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, 4, 7-25, 37, 62-63, 67, 94, and 106-108, of record 4/13/2026, are pending and subject to prosecution. Claims 1, 7-9, 15, 17, 19, and 23 are amended. Claims 2-3 and 5-6 are cancelled. Claims 37, 62-63, 67, 94, and 106-108 remain withdrawn.
Status of Prior Objections/Rejections
RE: Objection to claims 1, 9, 15, 17, 19, and 23:
The amendment to claims 1, 9, 15, 17, 19, and 23 is effective to obviate the objection. The objection is withdrawn.
RE: Rejection of claims 1-25 under 35 U.S.C. 112(b):
The cancellation of claims 2-3 and 5-6 renders the rejection thereto moot.
The amendment to claim 1 to require that the genetically engineered bacteriophage is modified to express the plurality of peptides is effective to obviate the rejection. The rejection is withdrawn.
RE: Rejection of claims 1-2, 5, and 8-9 under 35 U.S.C. 102(a)(1) over Lee et al. (Science, 2002):
RE: Rejection of claims 1-5, 8-9, 11-13, and 15-19 under 35 U.S.C. 102(a)(1) and 102(a)(2) over Ploegh et al. (US 20140030697 A1):
RE: Rejection of claims 1, 3-9, and 12 under 35 U.S.C. 102(a)(1) over Casey (Doctoral dissertation, 2015):
RE: Rejection of claims 1 and 9-10 under 35 U.S.C. 102(a)(1) over Arai et al. (Bioorganic & Medicinal Chemistry Letters, 2013):
RE: Rejection of claims 1-5, 8-9, 11-12, 15-19, and 20-24 under 35 U.S.C. 103 over Ploegh et al. (US 20140030697 A1):
RE: Rejection of claims 1-5, 8-9, and 11-25 under 35 U.S.C. 103 over Ploegh et al. (US 20140030697 A1) in view of Casey (Dissertation, 2015):
The cancellation of claims 2-3 and 5-6 renders the rejections thereto moot.
The amendment to claim 1 to require that the peptides comprise a CXXC motif, form intrapeptide disulfide bonds, and are displayed proximate to the N-terminus of pVIII coat proteins is effective to obviate the rejections. The rejections are withdrawn.
New Objections/Rejections
Claim Objections
Claim 8 is objected to because of the following informalities:
In line 5 of claim 8, “praline” should be replaced with “proline”.
Appropriate correction is required.
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.
Claims 1, 4, 7-9, 12-14, and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Casey (Doctoral dissertation, 2015), of record, in view of Iqbalsyah et al. (Protein Science, 2006).
Regarding claims 1, 4, 7-9, and 12: Casey teaches M13 (which reads on “filamentous”) bacteriophages engineered to comprise 8-amino acid inserts with catalytic activity at the N-terminus of pVIII (which reads on “plurality of peptides at a surface of the bacteriophage”, “displayed proximate to the N terminus of a plurality of pVIII major coat proteins”, and “each peptide further comprises a pVIII major coat protein”) (See page 26, full ¶3). Casey teaches protein-binding clones comprising the insert sequence SCPDCGAE (which reads on “a CX(X)nC… motif, wherein n is 1”, “the CXXC… motif is included in a XCPDCXXX… sequence”, and “the peptides in the plurality of peptides are structurally substantially the same or have a similar function”) (See page 77, full ¶1 and table 4.1). Casey does not expressly teach the cysteine residues as forming an intra-peptide disulfide bond.
Iqbalsyah et al. analyze the structure and energetic properties of a model peptide comprising a CXXC motif (See Abstract). Intra-peptide disulfide bonds are formed readily and rapidly upon solvation of the solid peptide (See page 1946, col. 1, full ¶1-2). Iqbalsyah et al. suggest that the disulfide bond acts to stabilize the N-termini of alpha helices (See page 1949, col. 1, ¶1).
It would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention that the insert sequence taught by Casey, SCPDCGAE, would be likely to similarly engage in intra-peptide disulfide bonding via its CXXC motif, based upon the teachings of Iqbalsyah et al. (See page 1946, col. 1, full ¶1-2). Insertion of the peptide at the helical pVIII N-terminus would leave it solvent-exposed and prone to oxidation, consistent with the behavior of the model peptide taught by Iqbalsyah et al.
Regarding claims 13-14 and 19: Following the discussion of claims 1, 4, 7-9, and 12, Casey teaches that M13 can be engineered so that complementary binding or catalytic functions (which read on “two or more structurally and/or functionally distinct populations of peptides”, “function in tandem, sequentially, or in a cascade”, and “at least one different plurality of peptides expressed at the surface of the bacteriophage”) can be incorporated at other positions on the coat proteins of the capsid (See page 26, full ¶3 and page 97, ¶1).
Claims 1, 4, 7-10, 12-14, and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Casey (Doctoral dissertation, 2015), of record, in view of Iqbalsyah et al. (Protein Science, 2006), further in view of Ng et al. (Peptide Libraries, 2015) and Merril et al. (US 20030026785 A1).
The teachings of Casey and Iqbalsyah et al. are set forth in the rejection above and are incorporated herein in their entirety.
Regarding claim 10: Following the discussion of claims 1, 4, 7-9, 12-14, and 19, Casey, modified by Iqbalsyah et al., render obvious a genetically engineered bacteriophage expressing a peptide-modified pVIII but do not expressly teach glycosylation of the peptide.
Ng et al. teach a method for the post-translational modification of phage-displayed peptides (See Abstract). Peptides displayed on the surface of the M13 bacteriophage were modified to add a mannose group at an N-terminal serine or threonine (which reads on “glycosylated”) (See page 156, full ¶1 and fig. 1).
Merril et al. teach methods for delaying bacteriophage inactivation by host defense systems (See Abstract). Glycosylation of recombinant proteins on bacteriophage surfaces could be used to repel immune cells by their negative charge (See ¶0032-0033).
It would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention to modify the method of Casey, modified by Iqbalsyah et al., to comprise mannosylation of the peptide’s N-terminal serine residue, as taught by Ng et al. One would be motivated to make this modification because Merril et al. suggest glycosylation of bacteriophage surface proteins as a strategy for reducing inactivation by host immune cells (See ¶0032-0033). There would be a reasonable expectation of success in doing so because the bacteriophage of Casey could be readily modified by the method of Ng et al.
Claims 1, 4, 7-9, and 11-25 are rejected under 35 U.S.C. 103 as being unpatentable over Casey (Doctoral dissertation, 2015), of record, in view of Iqbalsyah et al. (Protein Science, 2006), further in view of Ploegh et al. (US 20140030697 A1), of record.
The teachings of Casey and Iqbalsyah et al. are set forth in the rejection above and are incorporated herein in their entirety.
Regarding claims 11 and 15-18: Following the discussion of claims 1, 4, 7-9, 12-14, and 19, Casey, modified by Iqbalsyah et al., render obvious a genetically engineered bacteriophage expressing a peptide-modified pVIII but do not expressly teach the virus as comprising additional moieties.
Ploegh et al. teach an M13 bacteriophage comprising recombinant capsid proteins, which can be pIII and/or pVIII, comprising a sortase recognition motif (which reads on “protease-cleavable amino acid sequence”) (See ¶0009-0010 and 00020). A sortase can be used to attach moieties to the capsid proteins via transpeptidation (See ¶0070). The moiety can be a label (such as firefly or Renilla luciferase, EGFP, EBFP2, TagBFP, mTurquoise, mCherry, mOrange, mOrange2, mRuby, mRaspberry, mKate2, Azurite, and mNeptune) or an enzyme (such as horseradish peroxidase) (See ¶0071). The moiety can be an antibody or antibody fragment, such as an scFv (See ¶0064).
It would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention to modify the bacteriophage rendered obvious by Casey, modified by Iqbalsyah et al., to comprise a sortase recognition motif for attaching one or more of the molecules taught by Ploegh et al. One would have been motivated to make this modification because Ploegh et al. teach that it enables site-specific attachment of a wide range of molecules under physiological conditions for new biological applications (See ¶0144-0145). There would be a reasonable expectation of success in doing so because Plough et al. demonstrate labeling of M13 capsid proteins with biotin and fluorophores via sortase-mediated reactions (See ¶0183-0202).
Regarding claims 20-25: Following the discussion of claims 1, 4, 7-9, 12-14, and 19, Casey, modified by Iqbalsyah et al., render obvious a genetically engineered bacteriophage expressing pVIII comprising multiple different peptides, one of which is N-terminus-proximal and has a disulfide-bonded CXXC motif, that are structurally and/or functionally distinct and can function in tandem, sequentially, or in a cascade. However, Casey and Iqbalsyah et al. do not expressly teach the locations of other peptides on the bacteriophage.
Ploegh et al. teach that different peptides can be expressed on the M13 pIII, pVIII, and/or pIX capsid proteins and that the peptides can be inserted at or near the N- or C-terminus of the capsid proteins (See ¶0006-0007, 0010, 0106, 0110, and 0143).
It would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention to modify the bacteriophage rendered obvious by Casey, modified by Iqbalsyah et al. to comprise the insertion of other peptides at the pIII, pVIII, and/or pIX N- or C-terminus. One would have been motivated to make this modification because the teachings of Ploegh et al. suggest that these sites are all permissive to insertion of heterologous peptides on the bacteriophage (See ¶0006-0007, 0010, 0106, 0110, and 0143), and such a modification could be readily carried out by one of ordinary skill.
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 JENNIFER S SPENCE, whose telephone number is 571-272-8590. The examiner can normally be reached M-F 8:30-5:30.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Christopher M Babic, can be reached at 571-272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/J.S.S./Examiner, Art Unit 1633
/CHRISTOPHER M BABIC/Supervisory Patent Examiner, Art Unit 1633
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