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 .
Claims 1-10, 12-15, 17, 19-22 and 24 are still at issue and are present for examination.
Election/Restrictions
Applicant's election with traverse of the invention of Group 1, claims 1-10, and 17 to a peptide or variant thereof, in the paper of 9/2/2026, is acknowledged. Applicant's election without traverse of the following species:
Species Group 1: SEQ ID NO:3.
Species Group 2: SEQ ID NO:8.
Species Group 3: SEQ ID NO:5.
Species Group 4: MELAS
Species Group 5: mt-tRNALeu(UUR)
Species Group 6: m.3243A>G in the MT-TP1 human gene encoding mt-tRNALeu(UUR),
in the paper of 9/2/2026, is acknowledged.
Applicants traverse the restriction requirement on the basis that applicants submit that Perli et al. does not disclose "a peptide having the amino acid sequence SEQ ID NO 1 and/or a fragment thereof of at least 8 amino acids of length, or variants of said peptide or fragment, wherein said peptide entirely consists of d-amino acids.". Applicants complete traversal and amendent of the claims are acknowledged and has been carefully considered, however, is not found persuasive for the reasons previously made of record and for those reasons repeated herein.
It is noted that applicants have amended the claims and while Perli et al. may no longer break unity of invention, Heavner et al. (US Patent No. 5,753,628) disclose an 8 amnio acid peptide wherein each of the 8 amino acids are D amino acids (see anticipation rejection below). Thus unity of invention is lacking.
Claims 10, 12-15, 19-22 and 24 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609 A(1) states, "the list may not be incorporated into the specification but must be submitted in a separate paper."
Applicants filing of information disclosure statements on 6/28/2024 and 9/2/2026 are acknowledged and have been considered.
Specification
The disclosure is objected to because of the following informalities:
Applicants specification is objected to because applicants specification comprises Nucleotide and/or Amino Acids Disclosures Requiring a "Sequence Identifier".
Applicants attention is directed to 37 CFR 1.821(a) which presents a definition for "nucleotide and/or amino acid sequences." This definition sets forth limits, in terms of numbers of amino acids and/or numbers of nucleotides, at or above which compliance with the sequence rules is required. Nucleotide and/or amino acid sequences as used in 37 CFR 1.821 through 37 CFR 1.825 are interpreted to mean an unbranched sequence of four or more amino acids or an unbranched sequence of ten or more nucleotides.
Specifically applicants specification at page 14 and page 15 recites “FRFK” which requires a sequence identifier each time it is listed. While it is recognized that FRFK corresponds with SEQ ID NO:8, it is listed at additional places in the specification without the required sequence identifier.as per 37 CFR 1.821 through 37 CFR 1.825.
Appropriate correction is required.
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.
Claim(s) 1-9 and 17 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim(s) 1-9 and 17 are directed to all possible peptides comprising at least 8 contiguous amino acids of SEQ ID NO 1 or a variant of SEQ ID NO 1, wherein said peptide entirely consists of d-amino acids; optionally further conjugated at the N-terminus with a mitochondrial (mt)-targeting sequence. The specification, however, only provides the representative species of that peptide comprising the amino acid sequence of SEQ ID NO: 1, encompassed by these claims. There is no disclosure of any particular structure to function/activity relationship in the disclosed species. The specification also fails to describe additional representative species of these encompassed peptides by any identifying structural characteristics or properties, for which no predictability of structure is apparent.
Regarding the level of skill and knowledge in the art of amino acid mutation and functionality, the reference of Singh et al. (Curr. Protein Pept. Sci. 18:1-11, 2017; cited on the attached Form PTO-892) 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). Also, the unpredictability associated with amino acid mutations is exemplified by the reference of Zhang et al. (Structure 26:1474-1485, 2018; cited on the attached Form PTO-892), which discloses that even a mutation of a surface residue that was predicted to be benign caused significant structural changes and unexpected effects on the function of a polypeptide (p. 1475, column 1).
Given this lack of additional representative species as encompassed by the claims, Applicants have failed to sufficiently describe the claimed invention, in such full, clear, concise, and exact terms that a skilled artisan would recognize Applicants were in possession of the claimed invention.
Applicant is referred to the revised guidelines concerning compliance with the written description requirement of U.S.C. 112, first paragraph, published in the Official Gazette and also available at www.uspto.gov.
Claim(s) 1-9 and 17 are rejected under 35 U.S.C. 112, first paragraph, because the specification, while being enabling for that peptides comprising at least 8 contiguous amino acids of SEQ ID NO 1, wherein said peptide entirely consists of d-amino acids, does not reasonably provide enablement for all possible peptides comprising at least 8 contiguous amino acids of SEQ ID NO 1 or a variant of SEQ ID NO 1, wherein said peptide entirely consists of d-amino acids; optionally further conjugated at the N-terminus with a mitochondrial (mt)-targeting sequence. 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 use the invention commensurate in scope with these claims.
Factors to be considered in determining whether undue experimentation is required, are summarized in In re Wands (858 F.2d 731, 8 USPQ 2nd 1400 (Fed. Cir. 1988)) as follows: (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claim(s).
Claim(s) 1-9 and 17 are so broad as to encompass all possible peptides comprising at least 8 contiguous amino acids of SEQ ID NO 1 or a variant of SEQ ID NO 1, wherein said peptide entirely consists of d-amino acids; optionally further conjugated at the N-terminus with a mitochondrial (mt)-targeting sequence. The scope of the claims is not commensurate with the enablement provided by the disclosure with regard to the extremely large number of peptides and variants broadly encompassed by the claims. The claims rejected under this section of U.S.C. 112, first paragraph, place minimal structural limits on the peptides encompassed by the claims. Since the amino acid sequence of a protein determines its structural and functional properties, predictability of which changes can be tolerated in a protein's amino acid sequence and obtain the desired activity requires a knowledge of and guidance with regard to which amino acids in the protein's sequence, if any, are tolerant of modification and which are conserved (i.e. expectedly intolerant to modification), and detailed knowledge of the ways in which the peptides' structure relates to its function. However, in this case the disclosure is limited to that peptide comprising at least 8 contiguous amino acids of SEQ ID NO 1, wherein said peptide entirely consists of d-amino acids.
While recombinant and mutagenesis techniques are known, it is not routine in the art to screen for multiple substitutions or multiple modifications, as encompassed by the instant claims, and the positions within a peptide's sequence where amino acid modifications can be made with a reasonable expectation of success in obtaining the desired activity/utility are limited in any protein and the result of such modifications is unpredictable. In addition, one skilled in the art would expect any tolerance to modification for a given peptide to diminish with each further and additional modification, e.g. multiple substitutions.
The specification does not support the broad scope of the claims which encompass any possible peptides comprising at least 8 contiguous amino acids of SEQ ID NO 1 or a variant of SEQ ID NO 1, wherein said peptide entirely consists of d-amino acids; optionally further conjugated at the N-terminus with a mitochondrial (mt)-targeting sequence, because the specification does not establish: (A) regions of the peptides which may be modified effecting the desired activity; (B) the general tolerance of peptides to modification and extent of such tolerance; (C) a rational and predictable scheme for modifying any amino acid residue of the peptides with an expectation of obtaining the desired biological function; and (D) the specification provides insufficient guidance as to which of the essentially infinite possible choices is likely to be successful. Because of this lack of guidance, the extended experimentation that would be required to determine which substitutions would be acceptable to retain the required peptides activities and the fact that the relationship between the sequence of a peptide and its tertiary structure (i.e. its activity) are not well understood and are not predictable (e.g., see Ngo et al. in The Protein Folding Problem and Tertiary Structure Prediction, 1994, Merz et al. (ed.), Birkhauser, Boston, MA, pp. 433 and 492-495; Franceus et al., J. Ind. Microbiol. Biotechnol. Vol 44, pp 687-695, 2017), it would require undue experimentation for one skilled in the art to arrive at the majority of those peptides of the claimed genus.
Thus, 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 broadly including any peptides comprising at least 8 contiguous amino acids of SEQ ID NO 1 or a variant of SEQ ID NO 1, wherein said peptide entirely consists of d-amino acids; optionally further conjugated at the N-terminus with a mitochondrial (mt)-targeting sequence. 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 those peptides 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.
(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 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Heavner et al. (US Patent No. 5,753,628).
Heavner et al. (US Patent No. 5,753,628) disclose peptide inhibitors of TNF containing predominantly D-amino acids. Heavner et al. specifically disclose an 8 amnio acid peptide wherein each of the 8 amino acids are D amino acids (see claim 1 and supporting text of Heavner et al.). Thus Heavner et al. teaches a peptide comprising at least 8 contiguous amino acids of SEQ ID NO 1 or a variant of SEQ ID NO 1, wherein said peptide entirely consists of d-amino acids.
Thus claim(s) 1 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Heavner et al. (US Patent No. 5,753,628).
Additional Prior Art not used in a rejection.
WO 2012/089857 A1 discloses peptides from the C-terminal domain of a mitochondrial leucyl-tRNA synthetase comprising a peptide of SEQ ID NO:1 as claimed and its use in the treatment of mitochondrial diseases. The beneficial effect of these peptides includes suppression of the respiratory defect arising from mutation in the mitochondrial gene for a tRNA-leucine.
Remarks
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RICHARD G HUTSON whose telephone number is (571)272-0930. The examiner can normally be reached 6-3 EST Mon-Fri.
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rgh
10/31/2024
/RICHARD G HUTSON/Primary Examiner, Art Unit 1652
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