DETAILED ACTION
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-20, 27, 28 and 31-47, and the species of a set of 15 oligopeptides (SEQ ID NO: 22-36) in the reply filed on June 4, 2026 is acknowledged. According to the elected species, claims 5, 27, 31-43 and 45 are under examination.
Claims Summary
Claims 5 and 45
Claims 5 and 45 (elected species) are directed to a composition comprising a set of 15 isolated oligopeptides comprising SEQ ID NO: 22-36, or one or more variants thereof having at least 80% sequence identity thereto, each comprising a SARS-CoV-2 S protein RBD CD4+ T-cell epitope. The intended uses for the composition are:
Diagnosis of COVID-19
Prognosis of COVID-19
Detecting an antigen-specific T-cell mediated immune response to SARS-CoV-2
The sequences of SEQ ID NO: 22-36 are all 25 amino acids in length. Variants having at least 80% sequence identity would retain, minimally, 20 amino acids from the starting sequence(s).
Claims 27 and 31-43
Claim 27 is directed to a method for detecting SARS-CoV-2 S protein antigen-specific cell-mediated immune response activity in a biological sample from a subject. The method comprises:
Incubating in vitro an incubation test mixture comprising a biological sample comprising T- cells and APCs from the subject admixed with a first peptide composition comprising a first set of 15 isolated oligopeptides comprising SEQ ID NO: 22-36, or one or more variants thereof having at least 80% sequence identity thereto, each comprising a SARS-CoV-2 S protein RBD CD4+ T-cell epitope, under conditions and for a time sufficient for specific recognition by said T-cells of a SARS-CoV-2 S protein T-cell epitope that is present in the first composition to stimulate generation of a T-cell immune response indicator; and
Detecting a first level of the T-cell immune response indicator in the text mixture, wherein presence of SARS-CoV-2 S protein antigen-specific cell-mediated immune response activity in the sample is indicated by detection of said first level of the T-cell immune response indicator that is increased relative to a control level of the T-cell immune response indicator obtained by incubating the biological sample in a control incubation without the peptide composition, thereby detecting SARS-CoV-2 S protein antigen-specific cell-mediated immune response activity.
The biological sample is obtained from the subject before, after, or before and after a SARS-CoV-2 vaccination (claim 31). The sample comprises at least one of whole blood, among others (claims 32 and 33). The T-cell immune response indicator is IFN-γ, among others (claims 34, 36-39), released by the T-cells (claim 35) and detected by specific binding of a binding agent (claim 40), such as an antibody (claim 41), polyclonal or monoclonal (claim 42) immobilized on a solid phase (claim 43).
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.
Claims 5 and 45 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a law of nature without significantly more. The claims are directed to a composition comprising a set of 15 oligopeptides from SARS-CoV-2 RBD, represented by SEQ ID NO: 22-36. The characteristics of the oligopeptides are not markedly different from the product' s naturally occurring counterpart in its natural state the they conveys the same amino acid sequences. The oligopeptides do not appear to have been modified in any manner. The fact that the set of oligopeptides is not a natural combination is not relevant because the oligopeptides themselves are products of nature, and their presence together in a composition does not alter their structure or function.
This judicial exception is not integrated into a practical application, nor do the claims include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims are directed to compositions comprising the oligopeptides and nothing more. Further, the intended uses do not change the structure or function of the oligopeptides. Therefore, the claims are not patent eligible.
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 27 and 31-43 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 27, part (b) states “the biological sample is indicated by detection in (b) of said first level of the T-cell immune response indicator”. The reference within (b) to itself (i.e., (b)) is not clear, or is at least redundant. Further the reference to “said first level” lacks antecedent basis within the claim. The metes and bounds of the claim cannot be determined. Claims 31-43 are included in this rejection because they depend from claim 27.
Claim Rejections - 35 USC § 112
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.
Claims 27, 31-43 and 45 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains 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.
Claims 5 and 45 (elected species) are directed to a composition comprising a set of 15 isolated oligopeptides comprising SEQ ID NO: 22-36, or one or more variants thereof having at least 80% sequence identity thereto, each comprising a SARS-CoV-2 S protein RBD CD4+ T-cell epitope. The intended uses for the composition are:
Diagnosis of COVID-19
Prognosis of COVID-19
Detecting an antigen-specific T-cell mediated immune response to SARS-CoV-2
Claims 27-43 are directed to method for detecting SARS-CoV-2 S protein antigen-specific cell-mediated immune response activity in a biological sample from a subject, comprising incubating in vitro an incubation test mixture comprising a biological sample comprising T- cells and APCs from the subject admixed with a first peptide composition comprising a first set of 15 isolated oligopeptides comprising SEQ ID NO: 22-36, or one or more variants thereof having at least 80% sequence identity thereto, each comprising a SARS-CoV-2 S protein RBD CD4+ T-cell epitope, followed by detecting an antigen-specific T-cell mediated immune response to SARS-CoV-2.
The claims encompass a large genus of oligopeptide variants of SEQ ID NO: 22-36 having the ability to diagnose COVID-19, give a prognosis of COVID-19, and detect an antigen-specific T-cell mediated immune response to SARS-CoV-2. Each of SEQ ID NO: 22-36 are 25 amino acids in length. Variants having at least 80% sequence identity could differ at five amino acid positions from the starting sequence.
To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof.
In this case, Applicant has provided base sequences, SEQ ID NO: 22-36, and percent identity of at least 80%, coupled with a function of being a SARS-CoV-2 S protein RBD CD4+ T-cell epitope. In claims 5 and 45, the functions of the collective set of oligopeptides also include diagnosis of COVID-19, prognosis of COVID-19, and the detection of an antigen-specific T-cell mediated immune response to SARS-CoV-2, which is also represented in claims 27 and 31-43. There is no identification of any portion of any oligopeptide that may be changed, up to five amino acids, and still result in a SARS-CoV-2 S protein RBD CD4+ T-cell epitope, nor a collection of oligopeptides that can diagnose COVID-19, give a prognosis of COVID-19, and detect an antigen-specific T-cell mediated immune response to SARS-CoV-2.
The specification provides references to methods for determining variants (see paragraphs [0061]-[0062] of the published application US 2024/0027450), but does not appear to have made any nor shown them to have the claimed functions. The question here is whether Applicant has provided a representative number of species of the claimed genus. The only species provided is the base sequence, with no species to represent the genus of variants. Without a structure-function nexus, which has not been provided, one would not know where modifications may be made to the epitopes without changing their function as epitopes. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116). Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. One cannot describe what one has not conceived. This rejection may be overcome by limiting the claims to SEQ ID NO: 22-36.
Claims 5 and 45 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a composition, does not reasonably provide enablement for a composition for diagnosis of COVID-19, prognosis of COVID-19, and detect an antigen-specific T-cell mediated immune response to SARS-CoV-2. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The breadth of the claims encompasses a composition comprising a collection of 15 oligopeptides representing CD4+ T-cell epitopes from SARS-CoV-2 RBD. One of the composition’s intended uses is diagnosing COVID-19. The nature of the invention is that the detection of SARS-CoV-2 antigen-specific T-cell immune responsiveness, e.g., cytokines produced in response to stimulation by the collection of 15 oligopeptides, is an indicator of a subject’s T-cell response to SARS-CoV-2.
The specification discloses that methods of detecting active SARS-CoV-2 via PCR, and the detection of a past infection via antibodies, yield false-negatives due to various reasons, or are unreliable in the case of antibodies due to stages in the immune response, etc. (see paragraph [0005] of the published application US 2024/0027450). The specification indicates that the instant methods focus on T-cell immune responsiveness, and are useful for instances where the virus and/or antibodies have either been cleared or have been reduced (see paragraph [0006] of the published application). Based on these teachings, the collection of oligopeptides, alone, would not be useful for diagnosing COVID-19, which encompasses an active SARS-CoV-2 infection. The collection of oligopeptides, alone, would not be useful for giving a prognosis of a subject having COVID-19, which encompasses an active SARS-CoV-2 infection. The collection of oligopeptides, alone, would not be useful for detecting T-cell mediated immunity (i.e., a T-cell immune response indicator) in the absence of a means of detecting a T-cell immune response indicator. Example 2 of the specification shows T-cell mediated responses as measured by IFNγ in patients receiving a SARS-CoV-2 vaccine, however, there is no demonstration that the detection of the T-cell mediated responses is sufficient, alone, to diagnose COVID-19, to give a prognosis of COVID-19, or detect T-cell mediated immunity (i.e., a T-cell immune response indicator) in the absence of a means of detecting a T-cell immune response indicator.
Jaganathan et al. (Infect Dis Ther, 2021, 10:2765-2776, cited in the IDS filed 10/13/2023) discloses an assay similar to the one claimed in this application, noting that CD4+ and CD8+ T cell-mediated responses to SARS-CoV-2 in combination with a qualitative antibody response (see page 2765, Conclusion section). Stieber et al. (Pulmonology, 2023 Mar-Apr, 29(2):151-153), in disclosing results from an assay similar to the one claimed in this application, teaches that monitoring cellular immunity to COVID-19 is important in having a more comprehensive picture of a subject’s immune status as it pertains to vaccination (see page 151, left col., first paragraph, and page 152, right column, first paragraph). However, there is no indication that detecting T-cell mediated immunity alone would be sufficient to diagnose COVID-19 or give a prognosis of COVID-19.
Therefore, in view of the breadth of the claims, the nature of the invention, the limited teachings and working examples in the specification, the state of the art, and the low level of predictability with regard to the collection of oligopeptides being sufficient to accomplish the intended uses, it would require undue experimentation to use the claimed composition for its intended purposes. This rejection may be overcome by removing the intended uses from the claim language.
Conclusion
No claim is allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. WO2021/188969 (of record in the IDS filed 3/28/2025) discloses some of the peptides in the instantly claimed set of peptides, but not all of the peptides. WO2021/188969 discloses SEQ ID NO: 14863, 14964, 13243, 12905, 12699, 16577, 14208 and 12718, which correspond with 100% identity (or less, as indicated) to Applicant’s SEQ ID NO: 22, 23, 24, 25 (at 95% identity), 28, 29, 30 and 35, respectively.
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Any inquiry concerning this communication or earlier communications from the examiner should be directed to Stacy B. Chen whose telephone number is 571-272-0896. The examiner can normally be reached on M-F (7:00-4:30). If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Thomas Visone, can be reached on 571-270-0684. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
/STACY B CHEN/Primary Examiner, Art Unit 1672
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