DETAILED ACTION
Disposition of Claims
Claims 1-14 and 16-21 are pending.
Examiner’s Note
All paragraph numbers (¶) throughout this office action, unless otherwise noted, are from the US PGPub of this application US20230381295A1, Published 11/30/2023.
Applicant is encouraged to utilize the new web-based Automated Interview Request (AIR) tool for submitting interview requests; more information can be found at https://www.uspto.gov/patent/laws-and-regulations/interview-practice.
Optional Authorization to Initiate Electronic Communications
The Applicant’s representative may wish to consider supplying a written authorization in response to this Office action to correspond with the Examiner via electronic mail (e-mail). This authorization is optional on the part of the Applicant’s representative, but it should be noted that the Examiner may not initiate nor respond to communications via electronic mail unless and until Applicant’s representative authorizes such communications in writing within the official record of the patent application. A sample authorization is available at MPEP § 502.03, part II. If Applicant’s representative chooses to provide this authorization, please ensure to include a valid e-mail address along with said authorization.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-(d) prior to declaration of an interference, a certified English translation of the foreign application must be submitted in reply to this action. 37 CFR 41.154(b) and 41.202(e).
Failure to provide a certified translation may result in no benefit being accorded for the non-English application.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 10/24/23 and 11/10/23 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Notably, the disclosure statement filed lists a Search Report. The listing of the references cited in a Search Report itself is not considered to be an information disclosure statement (IDS) complying with 37 CFR 1.98. 37 CFR 1.98(a)(2) requires a legible copy of: (1) each foreign patent; (2) each publication or that portion which caused it to be listed; (3) for each cited pending U.S. application, the application specification including claims, and any drawing of the application, or that portion of the application which caused it to be listed including any claims directed to that portion, unless the cited pending U.S. application is stored in the Image File Wrapper (IFW) system; and (4) all other information, or that portion which caused it to be listed. In addition, each IDS must include a list of all patents, publications, applications, or other information submitted for consideration by the Office (see 37 CFR 1.98(a)(1) and (b)), and MPEP § 609.04(a), subsection I. states, "the list ... must be submitted on a separate paper." Therefore, the references cited in the Search Report have not been considered. Applicant is advised that the date of submission of any item of information or 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 IDS, including all "statement" requirements of 37 CFR 1.97(e). See MPEP § 609.05(a).
Note: If copies of the individual references cited on the Search Report are also cited separately on the IDS (and these references have not been lined-through) they have been considered.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. 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. See ¶[0002] “ www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports ” ; ¶[0003] “ https://doi.org/10.1016/j.cell.2020.02.058 “; ¶[0147] “ https://rpcec.sld.cu/trials/RPCEC00000347-En “; “ https://rpcec.sld.cu/trials/RPCEC00000374-En “; ¶[0149] “ https://rpcec.sld.cu/trials/RPCEC00000360-En “
Specification - Drawings
The drawings are objected to because: Figures 1-2 reference color (See ¶[0038-0039]). Corrected drawing sheets in compliance with 37 CFR 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 CFR 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.
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains reference to at least one drawing executed in color (See e.g. ¶[0038-0039] and Figs. 1-2). Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Claim Objections
Claim 1 is objected to because of the following informalities: the definition of the abbreviation “SARS CoV-2” is not provided. For clarity, it is requested that the first recitation of an abbreviation within a claim set be preceded by its full-length name (i.e. … severe acute respiratory syndrome coronavirus type 2 (SARS CoV-2”...).
Appropriate correction is required.
Claim 6 is objected to because of the following informalities: there are grammatical informalities in the Markush grouping, the claim should ideally read: “…mammalian cells, insect cells, bacterial cells, and yeast cells.” Appropriate correction is required.
Claim Rejections - 35 USC § 112(b); Second Paragraph
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 5 and 13 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 5 provides for “The covalent conjugate of claim 4, wherein the RBD of SEQ ID NO:1 is used in its dimeric form.” However, claim 4 is drawn to RBD sequences from naturally-occurring SARS CoV-2 S proteins and is dependent upon claim 1, and claim 1 is drawn to a covalent conjugate of a SARS CoV-2 RBD and a carrier protein. The breadth of claim 1 allows the conjugate to comprise a protein-carrier protein conjugate, wherein the protein conjugated to the carrier must “comprise” the RBD, which means the full-length SARS CoV-2 S protein could be bound to a carrier protein and still read upon claim 1 and dependent claims 4-5. The full-length S protein forms trimers, not dimers, and when the RBD is expressed on its own as a recombinant protein, it is naturally a monomer but can dimerize when it is just the RBD domain (a fragment of the full-length S protein that encompasses about aa 319-541). Therefore, the wording of claim 5 is confusing, because under at least one reasonable interpretation, the RBD is within another longer amino acid sequence that may or may not be able to form a dimer. It is suggested that claim 5 be amended to recite that the RBD of claim 1 consists of a certain sequence or length (e.g. …wherein the RBD consists of SEQ ID NO:1, and the RBD is in a dimeric form.”) Alternatively, claim 1 may be amended to reduce the RBD to only that sequence which consists of only the RBD. Claim 13 is rejected for similar reasoning.
For at least these reasons, claims 5 and 13 are rejected on the grounds of being indefinite.
Claim 6 is 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 6 recites: “The covalent conjugate according to claim 1, wherein the RBD is produced in a host selected from the group consisting of: mammal cells, insect cells, bacterial and yeasts.” The use of “host” normally refers to a living being in the art, while the use of “host cells” refers to cells that have been taken/isolated from a living host and are propagated in vitro. The Markush group appears to refer to “cells”, so it is unclear if these are cells that are meant to be inserted into a host and grown to propagate the covalent conjugate, or if the intent is to claim “host cells” for propagation in vitro. From the guidance in the specification, and from the claim objection supra, it appears as though the latter interpretation is correct, and it is suggested the claim be amended along the following lines:
“The covalent conjugate according to claim 1, wherein the RBD is produced in a host cell selected from the group consisting of: mammalian cells, insect cells, bacterial cells, and yeast cells.”
For at least these reasons, claim 6 is rejected on the grounds of being indefinite.
Claim 13 is 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 13 recites the limitation "RBD dimers" in line 2. There is insufficient antecedent basis for this limitation in the claim.
Claim Interpretation
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art.
Claim 1 is drawn to a covalent conjugate comprising a severe acute respiratory syndrome coronavirus type 2 (SARS CoV-2) receptor-binding domain (RBD) and a carrier protein.
Further limitations on the covalent conjugate of claim 1 are wherein the carrier protein is selected from the group consisting of tetanus toxoid, diphtheria toxoid, and diphtheria toxoid mutant CRM197 (claim 2); wherein the RBD-carrier protein molar ratio is within the range of 1 to 8 RBD per carrier protein (claim 3); wherein the RBD is selected from the group consisting of SEQ ID NOs: 1, 2 and 3 (claim 4), wherein the RBD of SEQ ID NO:1 is in its dimeric form (claim 5); and wherein the RBD is produced in a host cell selected from the group consisting of: mammalian cells, insect cells, bacterial cells, and yeast cells (claim 6).
Claim 7 is drawn to a vaccine composition used to induce an immune response against SARS- CoV-2 comprising the covalent conjugate of claim 1.
Further limitations on the vaccine composition of claim 7 are wherein the vaccine composition comprises an adjuvant selected from the group consisting of: aluminum hydroxide, aluminum phosphate and calcium phosphate (claim 8), wherein the adjuvant is in a concentration range of 200-1500 ug per dose (claim 10); wherein the conjugate is in a concentration range of RBD 1-30 ug per dose (claim 9); and wherein the vaccine composition comprises appropriate pharmaceutical excipients (claim 11).
Claim 12 is drawn to a method of preparing the covalent conjugate of claim 1 comprising:
A) functionalizing the carrier protein by introducing thiophilic groups;
B) covalently conjugating the carrier protein to the RBD, and
C) purifying the covalent conjugate.
Further limitations on the method of claim 12 are wherein the method is further comprising in situ reduction of RBD dimers prior to step A, optionally wherein SEQ ID NO:1 is used (claim 13); further comprising thiolation of the RBD N-terminus prior to step A (claim 14), wherein the RBD is selected from the group consisting of: SEQ ID NOs: 1, 2 and 3 (claim 16); and wherein the thiophilic groups introduced at step A are selected from the group consisting of: maleimide, bromoacetyl, vinylsulphone, acrylate, acrylamide, acrylonitrile, and methacrylate (claim 17).
Claim 18 is drawn to a conjugate obtained according to the method of claim 12.
Claim 19 is drawn to a method of preventing infection with the SARS-CoV-2 virus in a subject, comprising administering the vaccine composition of claim 7 to the subject.
Claim 20 is drawn to a method of preventing infection with the SARS-CoV-2 virus in a subject, comprising administering two doses of the vaccine composition of claim 7 to the subject.
Claim 21 is drawn to a method of inducing a SARS-CoV-2 antibody response in a subject, comprising: administering 1 to 3 doses of the vaccine composition of claim 7 to the subject, wherein the administration is intramuscular, and wherein each dose comprises from 1 to 30 ug RBD.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-2, 4, 7-12, and 17-21 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Xie et. al. (US20230330220A1; Priority 05/01/2020; hereafter “Xie”.)
The Prior Art
Xie teaches methods for improving the immunogenicity of a protein/peptide antigen, wherein the method comprises conjugating a protein/peptide antigen with a sugar to form a sugar-protein/peptide antigen conjugate, which has improved immunogenicity compared to an unconjugated protein/peptide antigen (entire document; see abstract.) Xie teaches the protein or peptide antigen may be conjugated to a carrier protein, such as diphtheria toxoids, such as CRM197 (¶[0006]). Xie teaches the protein or peptide antigen may be a viral antigen from a coronavirus (CoV) spike (S) protein, preferably from the receptor binding domain (RBD) (reference claim 3), wherein the CoV is SARS CoV-2 (reference claim 4). As Xie teaches the protein/peptide conjugated to a saccharide to make a glycol-protein/peptide conjugate may be further conjugated to a carrier protein such as CRM197 (reference claims 1, 24-25; ¶[0238]), and teaches that said conjugates may be immunogenic compositions (reference claim 50; ¶[0149]), Xie teaches every limitation as required by instant claims 1-2, and 7.
Xie teaches the weight of antigen to carrier protein is 2.7 mg:0.3 mg, or about 9:1 (Table 2). Xie teaches SEQ ID NO: 2, which is 100% identical to instant SEQ ID NO: 1 (¶[0035]; reference claim 6; instant claim 4). Xie teaches aluminum adjuvants may be used (¶[0150]; reference claim 51), such as aluminum phosphate or aluminum hydroxide (¶[0207]; instant claim 8). The dose used to immunize may be about 1-3 ug in mice (¶[0253]; Table 3; instant claim 9) The aluminum adjuvant was at a concentration of 1 mg/mL, and added to an equal volume of antigen at either 0.02 mg/mL or 0.06 mg/mL, resulting in compositions of 0.5 mg/mL (500 ug/mL) aluminum adjuvant and 0.01 mg/mL or 0.03 mg/mL antigen (Sect. 5.1.3, ¶[0245]; instant claim 10). Xie teaches the composition may also comprise appropriate pharmaceutical excipients (¶[0149]; reference claim 50; instant claim 11). Xie teaches the method of making the conjugates, such as activating the moieties with divinyl sulfone (¶[0203-0206]; instant claims 12, 17-18). Xie teaches methods of preventing SARS CoV-2 infection through intramuscular prophylactic vaccination of the protein conjugate to a subject in need thereof (¶[0210]; instant claims 19, 21), wherein the vaccination may be a single dose or a prime-boost vaccination regimen (¶[0211]; instant claim 20).
Xie therefore teaches the limitations of instant claims 1-2, 4, 7-12, and 17-21, and anticipates the invention encompassed by said claims.
Claims 1-3, 6-7, and 19 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Bellone et. al. (Bellone ML, et. al. Biochem Biophys Res Commun. 2021 Jun 18;558:79-85. Epub 2021 Apr 20.; hereafter “Bellone”.) NB: The certified copy of the foreign priority document of the instant application is not in English; this rejection may be overcome as noted supra by the filing of an English copy of said priority document.
The Prior Art
Bellone teaches conjugation of the receptor binding domain (RBD) of COVID-19 spike protein (SP) to CRM197, a variant of diphtheria toxin currently used for a number of conjugated vaccines, wherein said conjugate can be generated in Escherichia coli (E.coli) and has a proposed use as a vaccine against SARS CoV-2 (entire document; see abstract; instant claims 1-2, 6-7, 19). Bellone teaches that the CRM197 is generated as a construct that is directly fused to the RBD, making the molar ratio 1:1 (Fig. 1; instant claim 3).
For at least these reasons, Bellone teaches the limitations of instant claims 1-3, 6-7, and 19, and anticipates the invention encompassed by said claims.
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.
The factual inquiries 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.
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 as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention 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.
Claims 5, 13-14, and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Xie as applied to claims 1-2, 4, 7-12, and 17-21 above, and further in view of
Starr et. al. (Starr TN, et. al. Cell. 2020 Sep 3;182(5):1295-1310.e20. Epub 2020 Aug 11.; hereafter “Starr”); and
Neville et. al. (US20130211049A1; Pub. 08/13/2015; hereafter “Neville”.)
The Prior Art
The teachings of Xie have been set forth supra. Xie teaches RBD-CRM197 conjugates can be formed after separate expression and isolation of the RBD and CRM197 products. Xie teaches generically the methods of making the conjugates, such as the use of activating the products with divinyl sulfone. However, Xie fails to teach that the RBDs can be expressed as dimers with only the portion of the RBD from the SARS CoV-2 S protein, nor does Xie teach the explicit thiolation of the N-terminus of either the RBD or CRM197 products. However, these methods of formulating conjugates was known in the art, as evidenced by Neville, and the formulation of RBD dimers was also known in the art, as evidenced by the teachings of Starr.
Neville teaches recombinant diphtheria toxin (DT)-based immunotoxins and fusion proteins thereof (entire document; see abstract). Neville teaches the derivative of DT, CRM197, as a less toxic version of DT, and that CRM197 is commonly used for immunization (¶[0140-0145]). Neville teaches that the fusion proteins of DT to the additional protein can be made by thiolating both the DT moiety and additional protein moiety and then crosslinking the bismaleimide crosslinkers (¶[0251][0342]). Neville teaches methods to generate monomeric units of the moieties (¶[0342]).
Starr teaches deep mutational scanning of SARS CoV-2 S protein RBD, wherein every amino acid was systematically changed to determine the effect on receptor binding to ACE2 (entire document; see abstract.) Starr teaches recombinant expression of the RBD on the surface of yeast (p. 1296, “Yeast Display of RBDs from SARS-CoV-2 and Related Sarbecoviruses”; Fig. 1.) Starr teaches that the RBD in its non-reduced form can form dimers (Fig. S4G; Fig. 4 E-F).
Given the teachings from Xie, one of skill in the art would be apprised as to the immunogenic nature of RBD-CRM197 as vaccine antigens for SARS CoV-2. Given the teachings of Xie, one of skill in the art would be apprised as to methods to generate RBD-CRM197 conjugates through thiolation of the moieties, and more specifics on such a method are taught by Neville. Given the teachings of Starr, one of skill in the art would be apprised to the fact that RBD expressed on its own, apart from full-length S protein, could form homodimers that would be eliminated upon reduction of the RBD. Therefore, taking the combined teachings of Xie, Neville, and Starr, one of skill in the art would find arriving at the limitations of instant claims 5, 13-14, and 16 obvious.
It would have been obvious to one of ordinary skill in the art to modify the methods and compositions taught by Xie in order to use specific methods of thiolation to crosslink the separate carrier protein to its protein antigen, thereby generating such immunogenic complexes as RBD-CRM197. One would have been motivated to do so, given the suggestion by Neville that methods for performing such a union of two proteins were known in the art. There would have been a reasonable expectation of success, given the knowledge that one would have to reduce the RBD before the process to remove any errant RBD homodimers, as taught by Starr, and also given the knowledge that RBD-CRM197 was able to be formulated in a similar process and was highly immunogenic, as taught by Xie. Thus, the invention as a whole was clearly prima facie obvious to one of ordinary skill in the art at the time the invention was made.
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.
Claims 1-14 and 16-21 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of copending Application No. 18/021,731 in view of Del Giudice et. al. (US20150165019A1, Pub. 06/18/2015; hereafter “Del Giudice”.) Both sets of claims are drawn to covalent conjugates which comprise the RBD of SARS CoV-2 S protein bound to an immunopotentiating components. Both sets of claims provide for the compositions to comprise adjuvants, such as aluminum hydroxide, and RBDs with the same sequences. Both sets of claims provide that the RBD may or may not be in the form of a dimer. Both sets of claims are drawn to similar concentrations of RBD in the composition, along with the presence of pharmaceutical excipients. Both sets of claims are drawn to methods of using the compositions in therapeutic or prophylactic immunization against SARS CoV-2 in one to three doses. The main difference is that the ‘731 claims provide for the use of Neisseria meningitidis Group B bacterial outer membrane vesicles (OMVs), while the instant claims provide that the RBD is covalently bound to a carrier protein, namely CRM197. However, the use of one or the other, or both in combination, was well-known in the art, as evidenced by the teachings of Del Giudice. Del Giudice teaches compositions comprising a combination of two or more monovalent conjugates, each of said two or more monovalent conjugates comprising a carrier protein comprising T cell epitopes from two or more pathogens conjugated to saccharide antigen (entire document; see abstract.) Del Giudice teaches the antigen may be from a coronavirus such as SARS CoV spike (S) protein antigen (¶[0097][0111-0113]), and that the carrier protein may be CRM197 (reference claims 1-2; ¶[0005][0024][0054][0122]) and the saccharide (or further protein) antigen may be outer membrane complexes Neisseria meningitidis Group (reference claims 1-20; ¶[0005][0019][0079].) Given that OMV and CRM197 were carriers commonly used already in the vaccine art to render viral antigens more immunogenic (¶[0005]), it would be obvious to a skilled artisan to attach one or both of these antigens to the shorter RBD SARS CoV-2 peptide to ensure its stability and immunogenicity in vaccine formulations. Therefore, the differences between the instant claims and the ‘731 claims are not patentably distinct, especially in light of the teachings of Del Giudice.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RACHEL B GILL whose telephone number is (571)272-3129. The examiner can normally be reached on M to F 8:00 AM to 5:00 PM Eastern.
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/RACHEL B GILL/
Primary Examiner, Art Unit 1671