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 .
CONTINUING DATA
This application is a 371 of PCT/EP2021/055109 03/02/2021
FOREIGN APPLICATIONS
UNITED KINGDOM 2003062.3 03/03/2020
This office action is in response to Applicant’s amendment submitted September 15, 2015. Claims 25 and 27-45 are pending.
The rejection of claim 27 under 35 U.S.C. 112(d) is withdrawn in view of Applicant’s amendment to include one or two modifications.
The rejection of claims 28, 40, and 36-41 under 35 U.S.C. 112(b) is withdrawn. Broad ranges together with narrow ranges were removed from the claims, and claims 36-41 recite an active step.
The rejection of claim(s) 27 under 35 U.S.C. 102(a)(2) as being anticipated by Ventress is withdrawn because the Ventress peptide has more than one or two modifications from SEQ ID NO:2 or SEQ ID NO:3.
The rejection of claim 27 under 35 U.S.C. 101 is withdrawn because claim 27 no longer encompasses and an all peptides.
The following rejections of record are maintained and modified for Applicant’s amendment.
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 25 and 28-45 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.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed by him. The courts have stated:
“To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that “the inventor invented the claimed invention.” Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997); In re Gostelli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (“[T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed.”). Thus, an applicant complies with the written description requirement “by describing the invention, with all its claimed limitations, not that which makes it obvious,” and by using “such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention.” Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966.” Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
Further, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. The MPEP states that for a generic claim the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. MPEP § 2163. If the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. See MPEP § 2163. Although the MPEP does not define what constitute a sufficient number of representative species, the courts have indicated what do not constitute a representative number of species to adequately describe a broad generic. In Gostelli, the courts determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gostelli, 872, F.2d at 1012, 10 USPQ2d at 1618.
The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the Application. These include “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. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient.” MPEP § 2163. While all of the factors have been considered, a sufficient amount for a prima facie case are discussed below.
Claim 25 recites an amino acid sequence having at least 85% sequence identity to SEQ ID NO: 1. SEQ ID NO: 1 itself contains 15 residues, four of which can be any amino acid. There are 20 common naturally occurring amino acids found in nature, which implies that (204) 160,000 peptides are claimed even before the 85% sequence identity is taken into account and before the language “comprising” up to five additional amino acids is taken into account. Considering the five additional amino acids (209), the examiner calculates 512000000000 possible peptides. A very large number of peptides can be considered to be within the scope of claim 25, even before the 85% sequence identity is taken into account. The specification (page 16) discloses that seven synthetic peptides were made, and that they did not all have activity. Seven peptides having different activity cannot possibly support a genus of at least 512000000000 different peptides, because small changes in the peptide result in changes in activity. Claim 25 can be considered to recite a partial chemical structure, but a known or disclosed correlation between structure and function is not disclosed and chemical properties could not be predicted for all the various substitutions which are within the scope of the claim, so the skilled artisan would not be apprised that the inventors had possession of the full scope of the claim.
Claim 45 recites a peptide having an amino acid sequence of at least 90% sequence identity to SEQ ID NO: 1. SEQ ID NO: 1 itself contains 15 residues, four of which can be any amino acid. There are 20 common naturally occurring amino acids found in nature, which implies that (204) 160,000 peptides are claimed even before the 90% sequence identity is taken into account. Seven peptides having different activity cannot possibly support a genus of at least 160,000 different peptides, because small changes in the peptide result in changes in activity.
Claim 25 recites that the stability and/or the activity of the peptide is increased compared to a peptide consisting of any one of SEQ ID NO: 5, 6, or 7. Pages 16-17 of the specification states that SEQ ID NO: 3 and SEQ ID NO: 3 had increased potency or stability, but it is not clear which other peptides would show increased potency or stability, so the skilled artisan would not be apprised that the inventors had possession of the full scope of the claim.
Response to Arguments
Applicant argues that claim 25 specifies a core protein structure as well as equivalent variants which can be predicted with a reasonable degree of certainty. This argument is not persuasive because the current specification shows that small changes in the structure of peptides within the scope of claim 25 provide different results. Thus, they are not all equivalent variants.
Applicant argues that the claims provide a correlation between structure and function. That correlation appears to be the stapling, which provides additional stability. This argument is not persuasive because the rejection is based on the number of peptides and possible substitutions, and the correlation between peptide sequence and function is not clear.
Applicant argues that it can be reasonably inferred that variants showing a high degree of sequence similarity to the claimed sequences would exhibit the claimed technical effect. This argument is not persuasive because the examples in the specification illustrate that not all variants having sequence similarity exhibit the claimed effect.
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.
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) 25 and 27-45 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ventress (PLoS ONE 11(7): e0160387, 2016, cited on IDS) in view of Lau (Chem. Soc. Rev., 2014,00, 1-12) and Migon (The Protein Journal (2018) 37:2-12, cited on IDS).
Ventress teaches the peptide 800: EPQRETLKAIHYALN. See Figure 2. The peptide is used for treating human skin and wound infection, particularly S. aureus (see abstract).
Peptide 800 does not contain D at the beginning of the sequence, but claim 25 is drawn to an amino acid sequence having at least 85% sequence identity to SEQ ID NO:1, which includes more than only one difference.
Ventress’s peptide does not comprise at least one staple.
Lau teaches that the native alpha-helical peptide is a clear starting point for designing a mimetic, but the peptide itself usually does not retain the native conformation and binding capability, as it lacks the structural reinforcement provided by the remainder of the protein. One of the most established methods for generating alpha-helices is peptide stapling, wherein two amino acids are chosen which lie on the same face of the helix. These two residues are substituted for non-native amino acids which have side-chains that can be covalently ‘stapled’ together. The length and position of the covalent staple is optimized to impart structural rigidity to the peptide and reinforce the desired alpha-helical conformation. See Introduction.
Migon teaches that antimicrobial peptides are promising candidates for anti-infective pharmaceuticals and are applied topically. Peptide hydrocarbon stapling is a modification for stabilizing protein structure which has been applied to many peptides and gives the peptides improved drug-like properties. See abstract. In practice, two residues need to be located at i and i + 3, i + 4 (one-loop staple), i + 7 (two-loop staple) or i + 11 (three-loop staple) positions since alpha-helix has 3,6 residues per turn. Introduction of two staples may enhance protease resistance, improve pharmacokinetic properties and biological activities. Page 3, first column.
It would have been obvious to one of ordinary skill in the art at the time the application was filed to modify Ventress’s peptide to comprise at least one staple because protein stapling improves stability, pharmacokinetic properties, and biological activities. Ventress’s peptide is an antimicrobial peptide and stapling has been used for enhancing the activity of antimicrobial peptides, as taught by Migon. Migon provides guidance for the position of the staples, so the skilled artisan would have prepared a peptide with staples at the idea position to impart structural rigidity to the peptide and reinforce the desired alpha-helical conformation. It would have been further obvious to administer the peptide along with a antimicrobial drug because the peptide is also an antimicrobial. See MPEP 2144.06: “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose…[T]he idea of combining them flows logically from their having been individually taught in the prior art.”
The limitation of claim 43 is an inherent property of the stapled peptide.
Response to Arguments
Applicant argues that the skilled artisan would not modify the Ventress peptide because there is no mention in Ventress that the peptide 800 adopts an alpha helical conformation. This argument is not persuasive because Lau teaches that the alpha-helix is a common secondary structure motif, that an alpha helical conformation is desirable, and that peptide stapling is “one of the most established methods for generating alpha-helices.” Figure 2 of Lau illustrates a peptide which is not in an alpha helical conformation and then is in an alpha helical conformation after stapling. Migon teaches that constraining the secondary structure of peptides has been proven to increase their biological activity. Thus, the cited references provide motivation to prepare stapled peptides.
Applicant argues that Migon’s peptides prevent and treat bacterial infection by a different mechanism than Ventress’s peptide. This argument is not persuasive because both Lau and Migon teach that stapling generally is desirable and improves biological activity of peptides.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAYLA D BERRY whose telephone number is (571)272-9572. The examiner can normally be reached 7:00-3:00 CST, M-F.
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/LAYLA D BERRY/Primary Examiner, Art Unit 1693