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 .
Status of the claims
The amendment filed 10/02/23 is acknowledged and has been entered. Claims 1-9, 11-13, 15-18 and 20 have been canceled. Claims 10, 14, 19, and 21-22 have been amended. New claims 23-36 have been added. Accordingly, claims 10, 14, 19 and 21-36 are pending and under examination.
Information Disclosure Statement
The information disclosure statement (IDS), filed 08/25/22 fails to comply with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609 because citations no. 4 to Wu et al and no. 5 to Yan et al lacks readable references. Although it appears the applicant tried to provide the two references the references provided cannot be read because the descriptions are too blurry and also too small. Therefore, the references cannot be reviewed and thus the merits of the Wu et al reference and the Yan et al reference cannot be ascertained. The IDS has been placed in the application file, and the information referred to therein has been considered as to the merits, but the citations have been lined through on the said IDS. Applicant is advised that the date of any re-submission of any item of information contained in this information disclosure statement or the submission of any missing element(s) will be the date of submission for purposes of determining compliance with the requirements based on the time of filing the statement, including all certification requirements for statements under 37 CFR 1.97(e). See MPEP § 609.05(a).
Specification
The use of the term Tween 20 (e.g. para’s 0132, 0178), which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
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.
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.
Written Description
Claims 10, 14, 19 and 21-36 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The methodology for determining adequacy of Written Description to convey that applicant was in possession of the claimed invention includes determining whether the application describes an actual reduction to practice, determining whether the invention is complete as evidenced by drawings or determining whether the invention has been set forth in terms of distinguishing identifying characteristics as evidenced by other descriptions of the invention that are sufficiently detailed to show that applicant was in possession of the claimed invention (Guidelines for Examination of Patent Applications under 35 USC § 112, p 1 “Written Description” Requirement; (Federal Register/Vol 66. No. 4, Friday, January 5, 2001; II Methodology for Determining Adequacy of Written Description (3.)).
Claim 10 is broadly drawn, such that they apply to a genus of polypeptides and proteins consisting of the sequence shown in SEQ ID NO:1 and also to a genus of amino acid sequences having a sequence having a sequence identity of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or at least 100% compared to SEQ ID NO: 1.
However, the working examples provided in the instant application only demonstrate specific species of 2019-nCoV S-RBD isolated polypeptide consisting of SEQ ID NO: 1 which possess the unique capability of specifically binding to 2019-nCoV-specific IgM antibody. Despite the large variety of partial sequences, fragments thereof and homologue sequences that could be constructed, the specification only cites possession of the specific 2019-nCoV S-RBD isolated polypeptide consisting of SEQ ID NO: 1 which possess the unique capability of specifically binding to 2019-nCoV-specific IgM antibody.
It was known in the prior art that small changes in antigen structure profoundly affect antibody-antigen interactions. Harlow & Lane (Harlow, E. and Lane, D., Antibodies: A Laboratory Manual (1988) Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, pages 23-26) discuss how even small changes in antigen structure can profoundly affect the strength of an antibody-antigen interaction. See entire selection, in particular page 26, first full paragraph. In particular, the loss of a single hydrogen bond can reduce the strength of interaction by 1000-fold (ibid). Further, as shown by He et al (Biochemical and Biophysical Research Communications, 344, 2006, pages 106-113 a single amino acid substitution in the receptor-binding domain of SARS coronavirus spike protein disrupts the antigenic structure and binding activity (e.g. page 106).
Many other researchers have reported similar findings to those of Harlow & Lane. For example, Lederman et al. ("A single amino acid substitution in a common African allele of the CD4 molecule ablates binding of the monoclonal antibody, OKT4" Mol Immunol. 1991 Nov;28(11):1171-81) found that a single amino acid substitution on the antigen CD4 ablated binding of a monoclonal antibody (see title and abstract). Similarly, Colman et al. (Research in Immunology, 1994; 145(1): 33-36) teach that amino acid changes in an antigen can effectively abolish antibody antigen binding entirely (see entire document, particularly pages 33-34).
As noted above, the variability among the protein sequences encompassed by the claims is also enormous; and would encompass changes much more substantial than the loss of a single hydrogen bond or the mutation of a single amino acid; yet even such minor changes as these were known to dramatically affect function.
Given the unpredictability associated with making even minor changes to antigen structure while preserving function, with limited exception it is not possible to predict which, out of the enormous number of peptides encompassed by the claims, would be capable of binding to autoantibodies of rheumatoid arthritis.
MPEP § 2163, states “[A] biomolecule sequence described only by a functional characteristic, without any known or disclosed correlation between that function and the structure of the sequence, normally is not a sufficient identifying characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence.”
The Revised Interim Guideline for Examination of Patent Applications under 35 USC § 112, p1 “Written Description” Requirement (Federal Register/ Vol 66. No 4, Friday January 5, 2001) states “The claimed invention as a whole may not be adequately described if the claims require an essential or critical element which is not adequately described in the specification and which is not conventional in the art” (column 3, page 71434), “when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus”, “In an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus” (column 2, page 71436, emphasis added).
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states that “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 the [he or she] invented what is claimed.” (See Vas-Cath at page 1116).
One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481, 1483. In Fiddes, claims directed to mammalian FGF's were found to be unpatentable due to lack of written description for that broad class. The specification provided only the bovine sequence.
Considering the potentially large numbers of polypeptide and proteins comprising this sequence and sequences encompassed by partial sequences, and homologues of sequences of 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% homology or more, the disclosure is not sufficient to show that a skilled artisan would recognize that the applicant was in possession of the claimed invention (genus) commensurate to its scope at the time the application was filed. It appears that the specification is limited to 2019-nCoV S-RBD isolated polypeptide consisting of SEQ ID NO: 1 which possess the unique capability of specifically binding to 2019-nCoV-specific IgM antibody.
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 10, 14, 19 and 21-36 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 10 is indefinite in reciting improper Markush language in reciting “the detection reagent and capture reagent are each independently selected from” because it appears to intend to limit the scope of the detection reagent and capture reagent in the claims but improperly defines it as such. Perhaps, Applicant intends, “the detection reagent and capture reagent are each selected from the group consisting of an isolated polypeptide and a fusion protein …”.
Claim 19 provides for the use of the kit of claim 105, but, since the claim does not set forth any steps involved in the method/process, it is unclear what method/process applicant is intending to encompass. A claim is indefinite where it merely recites a use without any active, positive steps delimiting how this use is actually practiced.
Claim 19 is rejected under 35 U.S.C. 101 because the claimed recitation of a use, without setting forth any steps involved in the process, results in an improper definition of a process, i.e., results in a claim which is not a proper process claim under 35 U.S.C. 101. See for example Ex parte Dunki, 153 USPQ 678 (Bd.App. 1967) and Clinical Products, Ltd. v. Brenner, 255 F. Supp. 131, 149 USPQ 475 (D.D.C. 1966).
Claim 23, the phrase "optionally" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(h).
The term optionally means "not required or mandatory". For example, a composition comprising A, B, C, and optionally D means that component D can or cannot be present (D is not required to be present). In the rejected claim 23, however, it appears the use of "optionally" is an attempt to define "preferred" embodiments or limitations. For example, claim 23 states “…optionally via a linker”. In this instance, the term optionally does not make sense given the definition of optionally (not required or mandatory).
Accordingly, one of ordinary skill in the art will not know the metes and bounds of the claim.
Claim 25 is indefinite in reciting improper Markush language in reciting “the additional polypeptide is selected from” because it appears to intend to limit the scope of the additional polypeptide in the claims but improperly defines it as such. Perhaps, Applicant intends, “the additional polypeptide is selected from the group consisting of ….”.
Allowable Subject Matter
Claims 10, 14, 19 and 21-36 are would be allowable if rewritten or amended to overcome the rejection(s) under 35 U.S.C. 112(a), and 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), 2nd paragraph, set forth in this Office action. The closest prior art of record is considered to be Chen et al (Eur J Clin Microbiol Infect Dis, (2005), 24, pages 549-553) which teaches a SARS-CoV immobilized antigen and a labeled antigen for use in a double-antigen sandwich immunoassay for the detection of antibodies (e.g. abstract, pgs 549-550). However, Chen et al does not teach nor fairly suggest an isolated polypeptide consisting of the sequence shown in SEQ ID NO:1.
Conclusion
No claims are allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Cao et al (Virology Journal, 2010, 7:299, pages 1-6) (submitted in the IDS filed 05/24/24) discloses recombinant RBD protein used in an ELISA assay to detect antibodies (e.g. abstract, page 2).
Wang et al (Clinical Immunology, 113, (2004), pages 145-150 discloses recombinant fragments of S proteins from SARS-CoV and the use in ELISA (e.g. abstract, pg 147).
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/GARY COUNTS/ Primary Examiner, Art Unit 1678