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 .
Response to Amendment
The Amendment filed 11/04/2025 in which claims 1 and 6 were amended and claims 2 and 3 were canceled, has been entered. Claims 7 – 20 were previously withdrawn.
Claims 1 and 4 - 6 are under examination on the merits.
Priority
(Previous objection, withdrawn) Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Nucleotide and/or Amino Acid Sequence Disclosures
(Previous objection, withdrawn) Applicant’s substitute specification and sequence listing submitted on 11/04/2025 have overcome the objection previously set forth in the Non-Final Office Action mailed 08/04/2025.
Claim Objections
(Previous objection, withdrawn as to claims 3 and 6).
Applicant has cancelled claim 3.
Applicant’s amendment to claim 6 has overcome previous objections to that claim.
Claim Rejections - 35 USC § 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.
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.
(Previous rejection, withdrawn as to claims 1-6) Claims 1 – 6 were rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to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.
Applicant has cancelled claims 2 and 3.
Applicant’s amendment to claim 1 and 6 has overcome previous rejections to that claim.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
(Previous rejection, withdrawn as to claim 1). Claim 1 was rejected for containing subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Applicant’s amendment to claim 1 has overcome previous rejections to that claim.
Claim Rejections - 35 USC § 101
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.
(Previous rejection, maintained and modified as to claim 1 in view of the amendment, withdrawn as to now canceled claim 2 and 3).
Claim 1 is rejected under 35 U.S.C. 101 because the claimed inventions are directed to a judicial exception without significantly more. This judicial exception is not integrated into a practical application, and the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception for the reasons set forth below. See MPEP § 2106 for patent subject matter eligibility analysis.
Claim 1 is drawn to an anti-SARS-CoV-2-infection protein which is a composition of matter and a statutory category of invention (Step 1- YES).
Claim 1 is drawn to an anti-SARS-CoV-2-infection protein comprising a domain that binds with an ACE2 receptor as contained in a SARS-CoV-2 S protein comprising the amino acid sequence of SEQ ID NO: 3.
Thus, claim 1 is drawn to any protein with a domain that binds to ACE2, such as the SARS-CoV-2 spike RBD, which is a domain of the naturally occurring viral spike protein. A domain of a naturally occurring protein does not exhibit a markedly different characteristic from the naturally occurring protein. SEQ ID NOs: 3 is 100% identical to the naturally occurring SARS-CoV-2 sequence taught by Zhang (prior art of record) (GenBank Accession number MN908947.1) (see alignments below). As such, claim 1 recites a judicial exception in the form of a natural phenomenon (product of nature) (Step 2A, Prong 1- YES).
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The crux of the claimed inventions is a protein comprising a domain that binds to ACE2. The instant claims do not recite any additional elements that integrate this judicial exception into a practical application, such as specific treatment or prophylaxis. Rather, the instant claims are limited to the judicial expectation. As such, the instant claims do not recite additional elements that integrate the judicial exception into a practical application (Step 2A, Prong 2- NO).
As detailed above and in the 35 U.S.C. § 103 rejections below, the claimed polypeptides of SEQ ID NOs: 3 is a naturally occurring viral polypeptide. The instant claims do not recite any additional elements that amount to significantly more than the judicial exception (Step 2B- NO).
Accordingly, claim 1 does not constitute patent eligible subject matter under 35 U.S.C. § 101.
Applicant has cancelled claims 2 and 3.
Claim Rejections - 35 USC § 102
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.
(Previous objection, withdrawn as to claim 1). Claim 1 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lan (prior art of record).
Claim 1 was rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lan. Applicant’s amendment to claim 1 has overcome previous objections to that claim.
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.
(Previous objection, withdrawn as to now canceled claims 2 and 3) Claims 2 and 3 were rejected under 35 U.S.C. 103 as being unpatentable over Lan as applied to claim 1 above and further in combination with Zhang.
Applicant has cancelled claims 2 and 3.
(Previous rejection, maintained and modified as to claim 1 in view of the amendment) Claim 1 is rejected under 35 U.S.C. 103 as being unpatentable over Lan in view of Zhang.
Lan teaches the RBD domain of SARS-CoV-2 S protein binds to the ACE2 receptor (Abstract and Figure 1). This reference does not teach that the amino acid sequence of the RBD domain is SEQ ID NO: 3 or SEQ ID NO: 4.
[AltContent: textbox ([img-media_image2.png]SEQ ID NO:3 alignment)]However, Zhang teaches the SARS-CoV-2 genomic and coding sequences. Alignment of SEQ ID NOs: 3 and a with the SARS-CoV-2 S protein sequence taught by Zhang indicates that the claimed sequences are 100% identical to a portion of the SARS-CoV-2 S protein taught by Zhang (reproduced below, Sequence 2 is SEQ ID NO:3 or SEQ ID NO:4, Sequence 1 is Zhang).
[AltContent: textbox ([img-media_image3.png]SEQ ID NO:4 alignment)]
It would have been prima facie obvious to a person with ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Lan and Zhang to arrive at an anti-viral SARS-CoV-2 RBD protein with the sequence of SEQ ID NOs: 3 or 4. One would have been motivated to do so for the advantage of using a clinically relevant viral protein domain. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Thus, the inventions of claim 1 as a whole were prima facie obvious to one of ordinary skill in the art before the effective filing date of the invention, especially in the absence of evidence to the contrary.
(Previous rejection, maintained and modified as to claims 4-6 in view of the amendment) Claims 4-6 are rejected under 35 U.S.C. 103 as being unpatentable over Lan and Zhang as applied to claim 1 above and further in combination with Liu (prior art of record).
As discussed above, claim 1 was rendered prima facie obvious by the teachings of Lan and Zhang. The references do not teach that a precursor of the protein of claim 1 is linked to a signal peptide and/or protein tag (i.e., claim 4), a protease recognition sequence for protein tag removal (i.e., claim 5), or that the sequence of the domain of the precursor protein is SEQ ID NO: 5 (i.e., claim 6).
However, Liu teaches recombinant protein production in a baculovirus system (title). Specifically, Liu teaches that the baculovirus system can be used to produce recombinant viral proteins (e.g., influenza polymerase, slide 18) and teaches use of protein tags (e.g., His tags), signal peptides (e.g., Gp67), and protease recognition sequences (e.g., TEV) as part of the recombinant protein expression strategy (slide 15). Although Liu does not expressly teach SEQ ID NO: 5, the examiner notes that SEQ ID NO: 5 is the Gp67 signal peptide followed by the S protein RBD followed by a His tag (spec page 4 line 3).
It would have been prima facie obvious to a person with ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Lan, Zhang, and Liu to arrive at a precursor of the anti-viral RBD protein comprising a protein tag and/or signal peptide and a protease recognition sequence, such as the sequence recited by SEQ ID NO: 5. One would have been motivated to do so for the advantage of efficiently producing secreted recombinant protein as taught by Liu (slides 3 and 15). There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Thus, the inventions of claims 4-6 as a whole were prima facie obvious to one of ordinary skill in the art before the effective filing date of the invention, especially in the absence of evidence to the contrary.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
(Previous rejection, maintained and modified as to claims 1 and 4- 6 in view of the amendment) Claims 1 and 4-6 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 5-6 of copending Application No. 19147928.
Instant claim 1 is drawn to an anti-SARS-CoV-2-infection protein comprising a domain from the SARS-CoV-2 S protein, wherein the domain binds with an ACE2 receptor, which reads on the receptor binding domain (RBD) of the SARS-CoV-2 S protein. Copending application ‘928 claim 1 is drawn to a protein against infection by a SARS-CoV-2 Omicron variant comprising a sequence at least 98% identical to SEQ ID NOs: 1-6. As detailed in the 35 USC 102 rejection above, the limitation “anti-SARS-CoV-2-infection protein” and “a protein against infection” are intended uses of the protein and do not limit the claims. Thus, both instant claim 1 and copending application ‘928 claim 1 are drawn to SARS-CoV-2 proteins.
Alignment of instant SEQ ID NO: 3 and copending application ‘928 SEQ ID NO: 1 reveals 91% identity as both sequences are drawn to a SARS-CoV-2 S protein RBD (see alignment below). Therefore, because instant claim 1 is drawn to a SARS-CoV-2 RBD, it is not patentably distinct from copending application ‘928 claim 1.
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Instant claims 4-6 are drawn to a precursor of the protein of claim 1 that comprises a signal peptide and/or protein tag and a protease recognition sequence. These limitations are comprised in SEQ ID NO: 5. Copending application ‘928 claim 5 is drawn to a precursor protein comprising a signal peptide and/or protein tag and claim 6 is drawn to the precursor protein comprising a protease recognition sequence. Thus, instant claims 4-6 are not patentably distinct from copending application ‘928 claims 5-6 in view of Wu et al and Dai et al.
(Previous rejection, withdrawn as to now canceled claims 2 and 3) Applicant has cancelled claims 2 and 3.
Response to Arguments
Applicant's arguments filed 11/04/2025 have been fully considered but they are not persuasive.
Applicant contends on page 7 of the Remarks: 35 U.S.C. § 101 rejection: Applicant states “1. Markedly Different Characteristics
The claimed anti-SARS-CoV-2-infection protein comprises a domain from the SARS- CoV-2 S protein that binds to ACE2 and has a specific amino acid sequence of SEQ ID NO: 3 or SEQ ID NO: 4. These sequences are not mere fragments of naturally occurring proteins but are engineered constructs with enhanced immunogenicity and stability, as demonstrated in the specification.
SEQ ID NO:3 includes four additional amino acids (NFNG) beyond the canonical RBD (319-541), which are shown to improve protein folding and dimerization via disulfide bonding, thereby enhancing immune response. SEQ ID NO:4 is a variant lacking the N-terminal R residue, which also exhibits distinct immunological properties. These modifications result in markedly different characteristics compared to the naturally occurring spike protein domain.
2. Integration into a Practical Application
The claimed protein is not merely a product of nature but is effective for integrating into a specific therapeutic application - namely, as an active component of a vaccine or drug for SARS- CoV-2 infection prevention or treatment. The specification provides experimental data showing that the protein induces a robust antibody response and blocks ACE2 binding, demonstrating a real-world utility beyond the natural phenomenon.
3. Significantly More Than the Judicial Exception
The claims recite additional elements that amount to "significantly more" than the judicial exception. The modified protein sequences here are used in a manner that provides unexpected and superior immunological effects, as supported by comparative data in the specification.
These features transform the claimed invention into a practical and inventive application of a natural phenomenon, satisfying Step 2B of the USPTO's eligibility framework.”
In response: The newly amended claim does not overcome the 35 U.S.C. § 101 rejection.
In response, the claimed anti-SARS-CoV-2-infection protein comprises a domain from the SARS- CoV-2 S protein that binds to ACE2 and has a specific amino acid sequence of SEQ ID NO:3 or SEQ ID NO:4. SEQ ID NO:3 or SEQ ID NO:4 are fragments of naturally occurring proteins comprised of identical sequences as the naturally found wild type sequence (see above and see also below). Zhang, which was discussed in the previous office action, teaches the amino acid sequence “NFNG” is a naturally occurring sequences in the spike protein of SARS-CoV-2. Additionally, “NFNG” is a natural variant that is not beyond the canonical RBD as evidenced by Dorlass et al (NCBI, Direct Submission, 2021, here in after “Dorlass”) and Klaif (NCBI, Direct Submission, 2021, hereinafter, “Klaif”). Dorlass evidences the sequence of SARS-CoV-2 spike protein naturally found in subjects from Brazil with a SARS-CoV-2 infection (reproduced below). Klaif evidences the sequence of SARS-CoV-2 spike protein naturally found in subjects from Iraq with a SARS-CoV-2 infection (reproduced below). Importantly, both Dorlass and Klaif show the NFNG amino acid sequence is a natural sequence found in the SARS-CoV-2 spike protein. Any property arising from the amino acid sequence “NFNG” would be inherent to the natural protein. As written the claims are not [AltContent: textbox ([img-media_image5.png]
Klaif)]integrated into a specific therapeutic application. As such, the claim is not “significantly more”
[AltContent: textbox ([img-media_image6.png]
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Applicant contends on page 8 of the Remarks: 35 U.S.C. § 102 rejection: Applicant states “Lan does not teach that the amino acid sequence of the anti- viral domain is SEQ ID NO:3. SEQ ID NO:4 is identical to SEQ ID NO:3 but lacks the N-terminal R. Thus, Lan does not teach that the amino acid sequence of the anti-viral domain is SEQ ID NO:3 or SEQ ID NO:4.
In response: The newly amended claim 1 does overcome the 35 U.S.C. § 102 rejection.
Applicant contends on page 9 of the Remarks: 35 U.S.C. § 103 rejection: Applicant states that claims 2 and 3 have been cancelled.
In response: The 35 U.S.C. § 103 rejection to claims 2 and 3 has been withdrawn.
Applicant contends on page 15 of the Remarks: 35 U.S.C. § 103 rejection: Applicant states “Lan fails to teach or suggest the claimed invention for at least the reasons discussed above.
Liu teaches general strategies for recombinant protein expression, including the use of signal peptides, tags, and protease recognition sites. However, Liu does not disclose or suggest the specific precursor protein constructs claimed here, particularly SEQ ID NO:5, which includes a Gp67 signal peptide, the RBD domain, and a His tag.
The combination of these elements in the claimed sequence is not a routine or obvious design choice. The specification demonstrates that this construct enables efficient expression, purification, and immunogenicity of the RBD protein, which is not taught or suggested by Liu or Lan taken alone or together.”
In response: As discussed above and previously, adding a Gp67 signal peptide and a His tag to a protein is routine in the art. Furthermore, as discussed above and previously, one would have been motivated to engineer a section of the RBD such as SEQ ID NO:3 or SEQ ID NO:4 for the advantage of efficiently producing secreted recombinant protein as taught by Liu (slides 3 and 15).
Applicant contends on page 16 of the Remarks: Double Patent: Applicant argues that the provisional nature of the rejection, Applicant reserves the right to respond to the provisional rejection at a later date, upon resolution of other issues presented in this Official Action, other Official Actions, and/or other related patent applications.
In response: Applicant’s arguments have been full considered but they are not persuasive. Applicant requests that the rejection be held in abeyance until allowable subject matter is identified. This has been fully considered but is not found to be persuasive. Applicant’s attention is respectfully directed to M.P.E.P. § 804(I)(B)(1), which states:A complete response to a nonstatutory double patenting (NSDP) rejection is either a reply by applicant showing that the claims subject to the rejection are patentably distinct from the reference claims or the filing of a terminal disclaimer in accordance with 37 CFR 1.321 in the pending application(s) with a reply to the Office action (see MPEP § 1490 for a discussion of terminal disclaimers). Such a response is required even when the nonstatutory double patenting rejection is provisional.
As filing a terminal disclaimer, or filing a showing that the claims subject to the rejection are patentably distinct from the reference application’s claims, is necessary for further consideration of the rejection of the claims, such a filing should not be held in abeyance. Only objections or requirements as to form not necessary for further consideration of the claims may be held in abeyance until allowable subject matter is indicated. Replies with an omission should be treated as provided in MPEP § 714.03.Therefore, an application must not be allowed unless the required compliant terminal disclaimer(s) is/are filed and/or the withdrawal of the nonstatutory double patenting rejection(s) is made of record by the examiner. See MPEP § 804.02, subsection VI, for filing terminal disclaimers required to overcome nonstatutory double patenting rejections in applications filed on or after June 8, 1995. (emphasis added)
Accordingly, the rejection is expressly not held in abeyance.
Conclusion
NO CLAIMS ARE ALLOWED
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 Danyal H Alam whose telephone number is (571)272-1102. The examiner can normally be reached M - F 9am - 5pm.
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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.
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/DANYAL HASSAN ALAM/Examiner, Art Unit 1672
/THOMAS J. VISONE/Supervisory Patent Examiner, Art Unit 1672
