Detailed Office 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 .
Status of the Claims
Acknowledgement is hereby made of receipt and entry of the communication filed 11 November, 2025. Claims 1, 2, 6-17, 19, 20, 22-25 are pending in the instant application. Applicant’s election of Group I (claims 1, 2, 6-11, 19, 20, and 22-24) without traverse is noted. Accordingly, claims 12-17 and 25 have been withdrawn from further consideration by the Examiner, pursuant to 37 C.F.R. § 1.142(b), as being drawn to a non-elected invention.
35 U.S.C. § 119
Acknowledgment is hereby made of Applicant’s claim for foreign priority based on EP 20382495.8, filed 08 June, 2021. The papers submitted under 35 U.S.C. § 119(a)-(d) have been placed of record in the file.
37 C.F.R. § 1.98
The information disclosure statement filed 23 June, 2023, has been placed in the application file and the information referred to therein has been considered.
37 C.F.R. § 1.84
The drawings (e.g., see Figs. 2B, 3A, 4, and 6) are objected to because they are illegible. Corrected drawing sheets in compliance with 37 C.F.R. § 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 C.F.R. § 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
37 C.F.R. § 1.821-1.825
37 C.F.R. § 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 C.F.R. § 1.831(b) must contain a "Sequence Listing XML", as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 C.F.R. § 1.831-1.835. This "Sequence Listing XML" part of the disclosure may be submitted:
1. In accordance with 37 C.F.R. § 1.831(a) using the symbols and format requirements of 37 C.F.R. § 1.832 through 1.834 via the USPTO’s patent electronic filing system (Patent Center) (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/patents-application-process/filing-online/legal-framework-efs-web), hereinafter "Legal Framework") in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 C.F.R. § 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 C.F.R. § 1.831(a) using the symbols and format requirements of 37 C.F.R. § 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 C.F.R. § 1.52(e)(1)(ii), labeled according to 37 C.F.R. § 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 C.F.R. § 1.52(e)(8) and 37 C.F.R. § 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
This application contains sequence disclosures (e.g., see pp. 19 and 32; Fig. 6) that are encompassed by the definitions for nucleotide and/or amino acid sequences set forth in 37 C.F.R. § 1.821(a)(1) and (a)(2). However, this application fails to comply with the requirements of 37 C.F.R. § 1.821 through 1.825 for the reason(s) set forth below. Applicants are reminded that the sequence rules embrace all unbranched nucleotide sequences with ten or more bases and all unbranched, non-D amino acid sequences with four or more amino acids, provided that there are at least 4 “specifically defined” nucleotides or amino acids. The rules apply to all sequences in a given application, whether claimed or not. All such sequences are relevant for the purposes of building a comprehensive database and properly assessing prior art. It is therefore essential that all sequences, whether only disclosed or also claimed, be included in the database. See 37 C.F.R. § 1.821(a) and M.P.E.P. § 2421.02.
With respect to sequences appearing in the specification which are not identified by sequence identifiers in accordance with 37 C.F.R. § 1.821(d), Applicant must provide the following:
- A substitute specification in compliance with 37 C.F.R. § 1.121(b)(3) and 1.125 inserting the required sequence identifiers, consisting of:
- A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
- A copy of the amended specification without markings (clean version); and
- A statement that the substitute specification contains no new matter.
The specification is objected to for failing to comply with the sequence requirements.
With respect to sequences appearing in the drawings which are not identified by sequence identifiers in accordance with 37 C.F.R. § 1.821(d). Sequence identifiers for sequences must appear either in the drawings or in the Brief Description of the Drawings. Applicant must provide:
- Replacement and annotated drawings in accordance with 37 C.F.R. § 1.121(d) inserting the required sequence identifiers; AND/OR
- A substitute specification in compliance with 37 C.F.R. § 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, consisting of:
- A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
- A copy of the amended specification without markings (clean version); and
- A statement that the substitute specification contains no new matter.
The drawings are objected to for failing to comply with the sequence requirements.
Claim Objections
Claims 1, 2, 6-11, 19, 20, and 22-24 are objected to because of the following informalities: Claim 1 references an in vitro method for detecting in at least one biological sample an antibody that binds to at least one epitope of the SARS-CoV-2 virus, comprising:
a. contacting said at least one biological sample with at least one isolated SARS-CoV-2 Mpro protein, or at least one fragment of said isolated SARS- CoV-2 Mpro protein comprising at least one epitope of the SARS-CoV-2 virus, and
b. detecting the formation of an antigen-antibody complex between said virus protein or said fragment and an antibody present in said biological sample, wherein said method is an in vitro diagnostic method for the detection of a subject having antibodies against the SARS-CoV-2 virus if an antigen-antibody complex between said virus protein, or said fragment, and an antibody present in said biological sample is detected. Line three should read “a)” and line seven should read “b)”. Appropriate correction is required.
35 U.S.C. § 112(b)
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.
Claim 22 is rejected under 35 U.S.C. § 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, regards as the invention. Two separate requirements are set forth under this statute: (1) the claims must set forth the subject matter that applicants regard as their invention; and (2) the claims must particularly point out and distinctly define the metes and bounds of the subject matter that will be protected by the patent grant.
The claim references “one or more further SARS-CoV-2 Mpro immunogens” which is confusing. Does the assay utilize additional proteases from other SARS-CoV-2 isolates? Or does the claim simply reference other SARS-CoV-2 antigens in addition to the protease? Appropriate correction is required.
Joint Inventors, Common Ownership Presumed
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 at the time any inventions covered therein were effectively filed absent any evidence to the contrary. Applicant is advised of the obligation under 37 C.F.R. § 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned at the time a later invention was effectively filed 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.
35 U.S.C. § 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 of this title, 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.
Graham v. Deere
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 U.S.P.Q. 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1, 2, 7-11, 19, 20, and 22-24 are rejected under 35 U.S.C. § 103 as being unpatentable over Amanat et al. (2020), in view of Arad (U.S. Pat. No. 11,879,893 B2, issued 23 January, 2024, and claiming priority to Prov. Appl. No. 62/972,005, filed 09 February, 2020; hereinafter referred to as “Arad (2024)”) and Wu et al. (2020a/b). The claims are directed toward an in vitro method for detecting in at least one biological sample an antibody that binds to at least one epitope of the SARS-CoV-2 virus, comprising:
a. contacting said at least one biological sample with at least one isolated SARS-CoV-2 Mpro protein, or at least one fragment of said isolated SARS-CoV-2 Mpro protein comprising at least one epitope of the SARS-CoV-2 virus; and,
b. detecting the formation of an antigen-antibody complex between said virus protein or said fragment and an antibody present in said biological sample,
wherein said method is an in vitro diagnostic method for the detection of a subject having antibodies against the SARS-CoV-2 virus, wherein said subject is diagnosed as having antibodies against the SARS-CoV-2 virus if an antigen-antibody complex between said virus protein, or said fragment, and an antibody present in said biological sample is detected (claim 1). Claim 2 specifies the assay is capable of detecting IgA, IgG, and IgM. Claims 6-8 and 11 reference specific SARS-CoV-2 Mpro proteins or fragments thereof. Claim 9 specifies the protein of interest is recombinant. Claim 10 references a biological sample comprising blood, plasma, or serum. Claims 19 and 20 reference ELISA immunoassay formats. Claims 22-24 further specify that additional SARS-CoV-2 antigens (e.g., S) are included in the assay.
Amanat et al. (2020) disclose a serological enzyme-linked immunosorbent assay for the screening and identification of human
SARS-CoV-2 seroconverters. The assay can be adjusted to detect different antibody types in serum and plasma. The authors utilized two different recombinant forms of the spike (S) protein from the SARS-CoV-2 Wuhan-Hu-1 isolate. This is the same isolate employed in the instant application and corresponds to SEQ ID NO.: 1. Various modifications were made to the S proteins including the addition of a His tag. ELISA assays were performed on human serum samples. Detailed methods for the production of recombinant proteins, the processing of human plasma and serum samples, and ELISA formats were provided (see Methods, Recombinant proteins, Human samples, and ELISA, respectively, on p. 1037). This teaching does not disclose the utilization of SARS-CoV-2 Mpro (particularly corresponding to SEQ ID NO.: 1, the Wuhan-Hu-1 isolate) in an ELISA assay.
Arad (2024) discloses a SARS-CoV-2 Mpro protease cleavage assay to detect Mpro in a sample. Two different forms of 3CLPro were produced and utilized in the assay. These two proteases display >95% amino acid sequence identity with SEQ ID NO.: 1 (see SEQ ID NOS.: 34 and 35 in the patent and Appendix A in the Office action). This teaching does not disclose the utilization of Mpro in an immunoassay.
Wu et al. (2020a/b) disclose the isolation and characterization of a novel SARS-CoV-2 isolate, designated Wuhan-Hu-1 or 2019-nCoV. The Mpro in this isolate is identical to that set forth in SEQ ID NO.: 1 of the instant application. This teaching also does not disclose the utilization of Mpro in an immunoassay.
However, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to prepare recombinant 3CLPro proteins from the SARS-CoV-2 isolates of Arad (2024) and Wu et al. (2020a/b), and to utilize these antigens in the ELISA assay of Amanat et al. (2020), to detect SARS-CoV-2-specific antibodies. One of ordinary skill in the art would have also been motivated to employ multiple SARS-CoV-2 antigens (e.g., S and Mpro) in the ELISA format of Amanat et al. (2020) to increase the chance of detecting anti-SARS-CoV-2 antibodies.
Correspondence
Any inquiry concerning this communication should be directed to Jeffrey S. Parkin, Ph.D., whose telephone number is (571) 272-0908. The Examiner can normally be reached Monday through Friday from 10:00 AM to 6:00 PM. A message may be left on the Examiner's voice mail service. 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 are unsuccessful, the Examiner's supervisor, Michael Allen, Ph.D., can be reached at (571) 270-3497. Direct general status inquiries to the Technology Center 1600 receptionist at (571) 272-1600.
Information regarding the status of an application may be obtained from the Patent Center. Status information for published applications may be obtained from the Patent Center. Status information for unpublished applications is available through the Patent Center for authorized users only. Should you have questions about access to Patent Center, 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.
Respectfully,
/JEFFREY S PARKIN/Primary Examiner, Art Unit 1671 07 January, 2026
Appendix A
RESULT 11
US-17-883-833-35
Sequence 35, US/17883833
Patent No. 11879893
GENERAL INFORMATION
APPLICANT: NLC PHARMA LTD (en)
TITLE OF INVENTION: RAPID DETECTION TEST FOR SARS-COV-2 (en)
CURRENT APPLICATION NUMBER: US/17/883,833
CURRENT FILING DATE: 2022-08-09
NUMBER OF SEQ ID NOS: 39
SEQ ID NO 35
LENGTH: 320
TYPE: PRT
NAME/KEY: REGION
LOCATION: 1..320
QUALIFIERS: note = 3CL protease of the SARS-CoV-2 virus with the histidine tag and cleavable sequence
FEATURE:
NAME/KEY: source
OCATION: 1..320
QUALIFIERS: mol_type = protein organism = synthetic construct
Query Match 95.5%; Score 1646; Length 320; Best Local Similarity 100.0%; Matches 306; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 6 SGFRKMAFPSGKVEGCMVQVTCGTTTLNGLWLDDVVYCPRHVICTSEDMLNPNYEDLLIR 65
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 15 SGFRKMAFPSGKVEGCMVQVTCGTTTLNGLWLDDVVYCPRHVICTSEDMLNPNYEDLLIR 74
Qy 66 KSNHNFLVQAGNVQLRVIGHSMQNCVLKLKVDTANPKTPKYKFVRIQPGQTFSVLACYNG 125
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 75 KSNHNFLVQAGNVQLRVIGHSMQNCVLKLKVDTANPKTPKYKFVRIQPGQTFSVLACYNG 134
Qy 126 SPSGVYQCAMRPNFTIKGSFLNGSCGSVGFNIDYDCVSFCYMHHMELPTGVHAGTDLEGN 185
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 135 SPSGVYQCAMRPNFTIKGSFLNGSCGSVGFNIDYDCVSFCYMHHMELPTGVHAGTDLEGN 194
Qy 186 FYGPFVDRQTAQAAGTDTTITVNVLAWLYAAVINGDRWFLNRFTTTLNDFNLVAMKYNYE 245
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 195 FYGPFVDRQTAQAAGTDTTITVNVLAWLYAAVINGDRWFLNRFTTTLNDFNLVAMKYNYE 254
Qy 246 PLTQDHVDILGPLSAQTGIAVLDMCASLKELLQNGMNGRTILGSALLEDEFTPFDVVRQC 305
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 255 PLTQDHVDILGPLSAQTGIAVLDMCASLKELLQNGMNGRTILGSALLEDEFTPFDVVRQC 314
Qy 306 SGVTFQ 311
||||||
Db 315 SGVTFQ 320