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 .
Status of the Claims
Claims 5-10 are cancelled by Applicant. Claims 1-4, 11-16, and 18-25 are pending and examined here.
Priority
This application, filed 03/29/2022, claims benefit to PRO 63/167,773, filed 03/30/2021. This benefit is acknowledged and the claims examined herein are treated as having an effective filing date of 03/30/2021.
Information Disclosure Statement
The Information Disclosure Statement filed 03/16/2026 is acknowledged and has been considered.
Amended Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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 1-4, 11-16, 18-21, and 23-24 are rejected under 35 U.S.C. 103 as being unpatentable over US2024/0277831 A1, “POLYPEPTIDES, COMPOSITIONS, AND THEIR USE TO TREAT OR LIMIT DEVELOPMENT OF AN INFECTION” (priority date 08/11/2020, referred to herein as King) in view of US 2021/0246170, “COMPOSITIONS AND METHODS FOR PREVENTING AND TREATING CORONAVIRUS INFECTION – SARS-COV-2 VACCINES” (priority date 09/21/2020, referred to herein as Janssen) as evidenced by US 2022/0096624 A1 (filed 09/29/2020, referred to herein as Trentin).
King’s general disclosure relates to the use of spike protein polypeptides. In particular, King teaches the use of a spike protein polypeptide, “SARS-COV-2 S-2P Trimer” (King, SEQ. ID. 161, referred to as S-2P). Below is the sequence alignment of the S-2P amino acid sequence taught by King (top row) compared to elected SEQ. ID: 10 (bottom row) of this application:
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Regarding claims 1, 10, 16, 20 and 21, King teaches a method for detecting anti-SARS-CoV-2 antibody in a sample by ELISA assay (para. 0269, line 1) comprising contacting the sample with the S-2P polypeptide (para. 0269, lines 1-9) and detecting the presence of an anti-SARS-CoV-2 antibody bound to the peptide using HRP-conjugated secondary antibodies (para. 0269, lines 9-12). King teaches that the D614G mutation could be introduced into their polypeptides in order to study naturally occurring variant mutations (para. 0056, lines 1-10). King teaches that the S-2P polypeptide comprises the K986P and V987P mutations (King SEQ. ID NO: 161 as shown above). Regarding claim 4, King teaches that the S-2P contains a 682-SGAG-685 substitution at the furin cleavage site (SEQ. ID NO: 161 as shown above, para. 0243, lines 14-16). King teaches that the S-2P polypeptide comprises the spike protein sequence of SEQ ID NO: 3 (King SEQ. ID NO: 161 as shown above) and is further linked to the first 10 amino acids, i.e. ELGKYEQYIK, of SEQ ID NO: 24. King teaches that various components of the polypeptides used in their methods may, but are not required to, contain sequences useful for promoting expression or purification of the polypeptide (para. 0081, lines 1-12). This is considered to teach that components of the spike polypeptides that are included for the purposes of purification, rather than for spike protein function, are optional.
However, King differs from the claimed invention in that it contains a mu-phosphatase signal peptide as an N-terminal signal peptide sequence, a C-terminal TEV cleavage site, is 1281 amino acids long, and does not teach a specific polypeptide comprising the D614G or R682A.
Regarding the D614G mutation, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the S-2P polypeptide used by King by including the D614G mutation. Doing so would allow for the investigation of a mutation that occurs in naturally occurring variants, as taught by King (para. 0056, lines 1-10) with a reasonable expectation of success as a preferred embodiment of the S-2P polypeptide taught by King.
Regarding the mu-phosphatase signal peptide, it would have been obvious to one of skill in the art before the effective filing date of the claimed invention to modify the S-2P polypeptide used by King by removing the mu-phosphatase signal peptide and TEV cleavage site, which are included in order to facilitate purification of the polypeptide. A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments. Merck & Co. v. Biocraft Labs., Inc. 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989). See also Upsher-Smith Labs. v. Pamlab, LLC, 412 F.3d 1319, 1323, 75 USPQ2d 1213, 1215 (Fed. Cir. 2005) (reference disclosing optional inclusion of a particular component teaches compositions that both do and do not contain that component). In this case, although the mu-phosphatase signal peptide and TEV cleavage site are included in a preferred embodiment of the polypeptide taught by King, it is taught to be optional and removing it is considered to be obvious. This is further evidenced by US 2022/0096624 A1 (filed 09/29/2020) which teaches that, when producing spike protein variants with a trimerization domain, the inclusion of a protease cleavage site like TEV is optional (paras. 0156-0160). The removal of the mu-phosphatase signal peptide and TEV cleavage site from the S-2P polypeptide results in a 1236 amino acid polypeptide.
However, the modified S-2P polypeptide taught by King differs from the claimed invention in that does not teach a specific polypeptide comprising the R682A mutation.
Janssen teaches that the R682A (para. 1332, lines 11-15) or the R682S (para. 0260, lines 1-6) mutation can be used to make a SARS-CoV-2 spike protein polypeptide with furin cleavage resistance.
It would have been obvious to one of ordinary skill before the effective filing date to modify the S-2P polypeptide taught by King by substituting the R682S mutation for the R682A mutation as taught by Janssen. Doing so is considered to be a choice of preference by an artisan since both mutations are known in the art to enable furin cleavage resistance to a SARS-CoV-2 spike protein polypeptide. An artisan would have a reasonable expectation of success making this modification since introducing mutations is a well-known practice in the art of protein analysis and both mutations are well-known to be used for enabling furin cleavage resistance to SARS-CoV-2 spike protein polypeptides.
Regarding claim 2, King teaches that antibody titers are measured with the ELISA assay (para. 0267, lines 18-19).
Regarding claim 3, King teaches that the measuring mouse and human sera samples with the ELISA assay using the S-2P polypeptide (para. 0269, lines 6-9).
However, King does not teach diagnosing an animal as having a SARS-CoV-2 infection when antibodies are detected or a polypeptide with the R682A mutation.
Regarding claim 3, Janssen teaches a method of diagnosing a subject with a coronavirus infection comprising measuring the level of an anti-coronavirus antibody in a sample (para. 0479, lines 1-6).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use the ELISA assay with the S-2P polypeptide taught by King in order diagnose a subject as having a SARS-CoV-2 infection as taught by Janssen. An artisan would have been motivated to do so in order to effectively determine whether a subject would potentially benefit from treatment, such as the treatment methods taught by King (para. 0011, lines 1-7). An artisan would have a reasonable expectation of success because, as taught by Janssen, determining the antibody titer, like in the ELISA method taught by King, in a subject sample is sufficient to diagnose the subject with an infection (para. 0479, lines 1-6).
Regarding claim 4, King teaches that the S-2P contains a 682-SGAG-685 substitution at the furin cleavage site (SEQ. ID NO: 161 as shown above, para. 0243, lines 14-16).
Regarding claims 11, 12, and 13, King teaches the S-2P polypeptide comprises the foldon trimer motif of SEQ ID NO: 16 (King SEQ. ID NO: 161 as shown above).
Regarding claim 14, King teaches the S-2P polypeptide is biotinylated and conjugated to streptavidin-APC detectable marker (para. 0274, lines 1-5).
Regarding claim 15, including the modifications described above regarding individual mutations and the removal of purification-oriented regions, King teaches a polypeptide with over 99% sequence identity to SEQ ID NO.: 10.
Regarding claim 18, King teaches that the S-2P polypeptide is a trimer (para. 0274, line 1).
Regarding claim 19, King teaches that the S-2P polypeptide is immobilized on a 384-well plate (para. 0269, lines 1-3).
Regarding claims 23 and 24, King teaches a method of making the polypeptide comprising transfecting a cell with a vector expressing the polypeptide and culturing the cell under conditions for expression (para. 0244, lines 1-10).
New Claim Rejections - 35 USC § 103
Claims 22 and 25 are rejected under 35 U.S.C. 103 as being unpatentable over King in view of Janssen as applied to claims 1 and 20 above, and further in view of US 2024/0277831 (filed 09/29/2020, referred to herein as Trentin).
The teachings of King in view of Janssen, as applied to claims 20-21 and 23-24 above, are incorporated herein.
However, the modified S-2P polypeptide taught by King in view of Janssen differs from the claimed polypeptide of claim 22 by using a 8xHis tag instead of a 6xHis tag.
Trentin teaches that, when tagging a SAR-CoV-2 spike protein for purification, a variety of purification tags can be used including His tags of various lengths, including 6xHis.
It would have been obvious to one of skill in the art before the effective filing date of the claimed invention to modify the polypeptide taught and made by King in view of Janssen by substituting the 8xHis tag for a 6xHis tag. Doing so is considered a Simple substitution of one known element for another to obtain predictable results (See MPEP 2143(I)(B)). The use of His tags of various lengths, including 8xHis and 6xHis, are well known in the art to be usable as tags for the predictable purification of tagged polypeptides.
Response to Arguments
Applicant's arguments filed 03/16/2026 have been fully considered but they are not persuasive for the following reasons:
Regarding the remarks on pages 1 and 2 on the rejection of claims 1, 2, 4-9, 11-15, 18, and 19 over King, Applicant argues that King does not teach the new limitations of claim 1 as amended.
This argument is not persuasive. The rejection of claim 1 has been amended above in response to Applicant’s amendments. Briefly, King teaches that the segments of the S-2P polypeptide directed toward purification, such as the signal peptide sequence and the TEV cleavage site are not required.
Further regarding the remarks on pages 2-5, Applicant argues that the polypeptide, as claimed, is non-obvious because of its large production yield.
This argument is not persuasive. In response to applicant's argument that the claimed polypeptide has a large production yield, the fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985). In this case, modifications to the S-2P polypeptide taught by King are considered obvious regardless of whether a further advantage, such as a large producaiton yield, has been contemplated in the prior art.
Conclusion
No claims are allowable.
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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/C.E./Examiner, Art Unit 1677
/BAO-THUY L NGUYEN/Supervisory Patent Examiner, Art Unit 1677 September 28, 2026
