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 .
Drawings
The drawings are objected to because Figure 2 has an amino acid sequence without a required sequence identifier (SEQ ID NO).
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.
In lieu of filing a replacement drawing, the specification may be amended to reference the sequence identifier in the brief description of the figures.
Claims Summary
Claim 1 is directed to a fusion protein comprising:
A coronavirus-derived receptor-binding domain (RBD); the coronavirus is SARS-CoV-2 (claim 9); the domain comprises SEQ ID NO: 1 (claim 2); SEQ ID NO: 1 represents a wildtype SARS-CoV-2 RBD;
A nucleocapsid protein (N); see paragraph [0062] of the published application, US 20240082387 for a definition of “nucleocapsid”, which indicates that N proteins in this application refer to coronavirus N proteins); the N protein is represented by SEQ ID NO: 4 (claim 3); SEQ ID NO: 4 represents a SARS-CoV-2 NC; and
An Fc domain; the Fc domain is an IgG Fc domain (claim 4); the Fc domain comprises SEQ ID NO: 2.
The RBD is linked to at least one of an N-terminus and a C-terminus of the Fc domain (claim 6), and the NP is linked to the remaining terminus (claim 7). The fusion protein is a dimer of an Fc domain to which the RBD and NC are linked (claim 8). Also claimed is a vaccine comprising the fusion protein (claim 10), and an adjuvant (claim 11), such as an aluminum salt, among others (claim 12). Also claimed is a pharmaceutical composition for preventing or treating a coronavirus infection, comprising the fusion protein as an active ingredient (claim 13). The infection is COVID-19 (claim 14).
Also claimed is a nucleic acid encoding the fusion protein (claim 15), a recombinant vector (claim 16), and a host cell (claim 17). Claim 18 is directed to a method for producing a fusion protein, comprising culturing the host cell and obtaining the fusion protein produced.
Claims 19 and 20 are directed to a method for vaccination, or preventing or treating coronavirus infection, comprising administering the vaccine composition or pharmaceutical composition to a subject, respectively.
Claim 21 is directed to use of the fusion protein for manufacture of a vaccine composition. Claim 22 is directed to use of the fusion protein for manufacture of a pharmaceutical composition for preventing or treating coronavirus infection.
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 21 and 22 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The claims are written as “use” claims that do not fall within at least one of the four categories of patent eligible subject matter because they do not purport to claim a process, machine, manufacture of composition of matter. See MPEP 2173.05(q).
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 21 and 22 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. Claims 21 and 22 are written as “use” claims that do not recite any active, positive steps delimiting how the use is actually practiced. See MPEP 2173.05(q).
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 10-14, 19 and 20 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 that induces an immune response against coronavirus, or more specifically SARS-CoV-2 in some embodiments, and a method of inducing an immune response against a coronavirus, or more specifically SARS-CoV-2 in some embodiments, does not reasonably provide enablement for a vaccine, pharmaceutical composition that prevents or treats, method of vaccination, method of preventing, or method of treating any coronavirus infection. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make or use the invention commensurate in scope with these claims.
The breadth of the claims encompasses a vaccine composition, which is understood to be capable of inducing an immune response that, upon challenge, will provide protective immunity such that the subject will not develop disease. The claims also encompass a pharmaceutical composition that will prevent any coronavirus infection, or treat any existing coronavirus infection. Also encompassed are methods of preventing or treating any coronavirus infection. The vaccine and pharmaceutical compositions encompass a fusion protein comprising an RBD of any coronavirus, a coronavirus N protein (see paragraph [0062] of the published application, US 20240082387 for a definition of “nucleocapsid”), and an Fc domain. Thus, the claims encompass a broad spectrum of fusion proteins, as well as a broad spectrum of coronavirus prevention and treatment.
To illustrate how broad the claims are, take for example, a fusion protein comprising an Fc domain, an RBD from HKU1, and an N protein from MERS. Such a construct is, according to the breadth of the claims, capable of inducing protective immunity against the common cold caused by HCoV-229E, and is also capable of treating an existing SARS-CoV-2 infection. As another example, a fusion protein comprising an Fc domain, an RBD from SARS-CoV, and an N protein from HCoV-NL63, is, according to the breadth of the claims, capable of inducing protective immunity against MERS, and treating an existing common cold caused by an infection with HCoV-OC43, HCoV-229E and HKU1.
The nature of the invention is the induction of an immune response that will serve to protect against disease upon subsequent infection, or that will improve the condition of a subject already infected and experiencing disease symptoms.
The specification is focused on SARS-CoV-2, while also mentioning other coronaviruses. As for guidance for the prevention or treatment of coronaviruses besides SARS-CoV-2, paragraph [0122] of the published application asserts that a SARS-CoV (SARS-CoV-1) can be used for the prevention and treatment of all coronavirus infections because of the mechanism by which it enters (i.e., binding of ACE2 and spike protein). Besides this, there is no further guidance, nor working examples that speak to non-SARS-CoV-2 embodiments, nor evidence of the extent of cross-reactivity and cross-protection across the various coronaviruses. The examples in the specification are limited to SARS-CoV-2 constructs, wherein the RBD and N proteins are from SARS-CoV-2. The SARS-CoV-2 constructs are shown to be immunogenic in the examples.
The prior art does not recognize a vaccine, nor a treatment comprising a vaccine, for the common cold caused by coronaviruses HCoV-229E, NL63, OC43 and HKU1, see Dangi et al., 2025, J Virol, 0:e01526-25) and Montesinos-Guevara et al. (Cochraine Database of Systematic Reviews, 2022, Issue 12, Art. No. CD002190, see page 6). As for SARS-CoV (SARS-CoV-1), there is no recognized vaccine or treatment with a vaccine (see Abdolmaleki et al. (Daru, 2022, 30(2):379-406), page 400, Conclusion). With regard to MERS, there is promising development, but with a very different construct, an MVA vector expressing S (see Raadsent et al., The Lancet Infectious Diseases, 2025, 25(2):231-242). Lastly, treatment of COVID-19 with a vaccine is not an option, rather, antiviral drugs (see CDC’s Types of COVID-19 Treatment, accessed on 11/18/2025 from www.cdc.gov/covid/treatment/index.html, 4 pages).
Given the breadth of the claims, the nature of the invention, the state of the art, the limited guidance and working examples in the specification, and the low level of predictability, it would require undue experimentation to make and use the claimed vaccines and methods of prevention and treatment.
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.
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 1, 4, 6 and 9-20 are rejected under 35 U.S.C. 103 as being unpatentable over Qi et al. (Chem. Comm., published June 23, 2020, 56, 8683, four pages, “Qi”) in view of Dutta et al. (Journal of Virology, July 2020, 94(13):e000647-20, two pages, “Dutta”) and Rice et al. (bioRxiv 2020.07.29.227595, July 2020, “Rice”). The claims are summarized above and correlated with the teachings of the prior art in bold font below. The claims are rejected on the basis of their enabled embodiments (i.e., immunogenic compositions and methods of inducing an immune response, where applicable).
Qi discloses a fusion protein comprising a mouse IgG Fc and a SARS-CoV-2 RBD of the S protein, wherein the Fc is fused to the C-terminus of the RBD (see abstract and Figure 1) (claim 1, aspects of fusion protein comprising coronavirus RBD and IgG Fc domain, and claims 4, 6 and 9). The fusion protein was produced from a plasmid vector in a host cell (see second page, bridging paragraph between left and right columns) (claims 15-18). Qi suggests that the composition be further developed as a vaccine for COVID-19 (see abstract) (claims 10, 13, 14, 19 and 20). Adjuvants were also used, including alum (see second page, right column, first full paragraph) (claims 11 and 12).
Dutta discloses SARS-CoV N protein as immunogenic, and suggests SARS-CoV-2 N protein as a target for vaccine development for COVID-19 (see page 1). It would have been obvious to have incorporated the N protein into the RBD-Fc fusion protein of Qi. One would have been motivated to include the N protein in order to increase the immunogenicity of the fusion protein, with a reasonable expectation of success, given that Dutta teaches that SARS-CoV N protein is immunogenic. Rice also confirms that SARS-CoV N protein is known to be immunogenic, and suggests the use of the SARS-CoV-2 N protein in a single construct comprising SARS-CoV-2 RBD and N protein, albeit, in a different vector construct (see Rice, page 4, second full paragraph, and Figure 1h) (claim 1, aspect of N protein). Therefore, the claimed embodiments would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over Qi et al. (Chem. Comm., published June 23, 2020, 56, 8683, four pages, “Qi”) in view of Dutta et al. (Journal of Virology, July 2020, 94(13):e000647-20, two pages, “Dutta”) and Rice et al. (bioRxiv 2020.07.29.227595, July 2020, “Rice”), as applied to claim 1 above, and further in view of GenBank Accession No. QHD43416.1 (March 18, 2020, accessed on 11/17/2025 from www.ncbi.nlm.nih.gov/protein/1791269090). Claim 2 is directed to an embodiment wherein the sequence of the RBD comprises SEQ ID NO: 1, which represents a portion of SARS-CoV-2 RBD.
The teachings of Qi, Dutta and Rice are outlined above, none of which disclose Applicant’s SEQ ID NO: 1 as the RBD sequence. However, it would have been obvious to have used any known RBD sequence in the art, with a reasonable expectation of success, such as the RBD of the sequence QHD43416.1, amino acids 319-541, an identical match for Applicant’s SEQ ID NO: 1. Therefore, the claimed embodiment would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Qi et al. (Chem. Comm., published June 23, 2020, 56, 8683, four pages, “Qi”) in view of Dutta et al. (Journal of Virology, July 2020, 94(13):e000647-20, two pages, “Dutta”) and Rice et al. (bioRxiv 2020.07.29.227595, July 2020, “Rice”) as applied to claim 1 above, and further in view of GenBank Accession No. YP_009724397.2 (July 18, 2020, accessed on 11/17/2025 from www.ncbi.nlm.nih.gov/protein/1798174255). Claim 3 is directed to an embodiment wherein the sequence of the N protein comprises SEQ ID NO: 4, which represents a portion of SARS-CoV-2 N.
The teachings of Qi, Dutta and Rice are outlined above, none of which disclose Applicant’s SEQ ID NO: 4 as the N protein. However, it would have been obvious to have used any known N sequence in the art, with a reasonable expectation of success, such as the N sequence of YP_009724397.2 is amino acids 36-191, an identical match for Applicant’s SEQ ID NO: 4. Therefore, the claimed embodiment would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Claims 5, 7 and 8 are rejected under 35 U.S.C. 103 as being unpatentable over Qi et al. (Chem. Comm., published June 23, 2020, 56, 8683, four pages, “Qi”) in view of Dutta et al. (Journal of Virology, July 2020, 94(13):e000647-20, two pages, “Dutta”) and Rice et al. (bioRxiv 2020.07.29.227595, July 2020, “Rice”), and further in view of Super et al. (US Patent 9,988,617, “Super”). Claim 5 is directed to an embodiment wherein the sequence of the Fc comprises SEQ ID NO: 2. Claim 7 is directed to an embodiment wherein the RBD and N are linked to the Fc at opposite ends. Claim 8 is directed to an embodiment wherein the fusion protein is a dimer of an Fc domain to which the RBD and N are linked.
The teachings of Qi, Dutta and Rice are outlined above, none of which disclose Applicant’s SEQ ID NO: 2 as the Fc protein. However, it would have been obvious to have claimed any known Fc sequence, such as Super’s SEQ ID NO: 35, an exact match for Applicant’s SEQ ID NO: 2.
Qi’s teachings are outlined above. With regard to the Fc domain, Qi uses an Fc domain, which is naturally a dimer (see Qi, page 3, left column, first full paragraph) (claim 8, aspect of Fc dimer). It would have been obvious to have arranged the RBD, N and Fc portions such that each of RBD and N are on opposite ends of the Fc. Super teaches that Fc regions have multiple advantageous uses in fusion proteins, such as facilitating expression and purification, increasing molecular weight of a fusion protein to help avoid glomerular filtration, and allowing dimerization (see col. 6, lines 38-54). One would have been motivated to construct a dimer, in the sense that RBD and N are on either ends of the Fc, thus allowing for each of RBD and N to be exposed to the immune system without interference from the other, allowing for greater immunogenicity. Therefore, the claimed embodiments would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
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, 4 and 6-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 9 and 11-26 of copending Application No. 18/044,365 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other. The instant claims are outlined above. The copending claims are directed to a fusion protein comprising coronavirus-derived RBD variant having reduced binding affinity to an ACE2 receptor and a SARS-CoV-2 N protein (copending claim 9), and also an Fc domain (claim 11). None of the copending claims are directed to a fusion protein comprising the RBD, N and Fc, however, it would have been obvious to have claimed all three together in a fusion protein, since the combination of RBD and N is claimed (copending claim 9), and the combination of RBD and Fc is claimed (copending claim 11). As for the other embodiments of IgG Fc, location of links, adjuvants, nucleic acids, vectors, host cells and methods of vaccination, prevention and treatment, these are found throughout copending claims 13-26. The copending claims are not directed to methods of producing a fusion protein, however, copending claim 26 is directed to a host cell into which a nucleic acid construct is introduced. Since host cells express the nucleic acid, a method of production would have been obvious to claim. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 2 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 9 and 11-26 of copending Application No. 18/044,365 (reference application), as applied to claim 1 above, and further in view of GenBank Accession No. QHD43416.1 (March 18, 2020, accessed on 11/17/2025 from www.ncbi.nlm.nih.gov/protein/1791269090).
Although the claims at issue are not identical, they are not patentably distinct from each other. Claim 2 is directed to an embodiment wherein the sequence of the RBD comprises SEQ ID NO: 1, which represents a portion of SARS-CoV-2 RBD. It would have been obvious to have used any known RBD sequence in the art, with a reasonable expectation of success, such as the RBD of the sequence QHD43416.1, amino acids 319-541, an identical match for Applicant’s SEQ ID NO: 1. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 3 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 9 and 11-26 of copending Application No. 18/044,365 (reference application), as applied to claim 1 above, and further in view of GenBank Accession No. YP_009724397.2 (July 18, 2020, accessed on 11/17/2025 from www.ncbi.nlm.nih.gov/protein/1798174255).
Although the claims at issue are not identical, they are not patentably distinct from each other. Claim 3 is directed to an embodiment wherein the sequence of the N protein comprises SEQ ID NO: 4, which represents a portion of SARS-CoV-2 N. It would have been obvious to have used any known N sequence in the art, with a reasonable expectation of success, such as the N sequence of YP_009724397.2 is amino acids 36-191, an identical match for Applicant’s SEQ ID NO: 4. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 5 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 9 and 11-26 of copending Application No. 18/044,365 (reference application), as applied to claim 1 above, and further in view of Super et al. (US Patent 9,988,617, “Super”).
Although the claims at issue are not identical, they are not patentably distinct from each other. Claim 5 is directed to an embodiment wherein the sequence of the Fc comprises SEQ ID NO: 2. It would have been obvious to have claimed any known Fc sequence, such as Super’s SEQ ID NO: 35, an exact match for Applicant’s SEQ ID NO: 2. Super teaches that Fc regions have multiple advantageous uses in fusion proteins, such as facilitating expression and purification, increasing molecular weight of a fusion protein to help avoid glomerular filtration, and allowing dimerization (see col. 6, lines 38-54). This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claim is allowed.
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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