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 1-25, 37, 62-63, 67, 94, and 106-108, of record 1/20/2023, are pending.
Election/Restrictions
Applicant’s election without traverse of group I, claims 1-25, in the reply filed on 11/21/2025 is acknowledged.
Claims 37, 62-63, 67, 94, and 106-108 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 11/21/2025.
Claims 1-25 are under examination.
Priority
The instant application is a national stage entry of PCT/US2021/042418 (filed 7/20/2021), which claims benefit of provisional application 63/054215 (filed 7/20/2020).
Claim Interpretation
The limitation “peptide” is interpreted as being interchangeable with “protein”, consistent with ¶0094 of the instant specification’s PG Pub.
Claim Objections
Claims 1, 9, 15, 17, 19, and 23 are objected to because of the following informalities:
The words “genetically engineered” should be inserted in front of “bacteriophage” in line 2 of claim 1, line 2 of claim 9, line 2 of claim 15, line 2 of claim 17, and lines 2-3 of claim 19.
Additionally, lines 2-3 of claim 9 should be rewritten as “wherein the bacteriophage is a Ff type M13, fd, f1, or ZJ/2 filamentous bacteriophage”.
In claim 23, the limitation “is different as” in line 3 should be replaced with “is different from” or the like.
Appropriate correction is required.
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 1-25 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 1 recites a genetically engineered bacteriophage comprising a plurality of peptides expressed at the surface of the bacteriophage, wherein each peptide comprises two or more cysteine residues. It is unclear whether the plurality of peptides is intended to constitute the genetically engineered aspect of the bacteriophage or whether the claims encompass any genetically engineered bacteriophage expressing two or more endogenous surface proteins that comprise two or more cysteine residues. Dependent claims 2-25 are included in the rejection.
Claim 25 recites the limitation "the two or more structurally and/or functionally distinct populations of peptides" in line 2. There is insufficient antecedent basis for this limitation in the claim.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-2, 5, and 8-9 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lee et al. (Science, 2002).
Lee et al. teach the formation of a composite material from genetically engineered bacteriophages and zinc sulfide nanocrystals (See Abstract).
Regarding claims 1-2, 5, and 8-9: Lee et al. teach an M13 (which reads on “filamentous”) bacteriophage comprising pIII coat proteins with a peptide insert sequence of CNNPMHQC (which reads on “plurality of peptides expressed at a surface of the bacteriophage” and “each peptide comprises a CX(X)nC… motif, wherein n is 1, 2, 3, 4, 5, 6, 7, or 8”) (See page 892, col. 3, full ¶1-2). The cysteine residues form a disulfide bond that restricts the peptide structure to a constrained loop (See page 892, col. 3, full ¶1).
Claims 1-5, 8-9, 11-13, and 15-19 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Ploegh et al. (US 20140030697 A1).
Ploegh et al. teach viral particles comprising proteins with sortase recognition motifs (See Abstract).
Regarding claims 1--5, 8-9, 11-13, and 15-19: Ploegh et al. teach an M13 (which reads on “filamentous”) bacteriophage comprising recombinant capsid proteins, which can be pIII and/or pVIII, comprising a sortase recognition motif, which can be placed at the capsid protein’s N-terminus (which reads on “plurality of peptides expressed at a surface of the bacteriophage” and “protease-cleavable amino acid sequence”) (See ¶0009-0010 and 00020). The sortase recognition motif can be flanked by two cysteine residues that form a disulfide bond to create a loop structure (See ¶0010). Suitable recognition motifs include LPETG and LPETA (which read on “each peptide comprises a CX(X)nC… motif, wherein n is 1, 2, 3, 4, 5, 6, 7, or 8”) (See ¶0007). Ploegh et al. teach that a plurality of different viral capsid proteins can be specifically functionalized using different sortase recognition motifs (which reads on “the plurality of peptides are structurally substantially the same or have a similar function” and “the bacteriophage further comprises at least one different plurality of peptides expressed at the surface of the bacteriophage”) (See ¶0106 and 0143). In embodiments, a bacteriophage can comprise one capsid protein modified with a Streptococcus aureus sortase recognition motif and another capsid protein modified with a Streptococcus pyogenes sortase recognition motif (See ¶0006). The peptide loop structure between the two cysteines can also be a protease-sensitive amino acid sequence derived from a bacterial toxin or an oligoglycine or oligoalanine sequence (which reads on “structurally and/or functionally distinct populations of peptides”) (See ¶0007 and 0010). 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).
Claims 1, 3-9, and 12 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Casey (Doctoral dissertation, 2015)
Casey teaches a bacteriophage platform featuring viral capsid proteins with catalytic activity (See Abstract).
Regarding claims 1, 3-9, and 12: Casey teaches M13 (which reads on “filamentous”) bacteriophages engineered to comprise 8-amino acid inserts at the N-terminus of pVIII (which reads on “plurality of peptides expressed at a surface of the bacteriophage”) (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).
Claims 1 and 9-10 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Arai et al. (Bioorganic & Medicinal Chemistry Letters, 2013).
Arai et al. teach monosaccharide-modified peptide phage display libraries (See Abstract).
Regarding claims 1 and 9-10: Arai et al. teach a fd (which reads on “filamentous”) bacteriophage library for displaying mannose-modified (which reads on “glycosylated”) peptides (which reads on “plurality of peptides expressed at a surface of the bacteriophage”) (See page 4940, col. 2, full ¶1 and page S5, full ¶1). Clones 15-18 comprise the peptide sequences ACCGD, VACCR, EECCH, and SKCCK, respectively (which read on “two or more cysteine residues”) (See page 4941, col. 1, ¶1 and table S1).
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 1-5, 8-9, 11-12, 15-19, and 20-24 are rejected under 35 U.S.C. 103 as being unpatentable over Ploegh et al. (US 20140030697 A1).
The teachings of Ploegh et al. are set forth in the rejection above and are incorporated herein in their entirety.
Regarding claims 20-24: Following the discussion of claims 1-5, 8-9, 11-12, and 15-19, Ploegh et al. teach an M13 bacteriophage comprising an N-terminal disulfide-bonded peptide-modified pIII, pVIII or pIX capsid protein (See ¶0006-0007, 0009-0010, and 0110), but they do not expressly teach the a bacteriophage comprising different peptides at the N-terminus of the pIII, pVI, pVII, and/or pIX capsid proteins.
However, 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 pIII, pIX, pVI and/or pVIII coat proteins in the bacteriophage of Ploegh et al. to comprise N-terminal sortase motifs flanked by two cysteines, wherein they are conjugated to the same or different proteins. One would be motivated to make these modifications because Ploegh et al. suggest that either terminus of the M13 capsid proteins can accommodate peptides and that multiple different capsid proteins of a bacteriophage can be modified with multiple different peptides (See ¶0010-0011, 0097, and 0110). Such modifications could be readily performed by one of ordinary skill in the art.
Claims 1-5, 8-9, and 11-25 are rejected under 35 U.S.C. 103 as being unpatentable over Ploegh et al. (US 20140030697 A1) in view of Casey (Dissertation, 2015).
The teachings of Ploegh et al. and Casey are set forth in the rejections above and are incorporated herein in their entirety.
Regarding claims 13-14 and 20-25: Following the discussion of claims 1-5, 8-9, 11-12, and 15-19, Ploegh et al. teach M13 bacteriophages with capsid proteins comprising a disulfide-constrained peptides (See ¶0010). Ploegh et al. also teach that different peptides can be expressed on the 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). However, Ploegh et al. do not expressly teach that the different peptides function in tandem, sequentially, or in a cascade.
Casey teaches M13 comprising a N-terminus peptide insertion in pVIII and 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).
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 of Ploegh et al. to comprise complementary binding or catalytic functions on different capsid proteins via peptides having different motifs within disulfide-constrained loops. One would be motivated to make this modification because Casey suggests that functional variants could be generated in this manner (See page 97, ¶1). There would be a reasonable expectation of success in doing so because Casey teaches that the M13 genome comprises numerous restriction cleavage sites in its various coat protein genes for peptide insertion (See 97, ¶1).
Conclusion
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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/J.S.S./Examiner, Art Unit 1633
/CHRISTOPHER M BABIC/Supervisory Patent Examiner, Art Unit 1633