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, 25-28 and 30-42 are examined on the merits.
Specification
(New Objection Necessitated by Amendment) The specification is objected to as failing to provide proper antecedent basis for the claimed subject matter. See 37 CFR 1.75(d)(1) and MPEP § 608.01(o). Correction of the following is required: “BA.1 sub-variant” found in amended claim 35.
Drawings
(Withdrawn in view of amendments) The drawings are objected to because the text of figures 2 and 7A are unclear.
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.
(Prior Rejection Maintained and expanded to new limitations presented by Amendment) 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.
Claim 20 requires: an assay for SARS-CoV-2 replication comprising:
contacting a cultured cell expressing or containing a recombinant SARS-CoV-2 nucleic acid segment comprising a sequence at least 95% identical to SEQ ID NO: 1 encoding a heterologous Omicron variant S protein comprising an amino acid sequence at least 95% identical to SEQ ID NO: 3 and a reporter protein replacing an ORF7a encoding segment forming a test cell;
contacting the test cell with a test agent; and
assessing inhibition of replication of the recombinant SARS-CoV-2 nucleic acid segment in the presence of the test agent by measuring a reporter signal produce by the reporter protein.”
In claims 39-41, which depend from claim 20, applicants have amended the claims to replace “antibody” with “serum obtained from a subject”. However, serum contains a mixture antibodies among other blood products.
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 (serum obtained from a subject) 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, since serum employed by applicant is a mixture of monoclonal antibodies, the serum claimed includes antibodies.
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 addition and in response to applicant’s amendment to include serum as the test agent, Bosnjak et al. (Cellular and Molecular Immunology, 2021, Vol. 18, Pages 936-944) teach that collecting serum from patients previously infected with COVID-19 does not guarantee the collection of potent, neutralizing antibodies since collection of the sera at different stages of the infection and the severity of the illness have an impact on the “quality” of the sera. [see left column of page 943]
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.
Response to arguments:
Applicant’s response has been considered in full, but it is not persuasive:
As discussed above, serum contains a mixture of antibodies. Therefore, the issues identified above related to structure-function correlation, representative number of species, the guidance based on Amgen V. Sanofi and the teachings of Bosnjak et al., applicants are not in possession of the claimed test agent being serum and what this serum contains, such as antibodies.
(New Rejection Necessitated by Amendments) Claim 35 is 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. This is a new matter rejection
The terms “BA.1 sub-variant” as recited in claim 35 is not supported by the original disclosure or claim as filed.
Applicant’s amendment, filed 7/13/26, directs to support to pages 2-6, 16-17 and 24, and asserts that no new matter has been added.
However, the specification as filed does not provide sufficient written description of the above-mentioned limitations. The specification does not provide sufficient support for the recitation “BA.1 sub-variant”. The specification specifically disclose BA.1 in paragraph 57, whereas the amended claims now recites the limitation of BA.1 sub-variant, which is not described in the specification. Therefore, the claims represent a departure from the specification and claims as originally filed.
Such limitations recited in the present claims, which did not appear in the specification, as filed, introduce new concepts and violate the description requirement of the first paragraph of 35 U.S.C. §112.
Applicant is required to cancel the new matter in the response to this Office Action. Alternatively, applicant is invited to provide sufficient written support for the “limitations” indicated above. See MPEP §714.02, §2163.05-06 and §2173.05(i).
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, 25-28 and 30-42 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.
(Withdrawn Rejection in view of Amendments) 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 comprising a sequence at least 95% identical to SEQ ID NO: 1 encoding a heterologous Omicron variant S protein comprising an amino acid sequence at least 95% identical to SEQ ID NO: 3 and a reporter protein replacing an ORF7a encoding segment forming a test cell;
contacting the test cell with a test agent; and
assessing inhibition of replication of the recombinant SARS-CoV-2 nucleic acid segment in the presence of the test agent by measuring a reporter signal produce by the reporter protein.”
(Withdrawn Rejection in view of Amendments) 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.
(Prior Rejection Maintained) Claim 20 is also indefinite because it recites, “contacting a cultured cell expressing or containing a recombinant SARS-CoV-2 nucleic acid segment comprising a sequence at least 95% identical to SEQ ID NO: 1 encoding a heterologous Omicron variant 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?
Response to arguments:
Applicant’s arguments have been considered in full, but are not persuasive:
The genome of SARS-CoV-2 Omicron B.1.1.529 (GenBank Accession OL869974, 12/15/2021) is 99% identical to SEQ ID NO: 1 of the instant invention:
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Therefore, the recitation of “a heterologous Omicron Variant S protein” is unclear based on the scope of the claimed nucleic acid and amino acid sequences.
The rejection can be overcome is “heterologous” is removed from the claim.
(Withdrawn Rejection in view of Amendments) Claim 20 is also indefinite because it recites, “contacting a cultured cell expressing or containing a recombinant SARS-CoV-2 nucleic acid segment comprising a sequence at least 95% identical to SEQ ID NO: 1 encoding a heterologous Omicron variant S protein comprising an amino acid sequence at least 95% identical to SEQ ID NO: 3 and a reporter protein replacing an ORF7a encoding segment forming a test cell…”. 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…”.
(Prior Rejection Maintained) Claim 26 recites, “…wherein the nucleic acid encoding the heterologous S protein has a nucleic acid sequence of SEQ ID NO: 2.”
(Prior Rejection Maintained) Claim 28 recites, “…wherein the encoded heterologous S protein has an amino acid sequence of SEQ ID NO: 3.”
(Prior Rejection Maintained) 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.
Response to arguments:
Applicant’s arguments have been considered in full, but are not persuasive:
As written, the claims are drawn to fragments of the recited SEQ ID NO:s. This rejection can be overcome by amending claims 26, 28 and 31 to recite “has the” in place of either “has a” or “has an”.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
(New Rejection Necessitated by Amendments) Claims 26, 28 and 31 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claims 26, 28 and 31 recite, “has a nucleic acid sequence of” and “has an amino acid sequence of”. However, claim 20 has been amended to recite “at least 95% identical to SEQ ID NO:”. Since the examiner is interpreting “has a” and “has an” as including fragments of claimed sequences and claim 20 recites a high degree of sequence identity, the fragments of claims 26, 28 and 31 broaden the scope of claim 20. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
This rejection can be overcome by amending claims 26, 28 and 31 to recite “has the” in place of either “has a” or “has an”.
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.
(Prior Rejection Maintained) Claim(s) 20, 21, 26, 28, 30-40 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 comprising a sequence at least 95% identical to SEQ ID NO: 1 encoding a heterologous Omicron variant S protein comprising an amino acid sequence at least 95% identical to SEQ ID NO: 3 and a reporter protein replacing an ORF7a encoding segment forming a test cell;
contacting the test cell with a test agent; and
assessing inhibition of replication of the recombinant SARS-CoV-2 nucleic acid segment in the presence of the test agent by measuring a reporter signal produce by the reporter protein. [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 serum 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 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.
Response to arguments:
Applicant presents the following arguments in traversal of the rejection:
Applicants argue that the SARS-CoV-2 spike protein and nucleic acid sequence encoding it as taught by Chiem et al. is not a Omicron variant S protein and applicants state in the response dated 7/13/26: “The specification expressly describes the claimed construct: the complete Omicron (BA.1) spike gene is engineered into the WA1/2020 backbone with the ORF7a reporter (I [0030], FIG. 2, Example 1). Because Chiem et al. lacks this specific structural limitation, the heterologous Omicron variant S protein required by every recited claim, the reference does not anticipate the claims.” and “Sharing a degree of overall sequence identity with the Omicron spike does not make WA1/2020's spike an Omicron variant spike, just as a 96% identity between human and chimpanzee proteins does not make them the same protein for purposes of patent claiming.”
In response, the specification does not define the Omicron variant S protein to have a specific singular structure (i.e., amino acid sequence) or a specific set of amino acid residues present in said protein that specifically defines what the Omicron variant S protein must possess. Furthermore, paragraph 5 of the instant specification states that the encoded S protein can include any combination of amino acid substitutions, insertions or deletions [see last 5 lines of page 4 of specification]. Paragraph 49 mentions amino acid residues at specific positions of an engineered Omicron spike, but this discussion is not a definition of what constitutes an Omicron variant S protein as presently claimed. Therefore, the claims rejected herein permits SARS-CoV-2 spike proteins having at least 95% or 98% sequence identity to SEQ ID NO: 3, and a nucleic acid sequence encoding the Omicron variant S protein with at least 95% or 98% identity to SEQ ID NO:s 1 and 2, or fragments thereof. As stated in the previous Office action, 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 and therefore meet the structural requirements of the claimed SARS-CoV-2 sequences. Furthermore, the genome of SARS-CoV-2 Omicron B.1.1.529 (GenBank Accession OL869974, 12/15/2021) is 99% identical to SEQ ID NO: 1 of the instant invention (see Appendix A), which would possess an Omicron S protein within the claimed scope without it being heterologous.
Therefore, Chiem et al. anticipates 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.
(Prior Rejection Maintained and extended to new limitations present in amendments) 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, 30-40 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]; that the heterologous S protein is an Omicron BA.1 sub-variant S protein [claim 35]; and the serum (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, and the serum 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, which is a BA.1 sub-variant. [see paragraph 94] Baum et al. also teach the generation of antibodies (which are isolated from serum) 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 BA.1 sub-variant and the serum (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.
Response to arguments:
Applicant presents the following arguments in traversal of the rejection:
The Examiner wishes to inform applicants of the following guidelines pertaining to arguments that mirror supported claims or facts but are not founded on a factual basis.
In the MPEP:
MPEP §2145 Consideration of Applicant's Rebuttal Arguments:
(I) ARGUMENT DOES NOT REPLACE EVIDENCE WHERE EVIDENCE IS NECESSARY
Attorney argument is not evidence unless it is an admission, in which case, an examiner may use the admission in making a rejection. See MPEP § 2129 and§ 2144.03 for a discussion of admissions as prior art.
The arguments of counsel cannot take the place of evidence in the record. In re Schulze, 346 F.2d 600, 602,145 USPQ 716, 718 (CCPA 1965); In re Geisler, 116F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997) (“An assertion of what seems to follow from common experience is just attorney argument and not the kind of factual evidence that is required to rebut a prima facie case of obviousness.”). See MPEP § 716.01(c) for examples of attorney statements which are not evidence and which must be supported by an appropriate affidavit or declaration.
MPEP §716.01 (c) Probative Value of Objective Evidence
I. TO BE OF PROBATIVE VALUE, ANY OBJECTIVE EVIDENCE SHOULD BE SUPPORTED BY ACTUAL PROOF
Objective evidence which must be factually supported by an appropriate affidavit or declaration to be of probative value includes evidence of unexpected results, commercial success, solution of a long-felt need, inoperability of the prior art, invention before the date of the reference, and allegations that the author(s) of the prior art derived the disclosed subject matter from the applicant. See, for example, In re De Blauwe, 736 F.2d 699, 705, 222 USPQ191, 196 (Fed. Cir. 1984) (“It is well settled that unexpected results must be established by factual evidence.” “[A]ppellants have not presented any experimental data showing that prior heat-shrinkable articles split. Due to the absence of tests comparing appellant’s heat shrinkable articles with those of the closest prior art, we conclude that appellant’s assertions of unexpected results constitute mere argument.”). See also In re Lindner, 457 F.2d 506, 508, 173 USPQ 356,358 (CCPA 1972); Ex parte George, 21 USPQ2d 1058(Bd. Pat. App. & Inter. 1991).
II. ATTORNEY ARGUMENTS CANNOT TAKE THE PLACE OF EVIDENCE
The arguments of counsel cannot take the place of evidence in the record. In re Schulze, 346 F.2d 600, 602,145 USPQ 716, 718 (CCPA 1965). Examples of attorney statements which are not evidence and which must be supported by an appropriate affidavit or declaration include statements regarding unexpected results, commercial success, solution of a long-felt need, inoperability of the prior art, invention before the date of the reference, and allegations that the author(s) of the prior art derived the disclosed subject matter from the applicant.
See MPEP § 2145 generally for case law pertinent to the consideration of applicant’s rebuttal arguments.
III. OPINION EVIDENCE
Although factual evidence is preferable to opinion testimony, such testimony is entitled to consideration and some weight so long as the opinion is not on the ultimate legal conclusion at issue. While an opinion as to a legal conclusion is not entitled to any weight, the underlying basis for the opinion may be persuasive. In re Chilowsky,306 F.2d 908, 134 USPQ 515 (CCPA 1962) (expert opinion that an application meets the requirements of 35U.S.C. 112 is not entitled to any weight; however, facts supporting a basis for deciding that the specification complies with 35 U.S.C. 112 are entitled to some weight); In re Lindell, 385 F.2d 453, 155 USPQ 521 (CCPA 1967)(Although an affiant’s or declarant’s opinion on the ultimate legal issue is not evidence in the case, “some weight ought to be given to a persuasively supported statement of one skilled in the art on what was not obvious to him.” 385 F.2d at 456, 155 USPQ at 524 (emphasis in original)).
Presently and in view of the guidance from MPEP §2145 and §716 above, applicants
statements of:
“The Omicron BA.1 spike protein carries more than 30 amino acid substitutions relative to the WA1/2020 spike, including changes in the S1/S2 furin cleavage site and transmembrane domain that are known to affect viral assembly, cell fusion, and replication kinetics. A skilled artisan in early 2022 would have had substantial reason to doubt that substituting the full Omicron spike into a WA1/2020 backbone, while maintaining replication competence necessary for this assay, would succeed. Pseudovirus systems which use non-replicating vectors are fundamentally different from the replication-competent chimeric virus claimed here. The skilled artisan would have recognized that replication competence imposes stringent compatibility requirements between the spike protein and the remaining viral machinery that are absent in pseudovirus systems.”
Is interpreted as opinion of counsel since these arguments are not supported by evidence. Furthermore, Chiem et al. teach that inserting heterologous sequences into the genome of a SARS-CoV-2 does not impact virus infection and expression of said heterologous sequence in view of Figure 2 of Chiem et al.
In addition, Chiem et al. and Baum et al. do not render obvious the engineering a full-length heterologous Omicron spike into a replication-competent SARS-CoV-2 backbone for use in a neutralization assay. In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., claimed invention does not specifically require that a Omicron spike protein encoding sequence be placed into a replication-competent SARS-CoV-2 backbone) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). In addition, applicants argue that Chiem and Baum do not suggest using the claimed WA1/2020 backbone that expresses the full Omicron spike protein to assess cross-reactive serum neutralization from prior non-Omicron Infected or vaccinated individuals. However, the claimed assay does not require testing for serum cross-reactivity or that the assay specifically uses a WA1/2020 backbone that expresses the full Omicron spike protein. Presently, the claimed assay requires the use of a recombinant SARS-CoV-2 nucleic acid sequence with at least 95% identity to SEQ ID NO: 1 and it encodes an amino acid sequence with at least 95% identity to SEQ ID NO: 3, which is a heterologous Omicron variant S protein. The nucleic acid also comprises SEQ ID NO:2, or a sequence that is at least 98% identical to it.
Therefore, the teachings of Chiem et al. as evidenced by Genbank MN985325 and QHO60594 and Piepenbrink et al., and further in view of Baum et al. (US PGPub 20230125469) render obvious the instant invention.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/BENJAMIN P BLUMEL/Primary Examiner, Art Unit 1671
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