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 .
Election Restrictions
Applicant’s election without traverse of Group I, claims 1, 2, 5-12, 15-18, 21 and 22, drawn to an immunogenic composition and the species of SEQ ID NO: 15, in the reply filed on 10/31/2025 is acknowledged.
It is noted that Applicant’s elected species of SEQ ID NO:15 comprises a polynucleotide 3822 base pairs long which encodes the complete SARS-CoV-2 spike protein (Specification, Table 3). Instant claim 9 recites “an accessory protein of a coronavirus” and therefore it is considered to be outside the scope of instant claims for the following reasons: as indicated in the Restriction Action issued 08/01/2025, the species are independent or distinct because: sequences encoding different proteins are structurally distinct chemical compounds and are unrelated to one another. These sequences are thus deemed to constitute independent and distinct inventions within the meaning of 35 U.S.C. § 121. Absent evidence to the contrary, each such nucleotide sequence is presumed to represent an independent and distinct invention, subject to a restriction requirement pursuant to 35 U.S.C. § 121 and 37 CFR 1.141 et seq. (MPEP § 803.04). Accordingly, claim 9 is withdrawn from consideration as being directed to a non-elected species. See 37 CFR 1.142(b) and MPEP § 821.03.
Claims 9, 24, 25, 28, 31 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Invention, there being no allowable generic or linking claim.
Claims 1, 2, 5-8, 10-12, 15-18, 21 and 22 are under examination on the merits.
Priority
Applicant’s claim for domestic benefit of prior-filed provisional applications No. 63/125,778 filed on 12/15/2020, 63/074,442 filed on 09/03/2020, 63/068,936 filed 08/21/2020, 63/034,704 filed on 06/04/2020, 63/027,932 filed on 05/20/2020 under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged.
Information Disclosure Statement
The information disclosure statement (IDS) was submitted on 08/14/2023, 03/14/2025, 10/31/25. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code, for example in page 87. 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.
The use of the term “Tween” for example on pages 103, 113, etc. 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.
Note that “Tween” is merely an example and all improper uses of trademarks in the specification should be identified by Applicant and properly addressed.
It is noted that the Specification is missing a paragraph indicating cross-references to related applications.
Claim Objections
Claims 1, 2, 7, and 21 are objected to because of the following informalities:
On claim 1, the recitation of “the coronavirus antigen is from severe acute…” should read “the coronavirus antigen is from a severe acute…”. Appropriate correction is required.
On claim 2, the recitation of “17 19” is missing a comma between the two numbers. It should read “17, 19”. Appropriate correction is required.
On claim 7, the recitation of “a receptor binding domain of spike protein…” should read “a receptor binding domain of a spike protein…”. Appropriate correction is required.
On claim 21, the recitation of “SEQ ID NOs: 13, 15, and 12” should be in numerical order “SEQ ID NOs: 12, 13, and 15”. Appropriate correction is required.
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 1, 2, 5-8, 10-12, 15-18, 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.
Claim 1 recites “the coronavirus antigen is from severe acute respiratory syndrome (SARS)-related coronavirus or a fragment thereof.” It is not clear what is encompassed by the term ‘SARS-related coronavirus’ because the term is not defined by the claim and the Specification does not provide a standard for ascertaining the requisite degree. In other words, it is not clear to what degree must an antigen be homologous (share a common evolutionary ancestor) to a SARS coronavirus, or what level of similarity (structural and/or functional) must an antigen have, to be considered “related” to SARS coronavirus. Therefore, one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The dependent claims do not provide additional clarity. Therefore, the claims are indefinite. For purposes of compact prosecution and applying prior art, claim 1 was interpreted herein as referring to the coronavirus antigen from a severe acute respiratory syndrome (SARS) coronavirus or a fragment thereof.
It is noted that any interpretation of the claims set forth above does not relieve Applicant of the responsibility of responding to this Office Action. If the actual interpretation of the claims is different than that posited by the Examiner, additional rejections and art may be readily applied in a subsequent final Office Action.
Claim Rejections - 35 USC § 112 - Written Description
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 1, 2, 5-8, 10-12, 15-18, and 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
See claims 1, 2, 5-8, 10-12, 15-18, and 22 as submitted on 10/31/2025.
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the inventor was in possession of the claimed genus. See, e.g., Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1340, 94 USPQ2d 1161, 1167 (Fed. Cir. 2010); University of California v. Eli Lilly & Co., 119 F.3d 1559, 43 USPQ2d 1398 (Fed. Cir. 1997) at 1406; Juno Therapeutics, Inc. v. Kite Pharma, Inc., 10 F.4th 1330, 1337, 2021 USPQ2d 893 (Fed. Cir. 2021) ("[T]he written description must lead a person of ordinary skill in the art to understand that the inventor possessed the entire scope of the claimed invention. Ariad, 598 F.3d at 1353–54 ('[T]he purpose of the written description requirement is to ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor's contribution to the field of art as described in the patent specification.' (internal quotation marks omitted).").
A “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014). The issue is whether the skilled artisan would understand inventor to have invented, and been in possession of, the invention as claimed.
The Federal Circuit has clarified the application of the written description requirement to inventions in the field of biotechnology. See University of California v. Eli Lilly and Co., 119 F.3d 1559, 1568,43 USPQ2d l398, 1406 (Fed. Cir. 1997). The Court stated that a written description of an invention requires a precise definition, one that defines the structural features of the chemical genus that distinguishes it from other chemical structures. A definition by function does not suffice to define the genus because it is only an indication of what the genus does, rather than what it is. Further, the Court held that to adequately describe a claimed genus, an applicant must describe a representative number of species of the claimed genus, and that one of skill in the art should be able to “visualize or recognize the identity of the members of the genus.”
The instant claims require a circular polyribonucleotide comprising a sequence encoding a coronavirus antigen, and having immunogenic properties. The instant claims alternatively require a circular polyribonucleotide or fragment thereof wherein sequence alterations such as substitutions, additions, insertions, or deletions of one or more amino acids can be made anywhere in the amino acid sequences or fragments thereof of for example, SEQ ID NO: 15 (Applicant’s elected species), including within specific regions essential for transmembrane anchoring, receptor binding, membrane fusion, etc., provided that a circular polyribonucleotide bears at least 80% sequence homology to for example, SEQ ID NO: 15 (Applicant’s elected species). It is noted that instant SEQ ID NO:15 (Applicant’s elected species) comprises a polynucleotide 3822 base pairs long and it encodes the complete SARS-CoV-2 spike protein, including the transmembrane domain fully intact (Specification Table 3). It should also be noted that aberrant gene expression can arise from gene sequence alterations or alterations in an RNA transcript. Finally, the instant claims alternatively require a linear polyribonucleotide comprising sequences encoding two or more antigens, wherein at least one antigen is a coronavirus sequence of for example SEQ ID NO: 15 (Applicant’s elected species) (claim 22), and having immunogenic properties. Accordingly, it is noted that the instant claims encompass both circular and linear polyribonucleotides. However, the Specification has failed to sufficiently describe the structural features that must be retained by members of the claimed genus as to establish a structure-function relationship with respect to immunogenic properties.
As indicated above, SEQ ID NO: 15, e.g., is 3822 base pairs long. The instant claims encompass any sequence having at least 80% sequence identity to SEQ ID NO: 15. A polynucleotide sequence sharing only 80% identity relative to SEQ ID NO: 15 could have anywhere from 1 to 764 substitutions, deletions, or additions in any combination along any length of SEQ ID NO: 15, which corresponds to a massive genus (4764 = 1.26 x 10645) comprising trillions upon trillions of sequences, with respect to SEQ ID NO: 15 alone. However, while the claims are drawn to a genus that comprises innumerable sequences, the Specification has only adequately described and successfully reduced to practice the full-length of SEQ ID NO: 15. This is not representative of the extremely large genus of sequences claimed, since no variants, mutants, etc. of SEQ ID NO: 15 are demonstrated to have immunogenic properties.
At best, the Specification contemplates the use of BLAST to identify functional homologs based on sequence homology. However, this is not sufficient to describe members of the claimed genus because such methods access online databases that are continually being updated as sequencing technology improves. As a result, they are not a static source of information. Thus, one of skill in the art would readily appreciate that relying on a non-patent source that is continuously subject to change as a means to identify members of the claimed genus does not sufficiently meet the written description requirement.
Moreover, with respect to nucleic acid sequences encoding amino acid sequences required for protein expression, Friedberg (“Automated protein function prediction--the genomic challenge”. Brief Bioinform. 2006;7(3):225-242.) teaches that homology-based transfer is not reliable for functional annotation even with high alignment percentages (page 227, second column). Friedberg also teaches that identification of functionally significant sub-regions is critical to functional annotation, and that often addition, deletion, or re-shuffling of domains can lead to errors in annotation (page 227, second column; page 228, first paragraph). Furthermore, Friedberg teaches that sequence-based tools are just not sensitive enough to identify functional protein similarity as databases get larger, and diversity of sequences gets larger (page 228, first full paragraph).
Thorton (“Structural genomics takes off.” Trends Biochem Sci. 2001;26(2):88-89.) teaches that the same protein structure is often seen in apparently different homologous families with different functions. Thorton further describes examples of little correlation between specific binding function and overall protein structure (page 992, right column, at lines 2-10). Thus, when taken with the teachings of Friedberg and Thorton, one of skill in the art would readily appreciate that sequence homology alone cannot serve as the basis to describe members of the genus that have the recited function.
In the absence of a representative number of examples, the Specification must at least describe the structural features that are required for the claimed function, in this case immunogenic properties and function. However, as discussed above, the Specification fails to describe any substantive structural limitations as to establish a structure-function relationship with respect to immunogenic properties and function.
Accordingly, the claims as currently written are not adequately described and one of skill in the art would readily appreciate that Applicant was not in possession of the claimed genus at the time of filing.
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 1, 2, 5-12, 15-18, 21 and 22 are rejected under 35 U.S.C. 103 as being unpatentable over U.S. patent No. 5,766,903 to Sarnow et al. dated 06/16/1998, in view of PGPub US 2021/0353741 A1 to Anderson et al. effectively filed on 03/30/2020 (See PTO-892: Notice of References Cited)
See claims 1, 2, 5-8, 10-12, 15-18, 21 and 22 as submitted on 10/31/2025.
Regarding claim 1, Sarnow et al. teach immunogenic compositions comprising circular RNAs, wherein the circular RNAs are related to the DNA sequence from which the circular RNAs derive and the circular RNA encodes an antigen (Abstract, columns 5 and 6). Sarnow et al. further teach that such circular RNAs enable production of large amounts of desired polypeptides, particularly eukaryotic polypeptides (column 1).
Sarnow et al. do not teach and circular RNA sequence comprising a sequence encoding a coronavirus antigen, wherein the coronavirus antigen is from a SARS coronavirus.
However, Anderson et al. teach immunogenic compositions comprising an antigen, wherein the antigen is a SARS-CoV-2 spike protein (Abstract, ¶¶ [0028-0032]). Anderson et al. further teach a 3822 bp long sequence comprising a complete RNA sequence encoding the SARS-CoV-2 spike protein (SEQ ID NO: 20).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to have incorporated the RNA sequence as taught by Anderson et al. into the immunogenic composition of Sarnow et al. for the benefit of formulating an immunogenic composition comprising circular RNAs to enable production of large amounts of a SARS-CoV-2 spike protein, particularly in eukaryotic systems. See MPEP 2144.07. The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945).
One of ordinary skill in the art would have had reasonable expectation of success in incorporating the RNA sequence as taught by Anderson et al. into the immunogenic composition of Sarnow et al. given that the methods of formulating circular RNAs for expression of antigens are well known, successfully demonstrated, and commonly used as evidenced by the applied prior art.
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Regarding claim 2 the RNA sequence taught by Anderson et al. referred to above shares 99.7% sequence identity with instant SEQ ID NO: 15, see alignment below (Qy is instant SEQ ID NO: 15; Db is Anderson et al.’s SEQ ID NO: 20). Note that the alignment below only shows the first ~500 base pairs, however both sequences are 3822 pb long.
Regarding claims 5-8, as indicated above, Anderson et al. teach immunogenic compositions comprising an antigen, wherein the antigen is a SARS-CoV-2 spike protein (Abstract, ¶¶ [0028-0032]), wherein the spike protein lacks a cleavage site (¶ [0052]).
Regarding claims 10-12, 15-17, 18 Sarnow et al. teach circular polyribonucleotides encoding two or more antigens (i.e. at least two or three), wherein the antigens comprise open reading frames (ORFs) encoding antigens for gene expression, and wherein the antigens are from two or more different organisms (viruses, parasites or bacteria) (columns 6, 7, 14). As explained above, Anderson et al. teach an antigen comprising an RNA sequence encoding the SARS-CoV-2 spike protein (Abstract, ¶¶ [0028-0032]).
Regarding claims 21 and 22, Sarnow et al. further teach immunogenic compositions comprising multiple (two or more) linear polyribonucleotide sequences (columns 6, 7, 14). As explained above, Anderson et al. teach a polynucleotide sequence encoding a SARS-CoV-2 spike protein antigen (Abstract, ¶¶ [0028-0032], [0055]). It is noted that claim 21 recites “comprising a sequence of SEQ ID NO: 15”. Here, under BRI, the claim is interpreted as comprising any amino acid sequence of any length that matches a portion of SEQ ID NO: 15. The sequence taught by Anderson et al. is linear (SEQ ID NO: 20) and shares 99.7% sequence identity with instant SEQ ID NO:15 (see alignment above). The teachings of Sarnow et al. and Anderson et al. in combination teach the limitations of claims 21 and 22.
Accordingly, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date, especially in the absence of evidence to the contrary.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARLENE V BUCKMASTER whose telephone number is (703)756-5371. The examiner can normally be reached M-F 8-5.
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/MARLENE V BUCKMASTER/Examiner, Art Unit 1672
/THOMAS J. VISONE/Supervisory Patent Examiner, Art Unit 1672