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
Applicant's election without traverse of Group I, corresponding to claims 1 – 15, in the reply filed on 06/15/2026 is acknowledged.
Claims 16, 18, and 20 – 22 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 01/30/2026.
Claims 1 – 15 are under consideration.
Priority
This is a National Stage Entry under 35 U.S.C. 371 of International Patent Application
No. PCT/US2022/033690, filed June 15, 2022. This application also claims priority to US
Provisional Application No. 63/212,018, filed on June 17, 2021.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Examples include: https://www.neb.com/products/e8100-phd-7-phage-display-peptide-library-kit
Claim Interpretation
Claims 1 and 2, recite peptides starting with “N-“ and ending with “-C.” Claim 1 recites “N- GWRVSEL-C”, “N-GWRVSEF-C”, “N-GWRVSE-C”, “N- GFHYSLH-C”, and “N- IVGSQVT-C.” Claim 2 recites “N- GWRVSEL-C”and “N-GWRVSEF-C.” Consistent with the Sequence Listing, “N-” is understood as identifying the N terminus. Similarly, “-C” is understood as identifying the C terminus.
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 8 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.
Regarding claim 8, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention.
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.
Claim(s) 1, 3, 4, 10, and 12 – 15 are rejected under 35 U.S.C. 103 as being unpatentable over Bremel et al (US20130330335A1, hereinafter, “Bremel”), in view of Steinmetz et al (US20190030148A1, hereinafter, “Steinmetz”).
Bremel teaches the identification of peptides binding to ligands (Abstract). Bremel teaches these peptides can be conjugated to carriers for the purpose of treating diseases (¶0275, 0279). Bremel teaches a peptide comprised of one or more epitopes that are conjugated to a carrier protein and that the sequence of the conjugated peptide can be comprised of GWRVSE (reproduced below; sequence 649253, aligned to SEQ ID NO: 3 below; Sequence1 is 649253, Sequence2 is SEQ ID NO: 3). Bremel teaches the peptides can be expressed on viruses or virus-like particles (¶0275).
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Regarding claim 1, Bremel teaches a peptide consisting of DTRRGWRVSEQLETGM. Claim 1 is drawn to a conjugate comprising GWRVSE. Although Bremel teaches a peptide with additional amino acids, peptide 649253 of Bremel reasonably encompasses the peptide of claim 1. Therefore, Bremel teaches a peptide comprised of GWRVSE with 100% sequence identity to SEQ ID NO: 3 (reproduced above). Bremel does not teach the peptide is conjugated to the surface of a cowpea mosaic virus (CPMV) or CPMV coat protein (CP) where in the N-terminus of the peptide is linked to the CPMV or CP surface.
However, Steinmetz a vaccine composition comprising a plant virus particle linked to an HER2 antigen (Abstract). Steinmetz teaches that the plant virus particle can be CPMV (¶0033). Steinmetz teaches that the HER2 antigen can be connected to the plant virus using a linker molecule (¶0042). Steinmetz teaches that the linker can be a short spacer comprising of 2 to 20 amino acids (¶0042). Steinmetz also teaches that attaching antigens to the virus particle on suitable lysines though reactions with a primary amine on the plant virus (¶0043).
Regarding claims 3 and 4, Steinmetz teaches that attaching antigens, such as HER2, to the virus particle on suitable lysine residues though reactions with a primary amine on the plant virus (¶0042, 0043).
Regarding claim 10, Steinmetz teaches HER2 antigens are conjugated to a plant virus particle (¶0041).
Regarding claims 12 and 13, Bremel teaches a plurality of polypeptides are conjugated to the virus (¶0039). Similarly, Steinmetz teaches a plurality of HER2 antigens are linked to the plant virus particle (¶0041).
Regarding claims 14 and 15, Steinmetz teaches a composition comprising of a plant virus particle linked to a HER2 antigen and a pharmaceutically acceptable carriers, such as water (¶0054, 0055).
Bremel and Steinmetz are considered to be analogous to the claim invention because they both aim to treat disease with modified viruses. Bremel teaches a peptide comprised of GWRVSE with 100% sequence identity to SEQ ID NO: 3 (reproduced above). Steinmetz teaches that the HER2 antigen can be connected to the CPMV using a linker molecule (¶0042). Steinmetz also teaches a linker group can serve to increase chemical reactivity of a substituent on either the agent or the virus particle, and thus increase the coupling efficiency, and can also improve the immunogenicity of the linked antigen (¶0042).
. Together, the prior art teaches that a peptide comprising GWRSVE, as well as other peptides, can be conjugated to viruses or viral like protein. Therefore, it would have been prima facie obvious before the effective filing date of the claimed invention to have conjugated a peptide comprising GWRVSE to CPMV because doing so would allow for the further inclusion of peptides while improving immunogenicity. One of ordinary skill in the art would have had a reasonable expectation of success pseudotyping a CPMV with a peptide comprising GWRSVE given that the conjugating the peptide to carriers is well known, has been successfully demonstrated, and commonly used in the prior art.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art at the time of filing especially in the absence of evidence to the contrary.
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Bremel and Steinmetz as applied to claims 1, 3, 4, 10, and 12 – 15 above, and further in view of Aljabali et al (Mol Pharm, 2013, 10.1021/mp3002057, hereinafter, “Aljabali”).
As discussed above, claims 1, 3, 4, 10, and 12 – 15 were rendered prima facie obvious by Bremel and Steinmetz. While the references teach the conjugating of a peptide comprising GWRSVE to a CPMV, the references fail to explicitly further teach active agents conjugated to the exterior of the CPMV by covalent coupling.
However, Aljabali teaches a CPMV that was developed as a carrier for the chemotherapeutic drug, doxorubicin (DOX) (Abstract). Aljabali teaches 80 DOX molecules are covalently bound to the external surface carboxylates of the CPMV (Abstract). Aljabali teaches that the CMPV-DOX shows cytotoxicity in cancer cells at low dosages (Abstract). Aljabali also teaches a mechanism in which the proteinaceous drug carrier is degraded and the drug released (Abstract).
Regarding claim 5, Aljabali teaches multiple DOX was covalently coupled to the CPMV either directly to carboxylate groups on the external surface of native CPMV utilizing the EDC/NHS method or to amine groups on the surface with an eight-atom spacer arm crosslinker containing a central disulfide bond (Results and Discussion ¶1).
Bremel, Steinmetz, and Aljabali are considered to be analogous to the claim invention because they aim to treat disease with modified viruses. Bremel teaches a peptide comprised of GWRVSE with 100% sequence identity to SEQ ID NO: 3 (reproduced above). Steinmetz teaches that the HER2 antigen can be connected to the CPMV using a linker molecule (¶0042). Steinmetz also teaches a linker group can serve to increase chemical reactivity of a substituent on either the agent or the virus particle, and thus increase the coupling efficiency, and can also improve the immunogenicity of the linked antigen (¶0042). Aljabali teaches DOX molecules can be covalently bound to the external surface carboxylates of the CPMV (Abstract).
Together, the prior art teaches that a peptide comprised of GWRVSE can be conjugated to the surface of CPMV and be further comprised of active agents conjugated to the exterior of the CPMV by covalent coupling. Therefore, it would have been prima facie obvious before the effective filing date of the claimed invention to have conjugated a peptide comprising GWRVSE to CPMV as well as DOX because doing so would allow for the delivery of chemotherapeutic drugs while also allowing for further antigen presentation. One of ordinary skill in the art would have had a reasonable expectation of success pseudotyping a CPMV with a peptide comprising GWRSVE and chemotherapeutic drugs given that the conjugating the peptide and chemotherapeutic drugs to carriers is well known, has been successfully demonstrated, and commonly used in the prior art.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art at the time of filing especially in the absence of evidence to the contrary.
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Bremel and Steinmetz as applied to claims 1, 3, 4, 10, and 12 – 15 above, and further in view of Lam et al (J Mater Chem B, 2019, 10.1039/C8TB01191E, hereinafter, “Lam”).
As discussed above, claims 1, 3, 4, 10, and 12 – 15 were rendered prima facie obvious by Bremel and Steinmetz. While the references teach the conjugating of a peptide comprising GWRSVE to a CPMV, the references fail to further teach an agent infused into the CPMV.
However, Lam teaches that mitoxatrone (MTO), an antineoplastic chemotherapeutic, can be delivered in a CPMV (Abstract). Lam teaches that MTO has potent activity against glioblastoma multiforme (Abstract). Lam teaches that MTO can be loaded into the interior cavatiy of CPMV through diffusion through its pores (Abstract). Lam also teaches the uptake of CPMV-MTO by glioma cells and leading to cytotoxic effects (Abstract).
Regarding claim 6, Lam teaches the loading of MTO into CPMV (Section: Loading of mitoxantrone (MTO) into CPMV).
Bremel, Steinmetz, and Lam are considered to be analogous to the claim invention because they aim to treat disease with modified viruses. Bremel teaches a peptide comprised of GWRVSE with 100% sequence identity to SEQ ID NO: 3 (reproduced above). Steinmetz teaches that the HER2 antigen can be connected to the CPMV using a linker molecule (¶0042). Steinmetz also teaches a linker group can serve to increase chemical reactivity of a substituent on either the agent or the virus particle, and thus increase the coupling efficiency, and can also improve the immunogenicity of the linked antigen (¶0042). Lam teaches the loading of MTO into CPMV (Section: Loading of mitoxantrone (MTO) into CPMV).
Together, the prior art teaches that a peptide comprised of GWRVSE can be conjugated to the surface of CPMV and be further comprised of agents carried by the CPMV. Therefore, it would have been prima facie obvious before the effective filing date of the claimed invention to have conjugated a peptide comprising GWRVSE to CPMV and infuse MTO because doing so would allow for the delivery of chemotherapeutic drugs while also allowing for the possibility of improving cell type specificity by further modifications to the virus’s surface. One of ordinary skill in the art would have had a reasonable expectation of success pseudotyping a CPMV with a peptide comprising GWRSVE and infusing the CPMV with chemotherapeutic drugs given that the conjugating the peptide and infusing the CPMV with chemotherapeutic drugs is well known, has been successfully demonstrated, and commonly used in the prior art.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art at the time of filing especially in the absence of evidence to the contrary.
Claims 7 and 8 are rejected under 35 U.S.C. 103 as being unpatentable over Bremel and Steinmetz as applied to claims 1, 3, 4, 10, and 12 – 15 above, and further in view of Gupta et al (Bioconjugate Chemistry, 2005, 10.1021/bc050147l, hereinafter, “Gupta”).
As discussed above, claims 1, 3, 4, 10, and 12 – 15 were rendered prima facie obvious by Bremel and Steinmetz. While the references teach the conjugating of a peptide comprising GWRSVE to a CPMV, the references fail to further teach targeting solvent-exposed lysine side chains using biorthogonal click-chemistry.
However, regarding claim 7 and 8, Gupta teaches the chemoselective attachment of biologically relevant molecules to CPMV (Abstract). Gupta teaches that a CuAAC reaction enables an efficient covalent bond formation of substrates such as sugars, peptides, and polymers (Abstract). Gupta teaches capsids were labeled with alkynes or azides at surface-exposed lysine residues using standard NHS ester chemistry followed by CuAAC to conjugate substrates such as fluorescein dyes (Section: Optimization of Reaction Conditions.).
Bremel, Steinmetz, and Gupta are considered to be analogous to the claim invention because they aim to treat disease with modified viruses. Bremel teaches a peptide comprised of GWRVSE with 100% sequence identity to SEQ ID NO: 3 (reproduced above). Steinmetz teaches that the HER2 antigen can be connected to the CPMV using a linker molecule (¶0042). Steinmetz also teaches a linker group can serve to increase chemical reactivity of a substituent on either the agent or the virus particle, and thus increase the coupling efficiency, and can also improve the immunogenicity of the linked antigen (¶0042). Gupta teaches capsids were labeled with alkynes or azides at surface-exposed lysine residues using standard NHS ester chemistry followed by CuAAC to conjugate substrates such as fluorescein dyes (Section: Optimization of Reaction Conditions.).
Together, the prior art teaches that a peptide comprised of GWRVSE can be conjugated to the surface of CPMV with click-chemistry allowing specific modification and attachment of agents on the surface lysines of CPMV. Therefore, it would have been prima facie obvious before the effective filing date of the claimed invention to have conjugated a peptide comprising GWRVSE to a click-chemistry modified CPMV because doing so would allow for the delivery of active agents that are attached in a specific and reliable manner. One of ordinary skill in the art would have had a reasonable expectation of success pseudotyping a CPMV with a peptide comprising GWRSVE and using click-chemistry for further modifications given that the conjugating the peptide and using click-chemistry for further modifications is well known, has been successfully demonstrated, and commonly used in the prior art.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art at the time of filing especially in the absence of evidence to the contrary.
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Bremel and Steinmetz as applied to claims 1, 3, 4, 10, and 12 – 15 above, and further in view of Wang et al (Angewandte Chemie, 2002, 10.1002/1521-3773(20020201)41:3<459::AID-ANIE459>3.0.CO;2-O, hereinafter, “Wang”).
As discussed above, claims 1, 3, 4, 10, and 12 – 15 were rendered prima facie obvious by Bremel and Steinmetz. While the references teach the conjugating of a peptide comprising GWRSVE to a CPMV, the references fail to teach the interior modification of the CPMV by targeting cysteine side chains on the interior capsid surface.
However, regarding claim 9, Wang teaches a CPMV that can be modified through the interior cysteine residues (Figure 1). Wang teaches that thiol-selective chemical reagents were used to probe the reactivity of non-disulfide-linked cysteine residues in native CPMV (¶3). Wang teaches cysteine 295 on the interior surface of the CPMV reacts to ethyl mercury phosphate (¶3, Figure 2). Wang also teaches that fluorescein dye can be covalently attached to CYS295 (¶4, Figure 3).
Bremel, Steinmetz, and Wang are considered to be analogous to the claim invention because they aim to treat disease with modified viruses. Bremel teaches a peptide comprised of GWRVSE with 100% sequence identity to SEQ ID NO: 3 (reproduced above). Steinmetz teaches that the HER2 antigen can be connected to the CPMV using a linker molecule (¶0042). Steinmetz also teaches a linker group can serve to increase chemical reactivity of a substituent on either the agent or the virus particle, and thus increase the coupling efficiency, and can also improve the immunogenicity of the linked antigen (¶0042). Wang also teaches that fluorescein dye can be covalently attached to CYS295 (¶4, Figure 3).
Together, the prior art teaches that a peptide comprised of GWRVSE can be conjugated to the surface of CPMV and be further comprised of interior cysteine modifications. Therefore, it would have been prima facie obvious before the effective filing date of the claimed invention to have conjugated a peptide comprising GWRVSE to CPMV as well as an attached dye to CYS295 because doing so would allow for the tracing of infected cells while also allowing for further antigen presentation. One of ordinary skill in the art would have had a reasonable expectation of success pseudotyping a CPMV with a peptide comprising GWRSVE and a modified interior CYS modification given that the conjugating the peptide and modifying the inner capsid surface of CPMV is well known, has been successfully demonstrated, and commonly used in the prior art.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art at the time of filing especially in the absence of evidence to the contrary.
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Bremel and Steinmetz as applied to claims 1, 3, 4, 10, and 12 – 15 above, and further in view of Messer et al (Mol Ther, 2011, hereinafter, “Messer”) and Greene et al (US20030148932A1, hereinafter, “Greene”).
As discussed above, claims 1, 3, 4, 10, and 12 – 15 were rendered prima facie obvious by Bremel and Steinmetz. While the references teach the conjugating of a peptide comprising GWRSVE to a CPMV, the references fail to teach the conjugation of the peptide FCDGFYACYMDV (SEQ ID NO: 6) to CPMV.
However, Messer teaches the retargeting of Parvovirus B19 to HER2/neu-positive cells for breast cancer treatments (See document). Messer teaches that, “an anti-HER2/neu-binding peptidomimetic (AHNP), derived from the structure of Herceptin’s CDR-H3 loop has been developed to avoid side effects associated with whole antibody treatments and efficient HER2 interaction was demonstrated in vitro, albeit with reduced HER2 down-modulation.” Messer also teaches the replacement of the endogenous P antigen binding site of B19 with AHNP which retargeted the vector to HER2-positive tumors (See document).
Messer does not teach the sequence of AHNP.
However, Greene teaches conjugated peptides linked to detectable agents and/or cytotoxic agents (Abstract). Greene teaches that AHNP binds to HER2 and inhibits tumor growth (¶0177, 0174). Greene also teaches AHNP has a 100% sequence identity to SEQ ID NO: 6 (reproduced below).
Query Match 100.0%; Score 75; Length 13;
Best Local Similarity 100.0%;
Matches 12; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 FCDGFYACYMDV 12
||||||||||||
Db 1 FCDGFYACYMDV 12
Bremel, Steinmetz, Messer, and Greene are considered to be analogous to the claim invention because they aim to treat disease with modified viruses. Bremel teaches a peptide comprised of GWRVSE with 100% sequence identity to SEQ ID NO: 3 (reproduced above). Steinmetz teaches that the HER2 antigen can be connected to the CPMV using a linker molecule (¶0042). Steinmetz also teaches a linker group can serve to increase chemical reactivity of a substituent on either the agent or the virus particle, and thus increase the coupling efficiency, and can also improve the immunogenicity of the linked antigen (¶0042). Messer teaches the replacement of the endogenous P antigen binding site of B19 with AHNP which retargeted the vector to HER2-positive tumors (See document). Greene also teaches AHNP has a 100% sequence identity to SEQ ID NO: 6 (reproduced above).
Together, the prior art teaches that the peptide GWRVSE can be conjugated to the surface of CPMV before the addition of AHNP on the GWRVSE peptide. Therefore, it would have been prima facie obvious before the effective filing date of the claimed invention to have conjugated a peptide comprising GWRVSE to CPMV and further attach AHNP to the CMPV because doing so would allow for the targeting of HER2 expressing tumor cells. One of ordinary skill in the art would have had a reasonable expectation of success pseudotyping a CPMV with a peptide comprising GWRSVE further attached to AHNP given that the conjugating the peptide to viruses is well known, has been successfully demonstrated, and commonly used in the prior art.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art at the time of filing especially in the absence of evidence to the contrary.
Allowable Subject Matter
Claim 2 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
NO CLAIMS ARE ALLOWED
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Danyal H Alam whose telephone number is (571)272-1102. The examiner can normally be reached M - F 9am - 5pm.
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/DANYAL HASSAN ALAM/Examiner, Art Unit 1672
/THOMAS J. VISONE/Supervisory Patent Examiner, Art Unit 1672
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