DETAILED ACTION
Final Rejection
Notice of Pre-AIA or AIA Status
1. 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
2. Applicant’s election without traverse of Group I claims 1, 6-8, 10-21, and 23-26, and a species of the antibody DH1047 (SEQ ID NO: 1125, and SEQ ID NO: 1127) in the reply filed on 01/20/2026 is acknowledged.
Examiner’s Note:
Elected antibody species SEQ ID NO: 1125, and SEQ ID NO: 1127 (DH1047) is free of prior art due to amended claim limitation for requirement of VH and VL 100% amino acid identity.
A prior art search was extended to additional species of antibodies to Group I claims 1, 6-7, 14 that recited SEQ ID NOs for VH and VL or CDRs of the antibodies (a genus of antibody) to comprise 100% amino acid sequence identity.
Status of Claims
3. Claims 1-12, 14-17, and 20-26 as filed in claim listing on 06/24/2026 are pending.
4. Claims 2-5, 9, and 22 are withdrawn from examination as being directed to the non-elected invention.
5. Claims 13, and 18-19 are cancelled by the applicant as per filing on 06/24/2026.
6. Claims 1, 6-8, 10-12, 14-17, 20-21, and 23-26 are under examination in this office action.
Priority
7. This application claims the benefit of and priority to US Patent Application No.
63/078,666 filed on September 15, 2020, US Patent Application No. 63/126,267 filed on December 16, 2020, US Patent Application No. 63/180,564 filed on April 27, 2021, and US Patent Application No. 63/212,078 filed on June 17, 2021.
Information Disclosure Statement
8. The two-information disclosure statement (IDS) submitted on 03/15/2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Objection to Specification (maintained)
9. The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
See, instant specification pages 100-106, 117-119, 131-134, 152-156.
10. The lengthy specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Withdrawn Objection to Specification
11. Withdrawn objection to the specification because the applicant has amended the specification (06/24/2026) to delete embedded hyperlink and/or other form of browser-executable code. http:// or other browser-executable code.
Withdrawn Claim Objections
12. Withdrawn objection to the Claim 1 (and dependent elected Group I claims) in view of applicant’s amendment (06/24/2026) of claim 1 in response to objection.
Withdrawn Claim Rejections - 35 USC § 112
13. Withdrawn rejection of claims 1, 6-8, 10-21, and 23-26 under 35 U.S.C. 112(b) in view of the applicant’s amendment (06/24/2026) to the claims.
Withdrawn Claim Rejections - 35 USC § 112
14. Withdrawn written description rejection of claims 1, 6-8, 10-21, and 23-26 under 35 U.S.C. 112(a) in view of the applicant’s amendment (06/24/2026) to the claims.
Withdrawn Claim Rejections - 35 USC § 112
15. Withdrawn enablement requirement rejection of claims 24-26 under 35 U.S.C. 112(a) in view of the applicant’s amendment (06/24/2026) to the claims.
Withdrawn Claim Rejections - 35 USC § 103
16. Withdrawn rejection of claims under 35 U.S.C. 103 in view of amendment to the instant claim 1 (elected dependent claims inherits instant claim 1 limitations) to comprise 100% amino acid sequence identity to the claimed VH and VL domains of the antibody or monoclonal antibody.
Claim Interpretation (modified)
17. The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art.
Claim 1: The instant claim 1 is interpreted to be directed to a pharmaceutical composition comprising a recombinant coronavirus monoclonal antibody, or an antigen binding fragment thereof, which binds to coronavirus spike protein and comprises a variable heavy (VH) domain and a variable light (VL) domain that have amino acid sequences that have 100% sequence identity to the VH and VL domains of an antibody selected from the group consisting of DH1041 (SEQ ID NOS: 1101, 1103), DH1042 (SEQ IDNOS: 1105,1107), DH1043 (SEQ IDNOS: 1109,1111), ……………… or DH1159.2 (SEQ ID NOS: 1266, 1268) or
wherein the VH domain and VL domain each have 100% sequence identity to the VH and VL domains, respectively, of an antibody selected from the group consisting of: DH1041 (SEQ ID NOS: 1101, 1103), DH1042(SEQ ID NOS: 1105, 1107), DH1043(SEQ ID NOS:1109,1111), ……………………. or DH1159.2 (SEQ ID NOS: 1266, 1268).
The claimed monoclonal antibodies were recombinantly derived from a single B cell of a coronavirus infected individual (human), and or a B cell of a coronavirus infection recovered individual (See, instant specification para [0013], [0062]). In certain embodiments the monoclonal antibodies are produced by a clone of B-lymphocytes (See, instant specification para [0198], [0273]), and thus the antibody is also interpreted as a monoclonal antibody produced by single clone of plasma cell or B-lymphocytes. The monoclonal antibody is also interpreted to comprise wild type HV and VL sequence without amino acid substitution to generate a recombinant monoclonal antibody.
According to instant specification, the pharmaceutical composition does not alter critical structure of claimed antibody VH and VL.
Claims 6-7: The instant claims 6 and 7 are interpreted to an antibody with and heavy and light chain each comprising three CDR H1-H3 and CDR L-L3 for heavy and light chain respectively with specific recited SEQ ID NOs sequences paired to form a functional antibody having at least at least 100% sequence identity.
Claims 8-9, and 21: The claims 8-9, and 21 comprise antibodies that bind to RBD domain of a coronavirus. Claim 8 additionally comprise antibody that binds to coronavirus domain NTD, or S2.
Claims 24 and 26: A method of treating a coronavirus infection in a subject in need thereof, comprising administering the recombinant antibody of claim 1 in an amount suitable to effect treatment of coronavirus infection.
The claim 26 is interpreted directed to a method of treating coronavirus infection comprising administering therapeutic amount of the pharmaceutical composition of claim 20 to a subject.
Claim Rejections - 35 USC § 101 (modified)
18. 35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1, 6-8, 10-12, 14-17, 20-21 and 23 are rejected under 35 U.S.C. 101 because according to the broadest reasonable interpretation (BRI) in view of the instant specification, the claim 1 (and dependent claims 6-8, 10-12, 14-17, 20-21 and 23) are interpreted to be directed to a product of nature, an antibody, a monoclonal antibody, a recombinant monoclonal antibody that is recombinantly derived from a single B cell of a coronavirus infected individual (human), and or a B cell of a coronavirus infection recovered individual (See, instant specification para [0013], [0062]).
The amended claim comprises “A pharmaceutical composition, inter alia, anti-coronavirus antibody, a monoclonal antibody, a recombinant monoclonal antibody (see, claim 1). A pharmaceutical composition comprises a pharmaceutically acceptable excipient, diluent or carrier making the composition of claim 1 suitable for pharmaceutical use (see, claim 1). The specification para [0019], [0026], ) recites “In certain aspects, the invention provides a pharmaceutical composition comprising the recombinant antibodies of the invention”. The composition is suitable for pharmaceutical use (para [0053]). The pharmaceutical composition comprises at least one antibody of the invention formulated as a recombinant protein (see, para [0031]). In certain aspect, the composition further comprises a pharmaceutically acceptable excipient, diluent or carrier (see, para [0054]). The limitations “A pharmaceutical composition, and a pharmaceutically acceptable carrier or diluent” does not significantly modify the claimed product of nature (e.g. claimed antibody) for structure of the claimed antibody or a monoclonal antibody, a recombinant monoclonal antibody. The limitations “A pharmaceutical composition, and a pharmaceutically acceptable carrier or diluent” are directed to intended use without significantly modifying the claimed product of nature (e.g. claimed antibody) for structure of the claimed antibody.
In certain embodiments the monoclonal antibodies are produced by a clone of B-lymphocytes (See, instant specification para [0198], [0273]), and thus the antibody is also interpreted as a monoclonal antibody produced by single clone of plasma cell or B-lymphocytes. The monoclonal antibody is also interpreted to comprise wild type HV and VL sequence without amino acid substitution to generate a recombinant monoclonal antibody (See, instant specification para [0273). B cell clones or transfected host-cells of the invention can be used in various ways e.g., as a source of monoclonal antibodies, as a source of nucleic acid (DNA or mRNA) encoding a monoclonal antibody of interest, for research, etc (See, instant specification para [0282]).
Step 1: According to MPEP § 2106, the claimed invention must be to one of the four statutory categories. According to 35 U.S.C. 101 the eligibility test, the claim 1 (and dependent claims 6-8, 10, and 14) are directed to a statutory category, e.g. composition of matter (the claimed recombinant monoclonal antibody with a function of binding to a coronavirus spike protein), therefore, statutory category eligibility, Step 1: Yes.
Step 2: As described in the instant specification and the prior art Cao et al 2020, Zost et al 2020, and Liu et al 2020 recited below the claimed the claimed genus of recombinant monoclonal antibody or monoclonal antibody is produced by a human single B cell (plasma cell) in response to a coronavirus infection and can be termed as a monoclonal antibody which naturally comprise the antigen binding fragment, Fc, VH and VL chains. The antibody has a function of binding to spike protein (surface protein of a coronavirus) and or neutralizing a coronavirus. The claimed recombinant monoclonal antibodies uses the VL and VL sequences from the B cell and does not have markedly different characteristics or function from what exist in nature or human, and thus is “a product of nature” exception, Step 2A: Prong 1- Yes :claim 1 (and dependent claims) recite a “judicial exception” a product of nature.
The claim 1 (and dependent claims 6-8, 10-12, 14-17, 20-21 and 23) fails to integrate (e.g. composition of matter-the claimed recombinant monoclonal antibody with a function of binding to a coronavirus spike protein) the judicial exception into a practical application (e.g method of treatment, diagnostic assay or purification) or contain additional elements that result in a “markedly different” antibody as compared to the natural conunterpart, Step 2A: Prong 2-No.
The claim 1 (and dependent claims 6-8, 10-12, 14-17, 20-21 and 23) does/do not include additional elements that are sufficient to amount to significantly more to the claimed composition of matter recombinant monoclonal antibody (a genus) (than the judicial exception because the claims recite recombinant monoclonal antibody and additional antibody species in the genus, as to constitute an “inventive concept” (e.g. improvement) Step 2B: No.
Cao et al 2020 teaches a neutralizing (SARS CoV-2 spike RBD domain binding) and non-neutralizing monoclonal antibody obtained from a single B cell or plasma cell, by using recombinant DNA technology tools and methods, of an individual that was known to be infection with SARS-CoV-2 virus (See, abstract, entire article).
Zost et al 2020 teaches potent neutralizing mAbs recognizing non-overlapping sites, COV2-2196 and COV2-2130 (RBD binding or ACE2 blocking), bound simultaneously to S and synergistically neutralized authentic SARS-CoV-2 virus. A large panel of SARS-CoV-2 S protein-reactive mAbs from the B cells of two convalescing individuals who had been infected with SARS-CoV-2 in Wuhan China. The antibodies were isolated using diverse tools for isolation and cloning of single antigen-specific B cells and the antibody variable genes encoding monoclonal antibodies. The Mabs were potently neutralizing and protective human antibodies against SARS-CoV-2. The Mabs were specific for RBD, S2 and ACE2 blocking neutralizing function (See, abstract, Figure 1-2, section on Antibodies, entire article).
Liu et al 2020 teaches potent neutralizing monoclonal antibodies (recombinantly obtained using recombinant DNA technology and methods) against multiple epitopes on SARS-CoV-2 spike. Isolation of sixty-one SARS-CoV-2-neutralizing monoclonal antibodies from B cells of five patients infected with SARS-CoV-2 and admitted to hospital with severe coronavirus disease 2019 (COVID-19). Among these are nineteen antibodies that potently neutralized authentic SARS-CoV-2 in vitro, nine of which exhibited very high potency, with 50% virus-inhibitory concentrations of 0.7 to 9 ng ml−1. Epitope mapping showed that this collection of nineteen antibodies was about equally divided between those directed against the receptor-binding domain (RBD) and those directed against the N-terminal domain (NTD), indicating that both of these regions at the top of the viral spike are immunogenic. In addition, two other powerful neutralizing antibodies recognized quaternary epitopes that overlap with the domains at the top of the spike. Cryo-electron microscopy reconstructions of one antibody that targets the RBD, a second that targets the NTD, and a third that bridges two separate RBDs showed that the antibodies recognize the closed, ‘all RBD-down’ conformation of the spike. Several of these monoclonal antibodies are promising candidates for clinical development as potential therapeutic and/or prophylactic agents against SARS-CoV-2 (See, abstract, Fig 1-4, page 451 col 1 section on Isolation and construction of mAbs).
Thus, claims 1, 6-8, 10-12, 14-17, 20-21 and 23 are rejected under 35 U.S.C. 101 as the claimed monoclonal antibody is a product of nature and the limitations “A pharmaceutical composition, and a pharmaceutically acceptable carrier or diluent” does not significantly modify the claimed product of nature (e.g. claimed antibody) for structure of the claimed antibody or a monoclonal antibody, a recombinant monoclonal antibody. The claimed monoclonal antibody is a product of nature without modification of the sequence and the claims are directed to a genus of monoclonal antibody that encompass entire B cell repertoire of VH and VL chain sequence comprising monoclonal antibodies from a coronavirus infected individual B cell or plasma cells as recited supra, and because the claimed composition does not include any additional features that modify the structure of the claimed antibody and that could add significantly more to the exception.
Allowable Subject Matter
19. Claims 24-26 are objected to as being dependent upon a rejected base claim 1, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
20. The recombinant monoclonal antibody variable heavy (VH) domain and a variable light (VL) chain amino acid sequence that requires 100% amino acid identity to binds to a coronavirus spike protein as per SEQ ID NOs recited in elected instant claims 1, 6-7 and 14 are free of prior art.
Response to Arguments
21. Applicant’s arguments filed on 06/24/2026 with respect to the rejected claim(s) in the Non-Final rejection office action mailed on 03/24/2026 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
22. Relevant Prior Art:
Liao et al 2009. High-throughput isolation of immunoglobulin genes from single human
B cells and expressions as monoclonal antibodies. Journal of Virological Methods, 158 (2009) 171–179).
Kyratsous et al 2019 (US20190351049A1, 11/21/2019). Human Antibodies to Middle East Respiratory Syndrome - Coronavirus Spike Protein. Cited in incoming PCT opinion. The US20190351049A1 discloses antibody that has <90% sequence identity to the elected or claimed antibody species in the genus. Applicants have amended the claims in response to lack of unity of invention office action.
Pereira et al 2011 (US20090136510A1, 05/28/2009). Inhibition of macrophage-stimulating protein receptor (RON) and methods of treatment thereof. Cited in incoming PCT opinion.
Lightwood et al 2020 (WO2020148554A1, 07/23/2020). Antibodies to ebola virus glycoprotein. Cited in incoming PCT opinion.
Lou et al. 2020. Cross-neutralization antibodies against SARS-cOv-2 and RBD mutations from convalescent patient antibody libraries. bioRxiv 2020.06.06. 137513.
Conclusion
23. No claim is allowed.
24. 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). Applicants are reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
25. 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 SAMADHAN J JADHAO whose telephone number is (703)756-1223. The examiner can normally be reached M-F 8:00-5:00.
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, Thomas J Visone can be reached at 571-270-0684. 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.
/SAMADHAN JAISING JADHAO/Examiner, Art Unit 1672
/BENNETT M CELSA/Primary Examiner, Art Unit 1600
