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 and Claim Status
Applicants’ amendments and arguments filed 12/5/25 are acknowledged. Any objection or rejection from the 3/28/25 office action that is not addressed below is withdrawn based on the amendments.
Previously, Group 1 and the species of claim 7 were elected.
Claims 1-6 and 8-35 have been canceled.
Claim 7 is being examined.
Priority
The priority information is found in the filing receipt dated 10/28/24.
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.
Claim 7 is 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 7 recites ‘A peptidomimetic’ and then goes on to recite ‘and is a cell permeable activator of p53, and a pharmaceutically acceptable carrier’. It is unclear if the peptidomimetic itself acts as a pharmaceutically acceptable carrier or if the intent is to claim a composition. Claim 7 does not recite a composition, it recites a ‘peptidomimetic’. It is unclear if the ‘and is…’ of the second to last line of claim 7 is describing both the ‘cell permeable activator of p53’ as well as the ability to act as ‘a pharmaceutically acceptable carrier’. Although unclear, the claim has been interpreted as encompassing a composition as described on pages 22-23 of the instant specification and the claim has been interpreted as including no new matter.
Claim Rejections - 35 USC § 103
Claims were previously rejected based on the references cited below. Since the claims have been amended, the rejection is updated to correspond to the instant claims.
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) 7 is/are rejected under 35 U.S.C. 103 as being unpatentable over Zhan et al. (cite 62 of IDS of 1/6/22; ‘Zhan’) in view of Verdine et al. (WO 2010/011313 01-2010; ‘Verdine’).
Zhan teach 12-mer D-peptide antagonists of MDM2 that kill tumor cells and inhibit tumor growth (first paragraph of introduction). Zhan specifically teach the peptide D-PMI-Beta of sequence TAWYANFEKLLR (page 6237 2nd column first paragraph). Zhan teach a double mutant of D-PMI-Beta which incorporates 6F-Trp3 and p-CF3-Phe7 which was named D-PMI-delta (page 6239 first column 2nd complete paragraph; 6-F−Trp3/p-
CF3−Phe7−DPMI-β, termed DPMI-δ of sequence TA(6-F-Trp)YAN(p-CF3-Phe)EKLLR) which displayed ultrahigh affinity (title and abstract). Zhan suggest the peptide as an anticancer therapeutic (conclusion paragraph on page 6239). Zhan teach alpha-helical conformations of the peptides (page 6237 last paragraph of column 1, first complete paragraph on page 6239 and figure 1). Zhan teach the compounds in a composition for assaying (pages 6237-6238 connecting paragraph). Zhan teach the compounds as inhibitors of p53 (abstract).
Zhan does not teach a version of the peptide that includes two staples or one stitch.
Verdine teach that alpha-helices have a propensity for unraveling and forming random coils which are in most cases biologically less active and highly susceptible to proteolytic degradation (section 0002). Verdine teach an approach to stabilize the alpha helix via covalent cross-links that can impart on the peptide the ability to enter cells, increase half-life and increase affinity (sections 0003 and 0227). Verdine teach that ‘stapling can also increase the affinity for a receptor by as much as 103 to 104 fold’ (section 0003 page 2). In figure 3, Verdine shows examples of the peptide where figure 3 shows the use of modified residues at the i, i +4 and i + 4 + 7 positions (figure 3 1st structure). Figure 3 shows that the modified amino acids are based on pentenyl-alanine at position 1 and pentenyl-glycine at position 5 and octenyl-alanine at position 12 (figure 3 1st structure). Verdine teach that methods of stitching or stapling a peptide is known (section 0007). Verdine teach applications in treating cancer (section 0002). Verdine recognizes peptides with amino terminal groups (figure 6 and sections 0029, 0149 and 0154) and recognize varying stereochemistry of the amino acids (section 0154). Verdine teach pharmaceutical compositions (sections 0009, 0182 and 0193).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the teachings of Zhan because Zhan teach a specific peptide (D-PMI-delta) that is known to have alpha-helical portions (page 6237 last paragraph of column 1, first complete paragraph on page 6239 and figure 1) and suggest applications thereof (conclusion paragraph on page 6239). Since Verdine teach an approach to stabilize the alpha helix via covalent cross-links that can impart on the peptide the ability to enter cells, increase half-life and increase affinity (sections 0003 and 0227) one would have been motivated to incorporate the teachings of Verdine. In figure 3, Verdine shows examples of the peptide where figure 3 shows the use of modified residues at the i, i +4 and i + 4 + 7 positions (figure 3 1st structure). Figure 3 shows that the modified amino acids are based on pentenyl-alanine at position 1, pentenyl-glycine at position 5 and octenyl-alanine at position 12 (figure 3). When using such configuration for the D-PMI-delta peptide of Zhan the resulting peptide is of the claimed sequence. Since Zhan teach the compounds in a composition for assaying (pages 6237-6238 connecting paragraph) and Verdine teach pharmaceutical compositions (sections 0009, 0182 and 0193) one would have been motivated to make compositions. One would have had a reasonable expectation of success since Verdine teach that methods of stitching or stapling a peptide is known (section 0007).
In relation to the peptide of claim 7, as discussed above Zhan teach a double mutant of D-PMI-Beta which incorporates 6F-Trp3 and p-CF3-Phe7 which was named D-PMI-delta (page 6239 first column 2nd complete paragraph; 6-F−Trp3/p-CF3−Phe7−DPMI-β, termed DPMI-δ of sequence TA(6-F-Trp)YAN(p-CF3-Phe)EKLLR). Verdine shows examples of the peptide where figure 3 shows the use of modified residues at the i, i +4 and i + 4 + 7 positions (figure 3 1st structure). Figure 3 of Verdine shows that the modified amino acids are based on pentenyl-alanine at positions 1, pentenyl-glycine at position 5 and octenyl-alanine at position 12 (figure 3). When incorporating the modifications of Verdine to the peptide of Zhan the resulting peptide comprises instant SEQ ID NO: 23. Figure 3 of Verdine shows that the modified amino acids are based on pentenyl-alanine at position 1, pentenyl-glycine at position 5 and octenyl-alanine at position 12 (figure 3). Figure 3 of Verdine shows the cross-linked structure.
In relation to the last 2 lines of claim 7, although unclear, the prior art suggest the same compound as claimed so it is interpreted as being able to function as claimed. Verdine teach an approach to stabilize the alpha helix via covalent cross-links that can impart on the peptide the ability to enter cells (sections 0003 and 0227). Zhan teach the compounds in a composition for assaying (pages 6237-6238 connecting paragraph) and Verdine teach pharmaceutical compositions (sections 0009, 0182 and 0193)
Response to Arguments - 103
Applicant's arguments filed 12/5/25 have been fully considered but they are not persuasive.
Although applicants argue that the claims have been amended, the amended claims are addressed above.
Although applicants argue about the ability to cross a cellular membrane in example 5, example 5 on page 42 of the instant specification refers to figure 7a. None of the compounds tested in figure 7a correspond to the compound of claim 7 (the instant compound appears to be named DPMI-delta (1,5,12) see figure 8a). MPEP 716.02(d) recognizes that any unexpected results are to be commensurate in scope with the claimed invention. In addition, figure 7a appears to show an upward trend for all or nearly all compounds tested suggesting cell permeability. Further, Verdine teach an approach to stabilize the alpha helix via covalent cross-links that can impart on the peptide the ability to enter cells (sections 0003 and 0227). MPEP 716.02(c) II recognizes that any expected beneficial results are evidence of obviousness.
Although applicants argue about increased affinity in examples 6 and 8, Verdine teach that ‘stapling can also increase the affinity for a receptor by as much as 103 to 104 fold’ (section 0003 page 2) where 104 is 10000. Verdine teach an approach to stabilize the alpha helix via covalent cross-links that can impart on the peptide the ability to enter cells, increase half-life and increase affinity (sections 0003 and 0227). Thus, it has not been established that any results are truly unexpected.
Applicants own specification describes the binding as follows (last paragraph of page 44): “DPMI-δ(1,5,12) displayed enhanced cellular activity with EC.sub.50 of 4 μM, at 16 hours, a five-fold increase compared to the single stapled peptides. Similar increases in cell permeability for a stitched peptide have been reported earlier”. MPEP 716.02(c) II recognizes that any expected beneficial results are evidence of obviousness.
Although applicants argue that the references individually do not teach the claims, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Although applicants argue that there is no apparent motivation, as set forth in the rejection: “Since Verdine teach an approach to stabilize the alpha helix via covalent cross-links that can impart on the peptide the ability to enter cells, increase half-life and increase affinity (sections 0003 and 0227) one would have been motivated to incorporate the teachings of Verdine.”. Section 0003 of Verdine states: “Stapling can greatly increase in vivo half-life, most likely through binding to human serum albumin, and stapling can also increase the affinity for a receptor by as much as 103-104-fold.”
Although applicants argue about predictability, MPEP 2143.02 recognizes that absolute predictability or conclusive proof of efficacy is not required. The instant claim is a product claim. One would have had a reasonable expectation of success since Verdine teach that methods of stitching or stapling a peptide is known (section 0007).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RONALD T NIEBAUER whose telephone number is (571)270-3059. The examiner can normally be reached M - F 6:30 - 2:30 EST.
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, Melissa Fisher can be reached at 571-270-7430. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
RONALD T. NIEBAUER
Primary Examiner
Art Unit 1658
/RONALD T NIEBAUER/Examiner, Art Unit 1658