID
NO: 1.
With respect to claims 1-11, 15-16, Miroshnychenko teaches a collagen-like protein that is at least 60% identical to the instant application SEQ ID NO: 1 from Streptococcus pyogenes (appendix A; para 0010, 0012, 00137). Said sequence is lacking 90 amino acids from the N-terminus of the instant application SEQ ID NO: 1 (appendix A). As such, it is the Examiner’s position that the recitation ‘wherein the amino acid sequence comprises a deletion of between 38-90 amino acids at the N-terminus of the amino acid sequence of SEQ ID NO: 1’ is taught since the amino acid sequence comprises a deletion of 90 amino acids at the N-terminus of the amino acid sequence of SEQ ID NO: 1. Furthermore, said sequence is 100% identical to the instant application SEQ ID NO: 2 as it is comprised of the amino acid sequence of SEQ ID NO: 1 with an amino acid deletion of 90 amino acids from the N-terminus (appendix B), as recited in the instant application claim 15. In one non-limiting example, two or more triple helical domains are inserted within a vector (para 0019). The expression construct may be cloned into E. coli competent cells (para 0053). Post-transformation, cells may be initially grown on suitable culture media (e.g. M9-casamino acid) at 37C (para 0053). Since the constructs are ‘grown’ on suitable culture media, it is the Examiner’s position that the nucleotide sequence of claim 1 is replicable. s. Miroshnychenko further teaches the construct is sub-cloned into the E. coli expression vector system and expressed in E. coli host cells (para 0053) or which is recited in the instant application claim 10. The E. coli expression vector system is fundamentally designed as an overexpression system since it uses strong, inducible promoters to force the bacteria to produce massive quantities of a specific recombinant protein. As such, it is the Examiner’s position that the polynucleotide is present in overexpressed form. Since Miroshnychenko teaches a polynucleotide encoding an amino acid sequence that is at least 60% identical to the instant application amino acid sequence SEQ ID NO: 1 and comprises a deletion of 90 amino acids at the N-terminus, it is the Examiner’s position that said construct would necessarily have the capability of secreting a bacterial collagen-like protein, as recited in the instant application claim 11. A yeast host cell may be selected from Pichia pastori (para 0054), as recited in the instant application claim 16(Claim #--???).
For the reasons stated herein, the teachings of Miroshnychenko anticipates claims 1-11, 15-16.
Conclusion
Status of claims
Claims 12-13 are withdrawn from further consideration pursuant to 37 CFR 1.142(b).
Claims 1-11, 15-16 are pending and examined on the merits.
Claim 14 is cancelled.
Claims 1-11, 15-16 are rejected.
No claims are in condition for allowance.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERICA NICOLE JONES-FOSTER whose telephone number is (571)270-0360. The examiner can normally be reached mf 7:30a - 4:30p.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Manjunath Rao can be reached at 571-272-0939. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ERICA NICOLE JONES-FOSTER/Examiner, Art Unit 1656
/MANJUNATH N RAO/Supervisory Patent Examiner, Art Unit 1656
Appendix A
Mirochnitchenko et al SEQ ID NO: 7 vs Instant Application SEQ ID NO: 1
Query Match 73.4%; Score 1338; Length 240;
Best Local Similarity 100.0%;
Matches 240; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 91 GSPGLPGPRGEQGPTGPTGPAGPRGLQGLQGLQGERGEQGPTGPAGPRGLQGERGEQGPT 150
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 GSPGLPGPRGEQGPTGPTGPAGPRGLQGLQGLQGERGEQGPTGPAGPRGLQGERGEQGPT 60
Qy 151 GLAGKAGEAGAKGETGPAGPQGPRGEQGPQGLPGKDGEAGAQGPAGPMGPAGERGEKGEP 210
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 GLAGKAGEAGAKGETGPAGPQGPRGEQGPQGLPGKDGEAGAQGPAGPMGPAGERGEKGEP 120
Qy 211 GTQGAKGDRGETGPVGPRGERGEAGPAGKDGERGPVGPAGKDGQNGQDGLPGKDGKDGQN 270
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 GTQGAKGDRGETGPVGPRGERGEAGPAGKDGERGPVGPAGKDGQNGQDGLPGKDGKDGQN 180
Qy 271 GKDGLPGKDGKDGQNGKDGLPGKDGKDGQDGKDGLPGKDGKDGLPGKDGKDGQPGKPGKY 330
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 GKDGLPGKDGKDGQNGKDGLPGKDGKDGQDGKDGLPGKDGKDGLPGKDGKDGQPGKPGKY 240
Appendix B
Mirochnitchenko et al SEQ ID NO: 7 vs Instant Application SEQ ID NO: 2
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Prosecution Insights