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
Applicant’s election without traverse of Group I, drawn to peptides comprising SEQ ID NO: 1, claimed in claims 1, 6, 9, 32, 46, 60-63,66, 69, 71, 74, 87 and 116 in the reply filed on 7/10/26 is acknowledged. Election was made without traverse of SEQ ID NO: 26. Applicants state that claims 32 and 60-63 read on the elected species. However, claim 60, which recites SEQ ID NO: 26 depends from claim 1 (not claim 32). Importantly, claim 1 does not read on the elected SEQ ID NO: 26 because it does not contain the required substitution as F3, G18 or G21 and is therefore withdrawn from consideration. Claims 60-61 depend from withdrawn claim 1 and are therefore also withdrawn. Claims 32 and 62-63 read on the elected species. Accordingly, claims 1,6, 9, 38,46, 60-61, 64-66, 69, 71,74,87-88,114 and 116 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected group, there being no allowable generic or linking claim.
Claims 32 and 62-63 read on the elected species and are under consideration.
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 32 is 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. The specification does not provide a representative number of species to support the genus claimed. While there is support for the StAMPs reduced to practice (SEQ ID NO: 2-45 with an (alk) crosslink), there is no support for the complete claimed genus of variations SEQ ID NO: 1 with any type of crosslink. A detailed analysis is below.
Claim 32 recites a peptide comprising SEQ ID NO: 1 or a pharmaceutically acceptable salt thereof, wherein X1, X2, X3, and X4 are independently amino acids, wherein X1 and X2 are connected via a crosslink, and X3 and X4 are connected via a crosslink or X1 and X2 each independently comprise a reactive moiety capable of forming a crosslink with the other and X3, and X4 each independently comprise a reactive moiety capable of forming a crosslink with the other; and the amino acid sequence includes 1 to 8 amino acid substitutions, inclusive, at positions other than X1, X2, X3, and X4; provided that at least one amino acid is substituted by K, Dab, Orn, Dap, R or hArg. does not support that the inventors, at the time of filing, possessed the complete recited genus.
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 inventor was in possession of the claimed genus [MPEP 2163 ii)].
The MPEP also states that the representative number of species means that the species which are adequately described are representative of the entire genus and when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. In the instant case, the specification and claims provide representative species of 2-45 with an (alk) crosslink. The instant specification states that the peptides are StAMP species for broad-spectrum Gram-negative antimicrobial activity and selectivity over renal and hepatic cells (p. 84-85, Tables A-C). However, sequences reduced to practice by the applicant are not representative of the entire genus of claimed.
The sequence claimed comprises of a minimum of 21 residues, and 8, of which can be substituted with any amino acid (as long as one amino acid is substituted with K, Dab, Orn, Dap, R or hArg). The substitutions can occur at any position of the peptide. If one considers that there are 20 natural amino acids and a great number of non-natural amino acids and the peptide can comprise 8 substitutions at any position, the number of peptides that can meet the structural limitations of the claim is enormous. The limited number of examples is not representative of this great variation. Furthermore, the claimed StAMPs can have X1 and X2 and X3 and X4 forming any type of crosslink or amino acids that are capable of forming a crosslink. There is substantial variation within the genus, and SEQ ID NO: 2-45 with an ank crosslink are not representative of the genus because the genus is quite large. Importantly, it is established that a single amino acid substation can affect the function of the protein or peptide (Ng & Henikoff (2006)).
In conclusion, for the reasons presented above, the skilled artisan would reasonably conclude that the inventors, at the time the application was filed had full possession of the neuropeptide analogs, SEQ ID NO: 2-45.
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 32 and 62-63 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 32 recites “the amino acid sequence includes 1 to 8 amino acid substitutions, inclusive at position other than X1, X2, X3 and X4”. This limitation is indefinite because the intended scope of the term “inclusive” is unclear. It is unclear whether a total of 8 substitutions are allowed in the sequence with none of them occurring at X1, X2, X3 and X4 or if up to 8 substitutions are allowed in the sequence while also permitting substitutions at X1, X2, X3 and X4 (so a total of 12 substitutions are allowed). The number of substitutions and the position at which those substitutions can occur are unclear. Therefore, it is impossible to determine the metes and bounds of the claims.
Claims 62-63 are rejected for depending from claim 32 and not corrected the deficiencies.
Claim Rejections - 35 USC § 103
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 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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 32 and 62 are rejected under 35 U.S.C. 103 as being unpatentable over Mourtada et al. (Mourtada, R., Herce, H.D., Yin, D.J. et al. Design of stapled antimicrobial peptides that are stable, nontoxic and kill antibiotic-resistant bacteria in mice. Nat Biotechnol 37, 1186–1197 (2019)).
Mourtada et al. analyze a 58-member library of stapled AMPs (StAMPS) based on magainin II, pleuroidin, Cap18 and esculentin and apply the insights from structure-function-toxicity measurements to devise an algorithm for the design of stable, protease-resistant, potent, and nontoxic StAMP prototypes (Abstract). Mourtada et al. teach the StAMP based on esculentin of:
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31
262
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The sequence above meets the limitation of SEQ ID NO: 1, wherein X1, X2, X3 and X4 are connected via a crosslink. Mourtada et al. does not teach the peptide above with at least one of the amino acids is substituted by Lys. However, the teachings of Mourtada et al. are suggestive of the limitation.
Mourtada et al. teach optimization of the stapled peptides by lysine scanning, wherein lysine is sequentially introduced along the peptide helix to evaluate the effect of the substitution on antimicrobial activity and hemolytic activity (p. 1187, 2nd col. 2nd para.).
With respect to claim 32 and 62-63, it would have been obvious to a person of ordinary skill in the art to modify the peptide disclosed by Mourtada et al. by substituting the N-terminal G with lysine thereby arriving at instantly claimed SEQ ID NO: 35. Mourtada et al. teach the use of lysine scanning to optimize the stapled antimicrobial peptides, which includes sequential introduction of lysine at positions along the peptide sequence. Therefore, a person of ordinary skill in the art would have been motivated to substitute K for the N-terminal G of SEQ ID NO: 1, resulting in instantly claimed SEQ ID NO: 35. There is a reasonable expectation of success given that lysine scanning is a method routinely used in the art.
Claim 63 is rejected under 35 U.S.C. 103 as being unpatentable over Mourtada et al. as applied to claims 32 and 62 above, and further in view of Mahlapuu et al. (Antimicrobial Peptides: An Emerging Category of Therapeutic Agents; Front Cell Infect Microbial. 2016 Dec. 27;6:194).
The teachings of Mourtada et al. are presented above. The reference do not teach the C-terminus of SEQ ID NO: 35 is amidated. However, the teachings of Mahlapuu et al. cure this deficiency.
Mahlapuu et al. teach that blocking N or C terminal ends of AMPs by modifications such as C-terminal amidation is frequently used to increase resistance toward peptidases (top of p. 19).
It would have been obvious to a person of ordinary skill in the art to C-terminally amidate the peptide of Mourtada et al. in order to increase the stability of the peptide. There is a reasonable expectation of success given that amidation of peptides is routine in the art.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TARA L MARTINEZ whose telephone number is (571)270-1470. The examiner can normally be reached Mon-Fri 8:00-5:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lianko Garyu can be reached at (571)270-7367. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/TARA L MARTINEZ/Primary Examiner, Art Unit 1654
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