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 inventive Group II in the reply filed on 12/5/25 is acknowledged. The claims of invention I have been cancelled in applicant’s reply of 12/5/25.
Claims 20, 21 and 25-42 are examined on the merits. Claims 25-42 are newly presented.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 7/13/23 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Drawings
The drawings are objected to because the text of figures 2 and 7A are unclear. 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.
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.
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 39-41 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 inventories), at the time the application -was filed, had possession of the claimed invention.
The following quotation from section 2163 of the Manual of Patent Examination Procedure is a brief discussion of what is required in a specification to satisfy the 35 U.S.C. 112 written description requirements for a generic claim covering several distinct inventions:
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 applicant was in possession of the claimed genus... See BU Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
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.
Thus, when a claim covers a genus of inventions, the specification must provide written description support for the entire scope of the genus. Support for a genus is generally found where the applicant has provided a number of examples sufficient so that one in the art would recognize from the specification the scope of what is being claimed.
Claims 39-41 are rejected as lacking adequate descriptive support for an assay that employs a test agent that is an antibody, such as one from a subject previously infected with a non-Omicron SARS-CoV-2 or is obtained from a vaccinated subject.
The claimed invention requires: an assay for SARS-CoV-2 replication comprising:
contacting a cultured cell expressing or containing a recombinant SARS-CoV-2 nucleic acid segment encoding a heterologous S protein and a reporter protein replacing an ORF7a encoding segment forming a test cell;
contacting the test cell with a test agent; and
assessing the replication of the recombinant SARS-CoV-2 nucleic acid segment in the presence of the test agent.”
Applicants tested the ability of a test agent (serum collected from naturally infected patients or those receiving a Moderna SARS-CoV-2 vaccine) to inhibit the infection of Vero E6 cells by a SARS-CoV-2 virus that possesses a heterologous spike protein (and genetic sequence) along with a mNeonGreen (mNG) reporter protein, that is expressed by a gene inserted in place of the ORF7a gene.
In support of the claimed genus of a “a test agent (an antibody) that would interact with the cultured cell in order to assess the replication of the recombinant SARS-CoV-2 nucleic acid segment” applicants employed serum collected from humans. More specifically, applicants tested the ability of a test agent (serum collected from human patients receiving a Pfizer or Moderna SARS-CoV-2 vaccine) to inhibit the infection of Vero E6 cells by a SARS-CoV-2 virus that possesses a heterologous spike protein (and genetic sequence) along with a mNeonGreen (mNG) reporter protein, that is expressed by a gene inserted in place of the ORF7a gene. However, the serum employed by applicant is a mixture of monoclonal antibodies, while the test agent claimed is an antibody.
Moreover, the decision arrived at in Amgen v. Sanofi (598 U.S. 2023) supports expanded analysis of whether a claim drawn to an antibody being specific for an epitope, even a specific epitope, permits an applicant to pursue all possible antibodies that are capable of being produced against such an epitope. Presently, the claimed test agent (antibody) is only defined by functional properties but no specific structure is recited by the claims. For example, the antibody is obtained from a subject previously infected with a non-Omicron SARS-CoV-2 or being previously vaccinated. However the claims nor the specification provide any structure (i.e., 6 complementaory determining regions (CDRs)), variable domains or full-length sequences) of the antibod(ies) employed as a test agent. As stated above, applicants do test serum collected from vaccinated subjects, but the structure of the antibodies involved (present in the serum) is/are not disclosed.
In view of this uncertainty and the lack of a representative number of examples of the claimed genus, the claims are rejected for lack of adequate written description support.
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.
Claim 20, 21 and 25-42 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 20 recites, “An assay for SARS-CoV-2 replication comprising:
contacting a cultured cell expressing or containing a recombinant SARS-CoV-2 nucleic acid segment encoding a heterologous S protein and a reporter protein replacing an ORF7a encoding segment forming a test cell;
contacting the test cell with a test agent; and
assessing the replication of the recombinant SARS-CoV-2 nucleic acid segment in the presence of the test agent.”
However, the preamble of the claim recites, “for SARS-CoV-2 replication”, while the assessing step is focused on the replication of the recombinant SARS-CoV-2 nucleic acid segment, which is not a genome of such a virus, but rather a sequence that encodes the S protein and a reporter protein. Therefore, it is unclear which replication is to be assayed by this assay.
Claim 20 is also indefinite because the claimed assay is for SARS-CoV-2 replication and this assay involves the use of a test cell and a test agent and assessing the replication of the recombinant SARS-CoV-2 nucleic acid segment. However, the claimed assay does not indicate what the test agent is being tested for. For example, the claimed assay states that it is for SARS-CoV-2 replication and that the replication of the recombinant SARS-CoV-2 nucleic acid segment is assessed in the presence of the test agent, but it is unclear if the replication is assessed for increased replication, steady replication or decreased replication.
Claim 20 is also indefinite because it recites, “contacting a cultured cell expressing or containing a recombinant SARS-CoV-2 nucleic acid segment encoding a heterologous S protein…”. However, it is unclear what the S protein is heterologous to since the only mention of a SARS-CoV-2 sequence in the claim is the identified portion in quotations. Is the S protein heterologous to the cultured cell, to SARS-CoV-2, or is the S protein from another coronavirus?
Claim 20 is also indefinite because it recites, “contacting a cultured cell expressing or containing a recombinant SARS-CoV-2 nucleic acid segment encoding a heterologous S protein and a reporter protein replacing an ORF7a encoding segment…”. Is the recombinant SARS-CoV-2 a nucleic acid segment only encoding the S protein and a reporter protein or is the nucleic acid segment a SARS-CoV-2 genome with an ORF7a encoding segment being replaced by a reporter protein. The latter would be appropriate since the claim begins with “An assay for SARS-CoV-2 replication…”.
Since claim 20 is rejected, claims 21 and 25-42 are also rejected since they depend from claim 20, but do not remedy these deficiencies.
Claim 26 recites, “…wherein the nucleic acid encoding the heterologous S protein has a nucleic acid sequence of SEQ ID NO: 2.”
Claim 28 recites, “…wherein the encoded heterologous S protein has an amino acid sequence of SEQ ID NO: 3.”
Claim 31 recites, “…wherein the recombinant SARS-CoV-2 nucleic acid segment has a nucleic acid sequence of SEQ ID NO: 1.”
The limitation of “has a nucleic acid sequence of” and “has an amino acid sequence of” is interpreted as a fragments of the claimed sequence or a full-length sequence comprising the claimed SEQ ID NO:. As a result, it is unclear whether the claims are drawn to fragments or full-length sequences.
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.
Claim(s) 20, 21, 26, 28-40 and 42 are rejected under 35 U.S.C. 102a1 as being anticipated by Chiem et al. (Journal of Virology, 2021, Vol. 95, Issue 7, pages 1-15 [Epub 1/11/2021]) as evidenced by Genbank MN985325 and GenBank Accession QHO60594 (both published 11/8/21) and Piepenbrink et al. (Cell Reports Medicine, 2, 100218, epub 2/25/2021).
The claimed invention is drawn to an assay for SARS-CoV-2 replication comprising:
contacting a cultured cell expressing or containing a recombinant SARS-CoV-2 nucleic acid segment encoding a heterologous S protein and a reporter protein replacing an ORF7a encoding segment forming a test cell;
contacting the test cell with a test agent; and
assessing the replication of the recombinant SARS-CoV-2 nucleic acid segment in the presence of the test agent. [claim 20]
As established in the 35 USC 112b rejection over claim 20 above, the limitation of “heterologous S protein” is indefinite and will be interpreted as any SARS-CoV-2 S protein.
The cultured cell is a Vero cell [claim 21]; the reporter protein is a fluorescent (mNeonGreen) or luminescent (nanoluciferase) protein [claims 32-34]; the cultured cell is assayed in a 96 well plate (which is a multiwell plate) [claims 36-37]; the cultured cell is incubated for about 24 hours before measuring a signal produced by the reporter protein [claim 38]; the test agent is an antibody obtained from a subject previously infected with a non-Omicron SARS-CoV-2 [claims 39-40]; and assessing the replication comprises measuring a reporter signal [claim 42].
The nucleic acid encoding the heterologous S protein has a nucleic acid sequence of SEQ ID NO: 2 [claim 26]; the encoded heterologous S protein has an amino acid sequence of SEQ ID NO: 3 [claim 28]; and the recombinant SARS-CoV-2 nucleic acid segment is at least 95%, at least 99% identical to SEQ ID NO: 1 or has a nucleic acid sequence of SEQ ID NO: 1 [claims 29-31]. As established above in the 35 USC 112b rejection over claims 26, 28 and 31, these claims include fragments of the claimed SEQ ID NO:s and therefore, if the prior art teaches a sequence that comprises a fragment of the claimed SEQ ID NO:, then these claims are anticipated.
The Prior Art
Chiem et al. teach the generation of a recombinant SARS-CoV-2 genome and a recombinant SARS-CoV-2 virus that expresses Venus, mCherry or Nluc reporter proteins in place of the OR7a gene. [see Materials and Methods and Figure 1a] Chiem et al. also teach that mNeonGreen and green fluorescent protein (GFP) are also suitable reporter proteins. [see last paragraph of page 2] Venus, mCherry, mNeonGreen and GFP are examples of fluorescent reporter proteins and Nluc (which is also known as nanoluciferase) is a luminescent protein. The genome of the SARS-CoV-2 used that of GenBank Accession MN985325. [see Materials and Methods]
As evidenced by GenBank Accession MN985325, the genome of SARS-CoV-2 USA/WA1/2020 is 99% identical to SEQ ID NO: 1 of the instant invention and at nucleotides 21563…25384 [which represents the coding region of the spike protein]. In addition, MN985325 is 96.9% identical to SEQ ID NO: 2 of the instant invention. GenBank Accession QHO60594 represents the Spike protein expressed by the genome of MN985325. This spike protein is 96.4% identical to SEQ ID NO: 3 of the instant invention. Therefore, these sequences either meet the claim limitations of percent identity or meet the claim limitations pertaining to fragments of the claimed SEQ ID NO:s.
Chiem et al. teach the use of the recombinant SARS-CoV-2 (rSARS) in testing for antiviral compounds that may interfere with virus replication. Specifically, Chiem et al. use Vero E6 cells plated and cultured in a 96 well plate as a target for the rSARS and antiviral compounds. [see page 7] The rSARS was absorbed onto the cultured cells for 1 hour followed by adding postinfection medium containing serial dilutions of remdesivir or 1212C2. [see figures 4 and 5] The 1212C2 antibody is a fully human monoclonal antibody was derived from an IgM memory B cell of a COVID-19 patient, which was a non-Omicron SARS-CoV-2, as evidenced by Piepenbrink et al. [see page 13] After 24 hours of incubating the VeroE6 cells with rSARS and remdesivir or 1212C2, the cells are fixed and any expressed Venus, mCherry or Nluc are visualized, which was indicative of rSARS replication (replication of a Spike protein nucleic acid segment). [see page 13 and Figures 4 and 5]
Therefore, Chiem et al. anticipate the instant invention.
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.
Claim(s) 25, 27, 28, 35 and 41 are rejected under 35 U.S.C. 103 as being unpatentable over Chiem et al. as evidenced by Genbank MN985325 and QHO60594 and Piepenbrink et al. as applied to claims 20, 21, 26, 28-40 and 42 above, and further in view of Baum et al. (US PGPub 20230125469).
The claimed invention also requires that the nucleic acid segment encoding the heterologous S protein has a nucleic acid sequence that is at least 98% identical to SEQ ID NO: 2 [claim 25]; the encoded heterologous S protein has an amino acid sequence that is at least 98% identical to SEQ ID NO: 3 [claim 27] or the heterologous S protein comprises the full-length of SEQ ID NO: 3 [alternative interpretation of claim 28]; the heterologous S protein is an Omicron variant S protein [claim 35]; and the antibody (test agent) is obtained from a vaccinated subject [claim 41].
The teachings of Chiem et al. are summarized above, however, they do not teach a nucleic acid sequence with at least 98% identity to SEQ ID NO: 2, an amino acid sequence with at least 98% identity to SEQ ID NO: 3, that the heterologous S protein is from an Omicron variant and the antibody is obtained from a vaccinated subject.
Baum et al. teach SARS-CoV-2 spike proteins comprising the amino acid sequence of SEQ ID NO: 1072, which is identical to SEQ ID NO: 3 of the instant invention and is from an Omicron variant B.1.1.529 of SARS-CoV-2. [see paragraph 94] Baum et al. also teach the generation of antibodies by vaccinating transgenic mice with vector expressing the Spike protein of SEQ ID NO: 1008, which is encoded by GenBank Accession MN908947.3. [see paragraph 263] MN908947.3, (a copy of which is provided with this Office action) encodes this spike protein as nucleotides 21563 to 25384 and is 98.6% identical to SEQ ID NO: 2 of the instant invention. Baum et al. also teach the generation of human antibodies specific for SARS-CoV-2 by administering a CoV-S polypeptide vaccine to transgenic mice and isolating antibodies therefrom. [see paragraphs 156-160]
It would have been obvious to one of ordinary skill in the art to modify the assays and compositions taught by Chiem et al. in order to employ a rSARS that comprises a nucleic acid sequence with at least 98% identity to SEQ ID NO: 2, which also encodes an amino acid sequence with at least 98% identity to SEQ ID NO: 3, that the heterologous S protein is from an Omicron variant and the antibody (test agent) is obtained from a vaccinated subject. One would have been motivated to do so, given the suggestion by Chiem et al. that their recombinant SARS-CoV-2 virus can be used to test the antiviral properties of a human monoclonal antibody, which was obtained from a patient infected with SARS-CoV-2. There would have been a reasonable expectation of success, given the knowledge that additional SARS-CoV-2 spike protein and nucleic acid sequence encoding additional SARS-CoV-2 spike proteins, which is of an Omicron variant were previously known and that human monoclonal antibodies can be obtained from vaccinated subjects, as taught by Baum et al. 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.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BENJAMIN P BLUMEL whose telephone number is (571)272-4960. The examiner can normally be reached M-F 8-5 EST.
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/BENJAMIN P BLUMEL/Primary Examiner, Art Unit 1671
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