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 .
DETAILED ACTION
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 8/21/2025 has been entered.
Claim Status
Claims 39-44 and 46-59 are pending. Claims 39, 44, 49 and 58 have been amended. In the response to the restriction requirement, Applicants elected SEQ ID NO: 80 (1st synthetic peptide), maleimide (1st dimerization domain), SEQ ID NO: 83 (2nd synthetic peptide), thiol (2nd dimerization domain), AMAS (moiety formed by the 1st and 2nd dimerization moieties), and
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Applicants elected species was deemed to be free of the prior art. In accordance with Markush Practice, the search was extended to the Markush group/independent claim, and a reference was discovered that rendered it obvious. As a result, claims 39-41, 44 and 49 have been examined and claims 42-43, 46-48 and 50-59 are withdrawn from consideration. While applicant’s elected species may read on one or more withdrawn claims, they have not been fully examined for patentability, and thus a determination of allowability cannot be made with respect to these claims at this time. This is proper, as MPEP 803.02 states that, in these circumstances, the prior art search, however, will not be extended unnecessarily to cover all nonelected species (MPEP 803.02).
Claim Rejections - 35 USC § 102
The rejection of claims 39-41, 44 and 49 under 35 U.S.C. 102(a)(1) as being anticipated by Verdine et al. is withdrawn in view of the amendments to the claims.
Claim Rejections - 35 USC § 103
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 is a new rejection.
Claims 39-41, 44 and 49 are rejected under 35 U.S.C. 103 as being unpatentable over Wolfe et al. (Structure 2000, 8:739-750) in view of Verdine et al. (WO 2011/008260).
With respect to claims 39 and 49, Wolfe et al. teach constructs comprising a Zif268-cJun fusion and TAT-cFos fusion that were designed to form homodimers (para bridging pages 745-746), and further teach that “[t]he cFos and cJun leucine zippers were chosen because they have a strong (100-fold) preference for the formation of heterodimers over homodimers. The Zif23–cJun fusion contained fingers 2 and 3 of Zif268, a junction sequence from the Zif23–GCN4(–2) selection, and the cJun leucine zipper. The TATA23–cFos fusion was analogous but contained the leucine zipper of cFos and fingers 2 and 3 of a zinc finger protein that had been selected to recognize a TATA binding sequence (page 746, left column, 1st para).
Wolfe et al. also teach that “[B]y itself, TATA23–cFos did not bind to this site, and Zif23–cJun bound weakly, but a mixture of the two proteins formed a stable complex with an apparent dissociation constant of 4.3 nM (Figure 8b). Binding of these proteins to the DNA was cooperative, and the mobility of the shifted complex was consistent with the formation of a dimer (page 746, right column, 1st para).
Wolfe et al. do not teach: 1) the claimed moiety formed by the first and second dimerization moieties; and 2) that the peptides comprise at least one internal hydrocarbon staple.
Verdine et al. teach a bifunctional stapled peptide comprising a targeting domain (i.e. a first peptide); a linker moiety; and an effector domain (i.e. a second peptide) (claim 1), wherein both domains are stapled (claim 2), and wherein the bifunctional stapled peptide (i.e. a dimer) binds to DNA (see Figs. 17-22).
Verdine et al. also teach that both domains comprise the following formula (claims 6-7):
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Verdine et al. further teaches the following compound (Fig. 12):
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Verdine et al. further teach that “peptide stapling” is a term coined for a synthetic methodology used to covalently join two olefin-containing side chains present in a polypeptide chain using an olefin metathesis reaction. Stapling of a peptide using a hydrocarbon cross-linker created from an olefin metathesis reaction has been shown to help maintain a peptide's native conformation, particularly under physiological conditions (para [0005]).
It would have been obvious to one of ordinary skill in the art to staple the peptides of Wolfe et al., by using the moiety of Verdine et al., to help maintain the peptides’ native conformation under physiological conditions.
The skilled artisan would have been motivated to do so, with a reasonable expectation of success, because Verdine et al. teach that stapling of a peptide using a hydrocarbon cross-linker created from an olefin metathesis reaction has been shown to help maintain a peptide's native conformation, particularly under physiological conditions.
With respect to claim 40, Verdine et al. teach that “peptide stapling” is a term coined for a synthetic methodology used to covalently join two olefin-containing side chains present in a polypeptide chain using an olefin metathesis reaction. Stapling of a peptide using a hydrocarbon cross-linker created from an olefin metathesis reaction has been shown to help maintain a peptide's native conformation, particularly under physiological conditions (para [0005]).
With respect to claim 41, Verdine et al. teach that the linkage is N-terminus to N-terminus, the linkage is C-terminus to N-terminus, the linkage is C-terminus to C-terminus, or the linkage is through interior amino acids of one or both peptides (para [00337]).
With respect to claim 44, Verdine et al. teach that one peptide comprises a maleimide, whereas the other peptide comprises a thiol (see Fig. 27). Thus, a dimer is formed from the reaction between said thiol and maleimide.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP §§ 706.02(l)(1) - 706.02(l)(3) for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
This is a new rejection.
Claims 39-41, 44 and 49 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-56 of U.S. Patent No. 9163330 in view of Wolfe et al. (Structure 2000, 8:739-750).
With respect to claims 39 and 49, Wolfe et al. teach constructs comprising a Zif268-cJun fusion and TAT-cFos fusion that were designed to form homodimers (para bridging pages 745-746), and further teach that “[t]he cFos and cJun leucine zippers were chosen because they have a strong (100-fold) preference for the formation of heterodimers over homodimers. The Zif23–cJun fusion contained fingers 2 and 3 of Zif268, a junction sequence from the Zif23–GCN4(–2) selection, and the cJun leucine zipper. The TATA23–cFos fusion was analogous but contained the leucine zipper of cFos and fingers 2 and 3 of a zinc finger protein that had been selected to recognize a TATA binding sequence (page 746, left column, 1st para).
Wolfe et al. also teach that “[B]y itself, TATA23–cFos did not bind to this site, and Zif23–cJun bound weakly, but a mixture of the two proteins formed a stable complex with an apparent dissociation constant of 4.3 nM (Figure 8b). Binding of these proteins to the DNA was cooperative, and the mobility of the shifted complex was consistent with the formation of a dimer (page 746, right column, 1st para).
Wolfe et al. do not teach: 1) the claimed moiety formed by the first and second dimerization moieties; and 2) that the peptides comprise at least one internal hydrocarbon staple.
‘330 teaches a bifunctional stapled peptide comprising a targeting domain (i.e. a first peptide); a linker moiety; and an effector domain (i.e. a second peptide) (claim 1), wherein both domains are stapled (claim 2).
‘330 also teaches that both domains comprise the following formula (claim 3):
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‘300 further teaches the following compound (Fig. 12):
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‘330 additionally teaches that “peptide stapling” is a term coined for a synthetic methodology used to covalently join two olefin-containing side chains present in a polypeptide chain using an olefin metathesis reaction. Stapling of a peptide using a hydrocarbon cross-linker created from an olefin metathesis reaction has been shown to help maintain a peptide's native conformation, particularly under physiological conditions (column 1, lines 53-57). Please note that it is proper to turn to and rely on the disclosure of a patent application to ascertain what constitutes an obvious modification. This position is supported by the courts. See In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970).
It would have been obvious to one of ordinary skill in the art to staple the peptides of Wolfe et al., by using the moiety of Verdine et al., to help maintain the peptides’ native conformation under physiological conditions.
The skilled artisan would have been motivated to do so, with a reasonable expectation of success, because Verdine et al. teach that stapling of a peptide using a hydrocarbon cross-linker created from an olefin metathesis reaction has been shown to help maintain a peptide's native conformation, particularly under physiological conditions.
With respect to claim 40, ‘330 teaches that “peptide stapling” is a term coined for a synthetic methodology used to covalently join two olefin-containing side chains present in a polypeptide chain using an olefin metathesis reaction. Stapling of a peptide using a hydrocarbon cross-linker created from an olefin metathesis reaction has been shown to help maintain a peptide's native conformation, particularly under physiological conditions (column 1, lines 53-57).
With respect to claim 41, ‘330 teaches that the linkage is N-terminus to N-terminus, the linkage is C-terminus to N-terminus, the linkage is C-terminus to C-terminus, or the linkage is through interior amino acids of one or both peptides (column 70, lines 62-67).
One of ordinary skill in the art would at once envisage the two functional peptides wherein the linkage is through interior amino acids of one or both peptides.
With respect to claim 44, ‘330 teaches that one peptide comprises a maleimide, whereas the other peptide comprises a thiol (see Fig. 27). Thus, a dimer is formed from the reaction between said thiol and maleimide.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SERGIO COFFA whose telephone number is (571)270-3022. The examiner can normally be reached M-F: 6AM-4PM.
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/SERGIO COFFA Ph.D./
Primary Examiner
Art Unit 1658
/SERGIO COFFA/Primary Examiner, Art Unit 1658