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 .
DETAILED ACTION
Priority
This patent application is a U.S. National Phase of International Patent Application No. PCT/EP2022/068951, filed July 7, 2022, which claims priority to European Patent Application No. 21184298.4, filed July 7, 2021, that is hereby acknowledged by the Examiner.
Status of the Claims
The amendment dated 01/05/2024 is acknowledged. Claims 1-16 and 18-19 are pending and under examination.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 03/18/2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement(s) is/are being considered by the Examiner.
Drawings
The drawing filed on 01/05/2024 are acknowledged and accepted by the Examiner.
Specification
The disclosure is objected to because of the following informalities: The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (see pages 19-20 and 57). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01. Appropriate correction is required.
Claim Objections
Claims 8 and 10 are objected to for the following informalities:
Claims 8 and 10 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
Claims 1-7, 9, 11-16 and 18-19 are rejected under 35 U.S.C. 103(a) as being unpatentable over Pino et al. “Pino” (Processes, 2020, 8(12):1539, IDS of record dated 03/18/2024) in view of Fan et al. “Fan” (THE FASEB J., 2004, 279(8):6534-6539, IDS of record dated 03/18/2024) and further in view of Kongerslev et al. “Kongerslev” (WO2004089394A2, IDS of record dated 03/18/2024).
The claims are directed to a multimeric protein complex comprising three polypeptides each comprising N- to C-terminally:
(i) a receptor-binding domain (RBD) of an S1 subunit of a Spike (S) protein of a coronavirus,
(ii) optionally a S2 subunit of an S protein of a coronavirus; and
(iii) a multimerization domain comprising a collagen-like region (CLR) of ficolin-2, wherein the multimerization domain enables the assembly of the polypeptides into a trimeric protein complex.
Regarding claims 1-7, 9, 11-16 and 18-19, Pino discloses a trimeric SARS-CoV-2 spike protein comprising a RBD domain having a full S1 and S2 which is fused to a T4 foldon, a his tag, and has a mutated furin cleavage site (Abstract, Fig. 1 below and Table 1). Pino also discloses the medical use of spike trimers for the treatment of SARS-CoV-2 as a vaccine (Abstract).
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Pino does not teach wherein the domain comprises a collagen-like region of ficolin-2.
Fan, however, discloses “a class of multivalent protein binders was designed to overcome the limitations of low-affinity therapeutic antibodies. These binders, termed “collabodies,” use a triplex-forming collagen-like peptide to drive the trimerization of a heterologous target-binding domain; and the trimeric collagen scaffold does not compromise the functionality of the binding moieties of parental immunoglobulin G (IgG); therefore, it could be applied to fuse other protein molecules to acquire significantly improved targeting binding strengths” (Abstract). Fan teaches that “multimerization significantly increases the avidity of the binding domain of these defense collagen molecules. Therefore, it seems to be a feasible approach to use a collagen-like domain as scaffold to create a range of designer protein drugs that have improved therapeutic properties” (page 3796 first column, first para.). Further, in view of Kongerslev, discloses “the use of subunits and oligomers of collectins and/or ficolins, such as mannan-binding lectin (MBL) in prophylactic and /or curative treatment of Severe Acute Respiratory Syndrome (SARS) in an individual” (Abstract); and “Serum ficolins have a common binding specificity for GlcNAc (N-acetyl- glucosamine), elastin or GalNAc (N-acetyl-galactosamine). The fibrinogen-like domain is responsible for the carbohydrate binding. In human serum, two types of ficolin, known as L-ficolin (P35, ficolin L, ficolin 2 or hucolin) and H-ficolin (Hakata anti- gen, ficolin 3 or thermolabile b2-macroglycoprotein), have been identified, and both of them have lectin activity” (page 2 lines 31-35) and that ficolin is a cysteine-rich sequence (page 18 section “Ficolins”). Kongerslev discloses the gene expression construct may be produced by conventional methods know to the skilled person (i.e. recombinant DNA technology) (page 30 lines 11-15 and claims 12 and 32 of Kongerslev). Kongerslev states “SARS may be prevented and/or treated in individuals independent on their serum collectin and/or ficolin level” (page 5 lines 18-19).
Accordingly, it would have been obvious to one of ordinary skill in the art to generate a multimeric protein complex comprising three polypeptides each comprising N- to C-terminally: (i) a receptor-binding domain (RBD) of an S1 subunit of a Spike (S) protein of a coronavirus, (ii) optionally a S2 subunit of an S protein of a coronavirus as disclosed by Pino; and (iii) a multimerization domain comprising a collagen-like region (CLR) of ficolin-2, wherein the multimerization domain enables the assembly of the polypeptides into a trimeric protein complex as disclosed by Kongerslev and Fan. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success given the knowledge that Fan states “a class of multivalent protein binders was designed to overcome the limitations of low-affinity therapeutic antibodies… multimerization significantly increases the avidity of the binding domain of these defense collagen molecules. Therefore, it seems to be a feasible approach to use a collagen-like domain as scaffold to create a range of designer protein drugs that have improved therapeutic properties” (page 3796 first column, first para.); and given the fact that Kongerslev states “the use of subunits and oligomers of collectins and/or ficolins, such as mannan-binding lectin (MBL) in prophylactic and /or curative treatment of Severe Acute Respiratory Syndrome (SARS) in an individual” (Abstract), whereby “SARS may be prevented and/or treated in individuals independent on their serum collectin and/or ficolin level” (page 5 lines 18-19). Therefore, the claimed invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Barry Chestnut whose telephone number is (571)270-3546. The examiner can normally be reached on M-Th 8:00 to 4:00.
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.
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/BARRY A CHESTNUT/Primary Examiner, Art Unit 1672
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