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 .
Applicant’s preliminary amendment filed on October 20, 2023 is acknowledged. Claims 1-14 and 17-22 are pending and under examination in this Office action.
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.
Claims 1-14 and 17-22 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.
Claims are drawn to a nucleic acid molecule encoding a glycan-coated immunogen modified to encode at least one non-native site for glycan modification, a nanoparticle comprising a nucleic acid molecule encoding a glycan-coated immunogen and a method of inducing an immune response against SARS-CoV-2 in a subject in need thereof, the method comprising administering a nucleic
Claims are rejected because of lack of structure and function correlation between the claimed genus of glycan-coated immunogens modified to encode at least one non-native site for glycan modification and the function of a vaccine producing anti-coronavirus antibody.
Applicant’s specification discloses a nanoparticle wherein the nucleic acid molecule comprises a nucleotide sequence selected from the group consisting of: (a) the nucleotide sequence having at least about 90% identity over an entire length of the nucleic acid sequence selected from the group consisting of SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO: 7, SEQ ID NO:9, SEQ ID NO: 11, SEQ ID NO: 13, SEQ ID NO: 15, SEQ ID NO:17, SEQ ID NO: 19, SEQ ID NO:21, SEQ ID NO:23, SEQ ID NO:25, SEQ ID NO:27, SEQ ID NO:29, SEQ ID NO:31, SEQ ID NO:33, SEQ ID NO:35, SEQ ID NO:37, SEQ ID NO:39, SEQ ID NO:41, SEQ ID NO:43, SEQ ID NO:45, SEQ ID NO:47, SEQ ID NO:49, SEQ ID NO:51, SEQ ID NO:53, SEQ ID NO:55, SEQ ID NO:57, SEQ ID NO:59, SEQ ID NO:61, SEQ ID NO:63, SEQ ID NO:65, SEQ ID NO:67, SEQ ID NO:69, SEQ ID NO:71, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:77, SEQ ID NO:79, SEQ ID NO:81, SEQ ID NO:83, SEQ ID NO:85, SEQ ID NO: 87, SEQ ID NO: 89, SEQ ID NO:91, SEQ ID NO:93, SEQ ID NO:95, SEQ ID NO:97, SEQ ID NO:99, SEQ ID NO: 101, and SEQ ID NO: 103; and the nucleic acid sequence selected from the group consisting of SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO: 13, SEQ ID NO: 15, SEQ ID NO: 17, SEQ ID NO: 19, SEQ ID NO:21, SEQ ID NO:23, SEQ ID NO:25, SEQ ID NO:27, SEQ ID NO:29, SEQ ID NO:31, SEQ ID NO:33, SEQ ID NO:35, SEQ ID NO:37, SEQ ID NO:39, SEQ ID NO:41, SEQ ID NO:43, SEQ ID NO:45, SEQ ID NO:47, SEQ ID NO:49, SEQ ID NO:51, SEQ ID NO:53, SEQ ID NO:55, SEQ ID NO:57, SEQ ID NO:59, SEQ ID NO:61, SEQ ID NO: 63, SEQ ID NO:65, SEQ ID NO: 67, SEQ ID NO:69, SEQ ID NO:71, SEQ ID NO:74, SEQ ID NO: 75, SEQ ID NO: 77, SEQ ID NO: 79, SEQ ID NO:81, SEQ ID NO:83, SEQ ID NO:85, SEQ ID NO:87, SEQ ID NO:89, SEQ ID NO:91, SEQ ID NO:93, SEQ ID NO:95, SEQ ID NO:97, SEQ ID NO:99, SEQ ID NO: 101, and SEQ ID NO: 103.
Applicant’s specification fails to provide an adequate number of species representing the claimed genus modified glycan-coated immunogens. The SEQ ID NOs representing the amino acid sequences as well as nucleic acid sequences do not contain the claimed non-native site for glycan modification. Therefore claims 12 and 13 are rejected although they recite specific SEQ ID NOs.
Applicant’s claims recite one non-native site for glycan modification. There is a lack of structure with regard to the one non-native site.
Wang et al., (Nature, 2026, Vol. 11:117, p. 1-13) disclose effects of glycosylation sites on the immunogenicity of COVID-19 vaccines and disclose N343 glycosylation hot spot. Based on the teachings in Wang et al. the skilled artisan would conclude that glycosylation of only specific residues within SARS-CoV-2 S protein would contribute to the enhanced effect of immunogenicity. The present claims broadly encompass a large genus of modifications and do not expressly recite which specific nucleotides are glycosylated.
Thus, in view of the above, the present claims are rejected for lack of written description support.
Claim Rejections - 35 USC § 102
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 1-14 and 17-22 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Joyce et al. (US Patent Application Publication US 2023/0285539).
Joyce discloses a polypeptide sequence 90% identical with present SEQ ID NO: 12 (see SEQ ID NO: 31 and a sequence alignment below) Joyce discloses A nanoparticle comprising a fusion protein comprising a nanoparticle-forming peptide and at least one antigenic coronavirus peptide selected from: a. a receptor-binding domain (RBD) of a coronavirus, or a fragment or variant thereof, b. an N-terminal domain (NTD) of a coronavirus, or a fragment or variant thereof, c. an S1 domain of a coronavirus, or a fragment or variant thereof, d. a stabilized extracellular spike S-2P domain of a coronavirus, or a fragment or variant thereof, e. a stabilized extracellular spike S domain of a coronavirus, or a fragment or variant thereof, or f. a stabilized extracellular spike S-trimer of a coronavirus, or a fragment or variant thereof,.
Joyce discloses in FIG. 5 SARS-CoV-2 RBD-Ferritin variants with increased nanoparticle formation, stability, and yield. Panel (A) shows the crystal structure of SARS-CoV-2 RBD and Panels (B-G) show variants comprising select amino acid modifications. Alterations to less hydrophobic residues or introduction of glycans at these residues will serve to increase nanoparticle yield, formation and stability. Panels (H-N) show variants comprising select amino acid modifications. Alterations to less hydrophobic residues or introduction of glycans at these residues will serve to increase nanoparticle yield, formation, and stability. Native residues shown in sphere representation.
Present SEQ ID NO: 12 and SEQ ID NO: 31 in Joyce
Query Match 90.2%; Score 1808; Length 414;
Best Local Similarity 95.1%;
Matches 348; Conservative 2; Mismatches 10; Indels 6; Gaps 1;
Qy 19 MQIYEGKLTAEGLRFGIVASRANHALVDRLVEGAIDAIVRHGGREEDITLVRVCGSWEIP 78
||||||||||||||||||||| ||||||||||||||||||||||||||||||| ||||||
Db 1 MQIYEGKLTAEGLRFGIVASRFNHALVDRLVEGAIDAIVRHGGREEDITLVRVPGSWEIP 60
Qy 79 VAAGELARKEDIDAVIAIGVLCRGATPSFDYIASEVSKGLADLSLELRKPITFGVITADT 138
||||||||||||||||||||| ||||| ||||||||||||||||||||||||||||||||
Db 61 VAAGELARKEDIDAVIAIGVLIRGATPHFDYIASEVSKGLADLSLELRKPITFGVITADT 120
Qy 139 LEQAIEAAGTCHGNKGWEAALCAIEMANLFKSLR------GGSGGSGGGNITNLCPFGEV 192
|||||| ||| |||||||||| |||||||||||| ||||||||||||||||||||
Db 121 LEQAIERAGTKHGNKGWEAALSAIEMANLFKSLRGGSGGSGGSGGSGGGNITNLCPFGEV 180
Qy 193 FNATRFASVYAWNRTRISNCVADYSVLYNSASFSTFKCYGVNPTKLNDLCFTNVYADSFV 252
|||||||||||||| ||||||||||||||||||||||||||:||||||||||||||||||
Db 181 FNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFV 240
Qy 253 IRGDEVRQIAPGQTGKIADYNYKLPDNFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNL 312
||||||||||||||||||||||||||:|||||||||||||||||||||||||||||||||
Db 241 IRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNL 300
Qy 313 SPFERDISTEIYQAGSTPCNGTEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAP 372
|||||||||||||||||||| ||||||||||||||||||||||||||||||||||||||
Db 301 KPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAP 360
Qy 373 ATVCGP 378
||||||
Db 361 ATVCGP 366
Claims 1-11, 14 and 17-22 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Ying et al. (US Patent US 11,510,977).
Ying et al. disclose a polypeptide representing SARS-CoV-2 S protein and the RBD domain modified to attach sugar residues, methods of producing antibodies comprising administering SARS-CoV-2 S protein and the RBD domain modified to attach sugar residues, (see SEQ ID NO: 59 in Ying et al. and the sequence alignment below, claims 1-23, column 18, lines 22-31, column 77, lines 20-67, column 78, lines column 79, lines 46-67, column 182, lines 22-65, Figures 5 and 7, Example 1-7).
Ying et al. disclose RBD comprising one or more amino acid substitutions in the RBD that are capable of increasing binding affinity of the RBD to receptor in a host cell. In some embodiments, the receptor is ACE2. In some embodiments, the amino acid substitution comprises N501T (see column 44).
Thus, by this disclosure Ying et al., anticipate the present claims.
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 17-22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 11-21, 23, 25, 27-31 of copending Application No. 18/251,620 in view of Chen et al. (bioRXIV, December 1, 2020).
Present claims are drawn to A nucleic acid molecule encoding a glycan-coated immunogen modified to encode at least one non-native site for glycan modification, wherein the nucleic acid molecule comprises a nucleotide sequence selected from the group consisting of:
the nucleotide sequence encodes a peptide comprising an amino acid sequence having at least about 90% identity over an entire length of an amino acid sequence selected from the group consisting of SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:20, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:26, SEQ ID NO:28, SEQ ID NO:30, SEQ ID NO:32, SEQ ID NO:34, SEQ ID NO:36, SEQ ID NO:38, SEQ ID NO:40, SEQ ID NO:42, SEQ ID NO:44, SEQ ID NO:46, SEQ ID NO:48, SEQ ID NO:50, SEQ ID NO:52, SEQ ID NO:54, SEQ ID NO:56, SEQ ID NO:58, SEQ ID NO:60, SEQ ID NO:62, SEQ ID NO:64, SEQ ID NO:66, SEQ ID NO:68, SEQ ID NO:70, SEQ ID NO:72, SEQ ID NO:74, SEQ ID NO:76, SEQ ID NO:78, SEQ ID NO:80, SEQ ID NO:82, SEQ ID NO:84, SEQ ID NO:86, SEQ ID NO:88, SEQ ID NO:90, SEQ ID NO:92, SEQ ID NO:94, SEQ ID NO:96, SEQ ID NO:98, SEQ ID NO:100, SEQ ID NO:102, and SEQ ID NO:104; and the nucleotide sequence encodes a peptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:20, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:26, SEQ ID NO:28, SEQ ID NO:30, SEQ ID NO:32.
The claims of the copending application 18/251,620 are drawn to A nucleic acid molecule comprising a nucleotide sequence encoding a SARS-CoV-2 spike protein receptor binding domain (RBD), wherein the nucleic acid molecule comprises a nucleotide sequence selected from the group consisting of:
(a) the nucleotide sequence encodes a peptide comprising an amino acid sequence having at least about 90% identity over an entire length of an amino acid sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6 and SEQ ID NO:8;
(b) the nucleotide sequence encodes a peptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6 and SEQ ID NO:8;
(c) the nucleotide sequence encodes at least two peptides, wherein each of the at least two peptides comprises an amino acid sequence having at least about 90% identity over an entire length of an amino acid sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6 and SEQ ID NO:8; and
(d) the nucleotide sequence encodes at least two peptides, wherein each of the at least two peptides comprises an amino acid sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6 and SEQ ID NO:8.
The present claims and the claims of the copending application are drawn to the same nucleic acid sequences encoding the same amino acid sequences. The only difference between the present claims and the claims of the copending application is that the claims of the present application require the glycan modification.
It is the Examiner’s position that attaching N glycosylation sites would have been obvious in view of the teachings of Chen et al.
Chen et al., teach N glycosylation of multiple residues within SARS-CoV-2 S protein and glycan binding ability of SARS-CoV-2 S protein (see the entire document, particularly paragraph 3.3).
It would have been prima facie obvious to modify presently claimed nucleic acids as suggested by Chen et al. and to add N-glycosylation sites, because Chen et al. teach that the glycosylation of SARS-CoV-2 facilitates the infection of host cells (see under paragraph 3.3).
Thus, the present claims would have been prima facie obvious at the time the invention was made.
This is a provisional nonstatutory double patenting rejection.
Pertinent references
Chen et al. (bioRXIV, December 1, 2020) teach N glycosylation of multiple residues within SARS-CoV-2 S protein and glycan binding ability of SARS-CoV-2 S protein (see the entire document, particularly paragraph 3.3). Chen et al. teach that the glycosylation of SARS-CoV-2 facilitates the infection of host cells (see under paragraph 3.3).
Contact Information
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/AGNIESZKA BOESEN/Primary Examiner, Art Unit 1648
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