DETAILED ACTION
Disposition of Claims
Claims 12-23 were pending. Claims 1-11, 13, and 23 have been cancelled. Amendments to claims 12, 14-15, and 21-22 are acknowledged and entered. Claims 12 and 14-22 will be examined on their merits.
Examiner’s Note
All paragraph numbers (¶) throughout this office action, unless otherwise noted, are from the US PGPub of this application US20230220012A1, Published 07/13/2023. Amendments to the specification presented on 12/19/2025 are acknowledged and entered.
Response to Arguments
Applicant's arguments filed 12/19/2025 regarding the previous Office action dated 08/21/2025 have been fully considered. If they have been found to be persuasive, the objection/rejection has been withdrawn below. Likewise, if a rejection/objection has not been recited, said rejection/objection has been withdrawn. If the arguments have not been found to be persuasive, or if there are arguments presented over art that has been utilized in withdrawn rejections but utilized in new rejections, the arguments will be addressed fully with the objection/rejection below.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-(d) prior to declaration of an interference, a certified English translation of the foreign application would need be submitted. 37 CFR 41.154(b) and 41.202(e).
Failure to provide a certified translation may result in no benefit being accorded for the non-English application if intervening art is utilized in a rejection.
Specification
(Objection withdrawn.) The objection to the disclosure is withdrawn in light of the amendments to the specification.
Drawings and Specification; Sequence Disclosure Requirements
(Objection withdrawn.) The objection to the drawings and specification is withdrawn in light of the amendments to the specification and the updated sequence deposit.
Claim Objections
(Objection withdrawn.) The objection to Claim 12 is withdrawn in light of the amendments to the claim.
(New Objection.) Claims 12, 21, and 22 are objected to because of the following informalities: it is suggested with how claims 12, 21, and 22 are amended, to instead utilize “a polypeptide” in line 2 (claim 12), line 6 (claim 21), and line 4 (claim 22) as it is followed by a postpositive modifying participial phrase that provides descriptive details as to the specific noun (“a polypeptide”) and makes it clear that said polypeptide can only be selected from those listed in the following Markush group. The Office understands the Applicant made this change of the article (indefinite article “a” to definite article “the”) because of how claim 12 was previously interpreted; the issue was the claim was previously drawn to “a polypeptide of SEQ ID NOs: 1 to 22” (which only used a prepositional phrase “of SEQ ID NOs: 1-22” to modify “a polypeptide”), but now with the amendments and the use of the postpositive modifying participial phrase “selected from the group consisting of” the more grammatically correct way of presenting this claim would be to have “a polypeptide selected from the group consisting of SEQ ID NOs: 1-22”. The interpretation in this suggestion is that the polypeptide must be one of those listed in the Markush group (SEQ ID NOs: 1-22) and not “fragments thereof”; there is no ambiguity in that the sequence must comprise the entire sequence of one of those sequences listed in the Markush group. The previous draft of the claim which used “a polypeptide of SEQ ID NOs: 1-22” allowed for the interpretation of “fragments/derivatives thereof” while the use of “selected from the group consisting of” does not allow for the selection of fragments unless specifically drafted that way in the claim.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b); Second Paragraph
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
(Rejection withdrawn.) The rejection of Claim 15 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn in light of the amendments to the claim.
(Rejection withdrawn.) The rejection of Claim 21 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn in light of the amendments to the claim.
(Rejection withdrawn.) The rejection of Claim 23 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn in light of the cancellation of said claim.
Claim Interpretation
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art.
Claim 12 is drawn to a recombinant antigen comprising a cell membrane permeation domain comprising a polypeptide selected from the group consisting of any one of SEQ ID NOs: 1 to 22 derived from human leucine-rich repeat-containing protein 24 (LRRC241 and a severe acute respiratory syndrome coronavirus type 2 {SARS-CoV-2) receptor binding domain (RBD).
Further limitations on the recombinant antigen according to claim 12 are wherein the SARS- CoV-2 RBD comprises SEQ ID NO: 24 (claim 14); and wherein the recombinant antigen comprises at least one sequence selected from the group consisting of SEQ ID NOs: 26 to 47 (claim 15).
Claim 16 is drawn to a gene construct comprising a polynucleotide encoding the recombinant antigen according to claim 12.
Claim 17 is drawn to a recombinant vector comprising the gene construct according to claim 16.
Claim 18 is drawn to a vaccine composition comprising the recombinant antigen according to claim 12.
Further limitations on the vaccine composition according to claim 18 are wherein the vaccine composition has a SARS-CoV-2 specific neutralizing ability (claim 19); wherein the vaccine composition is for preventing or treating SARS-CoV-2 infection (claim 20; NB: the intended use of claim 20, namely “for preventing or treating SARS CoV-2 infection”, does not structurally distinguish the vaccine composition from any composition comprising the claimed recombinant fusion protein antigen, and will not be read as a further limitation into this claim).
Claim 21 is drawn to a method for producing a SARS-CoV-2 recombinant antigen comprising: a step of identifying the gene or amino acid sequence of an immunogenic SARS-CoV-2 RBD; a step of identifying a cell membrane permeation domain comprising a polypeptide selected from the group consisting of SEQ ID NOs: 1 to 22 derived from human LRRC24; a step of preparing the SARS-CoV-2 recombinant antigen by engineering both the immunogenic SARS CoV-2 RBD and the cell membrane permeation domain together as a fusion protein in an expression system, wherein said expression system is designed to overexpress said fusion protein in human cells; and a step of purifying the SARS-CoV-2 recombinant antigen.
Claim 22 is drawn to a kit for preventing or treating SARS-CoV-2 infection comprising a vaccine composition and instructions for use, the vaccine composition comprising a recombinant antigen comprising a cell membrane permeation domain comprising a polypeptide selected from the group consisting of SEQ ID NOs: 1 to 22 derived from human LRRC24 and a SARS-CoV-2 RBD. NB: the intended use of claim 22, namely “for preventing or treating SARS CoV-2 infection”, does not structurally distinguish the kit or compositions therein from any composition comprising the claimed recombinant fusion protein antigen, and will not be read as a further limitation into this claim).
Claim Rejections - 35 USC § 112(a); First Paragraph
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
(Rejection withdrawn.) The rejection of Claims 12-23 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, is withdrawn in light of the amendments to the claims.
(Rejection withdrawn.) The rejection of Claims 12-23 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, is withdrawn in light of the amendments to the claims.
Claim Rejections - 35 USC § 102
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
(Rejection withdrawn.) The rejection of Claims 12-14 and 16-23 under 35 U.S.C. 102(a)(2) as being anticipated by Kulp et. al. (US20230149535A1, Priority 04/11/2020, hereafter “Kulp”) is withdrawn in light of the amendments to the claims.
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.
(New rejection – necessitated by amendment.) Claims 12 and 14-22 are rejected under 35 U.S.C. 103 as being unpatentable over Akahata et. al. (US20210322541A1, priority 04/17/2020; hereafter “Akahata”) and Numata et. al. (US20150218569A1, Pub. 08/06/2015; hereafter “Numata”), in view of Wrapp D, et. al. Science. 2020 Mar 13;367(6483):1260-1263. Epub 2020 Feb 19.; hereafter “Wrapp”.)
The Prior Art
Akahata teaches a polypeptide comprising a coronavirus (CoV) protein fused to a signal sequence and/or transmembrane domain, wherein the coronavirus protein may be the receptor binding domain (RBD) of the S1 subunit of coronavirus spike (S) protein (entire document; see abstract.) Akahata teaches the SARS CoV-2 RBD sequence of SEQ ID NO: 3, which aligns with 100% identity to amino acids 25-228 of instant SEQ ID NO: 24 (see alignment below). Akahata teaches that the RBD may be fused to a transmembrane protein (¶[0013][0039-0040]), such as a leucine-rich repeat (LRR) containing transmembrane protein (¶[0041]). Akahata teaches that SARS CoV-2 S protein sequences and mutants or variants thereof are known in the art, and the Wrapp citation teaches a SARS CoV-2 S protein sequence which comprises the sequence of SEQ ID NO:24 at 100% identity (signal sequence of S protein along with RBD of S protein)(¶[0037] of Akahata; Fig. S5 of Wrapp; instant claim 14.)
Query Match 100.0%; Score 1112; DB 1; Length 247;
Best Local Similarity 100.0%;
Matches 204; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 VRFPNITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTK 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 25 VRFPNITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTK 84
Qy 61 LNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVG 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 85 LNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVG 144
Qy 121 GNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQ 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 145 GNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQ 204
Qy 181 PYRVVVLSFELLHAPATVCGPKKS 204
||||||||||||||||||||||||
Db 205 PYRVVVLSFELLHAPATVCGPKKS 228
Akahata teaches that the protein may be encoded from a recombinant vector (¶[0072-0080]; instant claims 16-17), and that vaccine compositions may comprise the vector, peptide, or polynucleotide encoding said protein (¶[0016][0189-0190]; instant claim 18), wherein said vaccine would be used for raising neutralizing antibody responses useful for prophylactic and/or therapeutic treatment of a SARS CoV-2 infection (¶[0002][0016-0017][0099][0141-163]; Figs. 4-7; instant claims 19-20). Akahata teaches identification of the SARS CoV-2 RBD (¶[0037-0038][0163]), engineering the RBD to a heterologous transmembrane domain (Example 1 at ¶[0101]), Example 2 at ¶[0107]), and then expressing and isolating the resulting recombinant protein (Examples 3-5 at ¶[0124-0140]).
While Akahata teaches the majority of the instant claims, and teaches that the SARS CoV-2 S protein RBD would be fused to a heterologous transmembrane (TM) domain, such as a leucine-rich repeat (LRR) containing transmembrane protein, Akahata fails to teach the specific sequences for the LRR-protein-derived transmembrane domains as outlined in SEQ ID NOs: 1-22. However, such sequences were known in the art, as evidenced by the teachings of Numata.
Numata teaches cell-penetrating sequences derived from LRR proteins (entire document; see abstract.) Numata teaches cell-penetrating peptides (CPPs), which have a function of transporting a complex comprising the peptide and another substance (for example, a protein and a nucleic acid) through biomembrane of mammalian and human cell strains (¶[0004]). Numata teaches the polycationic CPPs can comprise a combination of R, K, and/or H residues (¶[0054-0055]), and that said peptides can be fused to the N- or C-terminus of the cargo to be delivered (¶[0056]). Numata specifically notes “polycationic sequence comprises lysine, arginine and/or histidine residues of preferably 4 or more, more preferably 5 or more and further preferably 7 or more; and preferably 30 or less, more preferably 25 or less and further preferably 20 or less. Furthermore, the polycationic sequence preferably has a continuous series of 3 or more residues of lysine, arginine and/or histidine residue, more preferably, a continuous series of 5 or more residues of lysine, arginine and/or histidine and particularly preferably a continuous series of 7 or more residues of lysine, arginine and/or histidine residue.”(¶[0054]). SEQ ID NO: 32 comprises a CPP that comprises instant SEQ ID NO: 7 at 100% identity.
Given what was known in the art at the time of filing, a skilled artisan would be apprised as to the rationale for generating RBD fused to heterologous TM domains, as taught by Akahata, which is to generate a therapeutic or prophylactic immune response without stimulating antibody-dependent enhancement (ADE) in the host to worsen COVID-related disease (¶[0007-0009]). Given that sequences for SARS CoV-2 S proteins and RBDs were known in the art, as evidenced by the teachings of Wrapp and Akahata, one of skill in the art would be apprised as to such RBD sequences which comprised SEQ ID NO: 24. Given that LRR cell penetrating peptides (CPPs) were known in the art, as evidenced by both Akahata and Numata, and could aid in the generation of an immune response without promoting ADE, as evidenced by the teachings of Akahata, one of skill in the art would be apprised as to the usefulness of fusing the SARS CoV-2 RBD to a TM domain, such as a LRR CPP. Effective LRR CPP sequences were known in the art, as evidenced by the teachings of Numata. Therefore, arriving at the limitations of instant claims 12, 15, and 21-22 would be obvious to a skilled artisan, given the combined teachings of Akahata, Numata, and Wrapp.
It would have been obvious to one of ordinary skill in the art to modify the methods and compositions taught by Akahata in order to utilize other known TM domains, such as LRR CPPs, thereby generating a fusion peptide of SARS CoV-2 RBD and CPP that would be less likely to induce ADE in a subject. One would have been motivated to do so, given the suggestion by Numata that CPP sequences were known or could be generated. There would have been a reasonable expectation of success, given the knowledge that the RBD-CPP fusion proteins were useful in immunogenic compositions, as taught by Akahata, and also given the knowledge that RBD sequences were known in the art, as taught by Akahata and Wrapp. 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.
Double Patenting
The text regarding nonstatutory double patenting was presented in a previous Office action.
(Rejection withdrawn.) The rejection of Claims 12-23 on the ground of nonstatutory double patenting as being unpatentable over claims 2-5 of U.S. Patent No. 12,202,876 in view of Kulp (supra) is withdrawn in light of the amendments to the claims.
(New rejection – necessitated by amendment.) Claims 12 and 14-22 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 2-5 of U.S. Patent No. 12,202,876 in view of Akahata and Wrapp (supra). While the claims are not identical, they are not patentably distinct in that both claims are drawn to recombinant proteins having improved cell membrane permeability, comprising a cargo fused to the N-terminal or C-terminal of the transmembrane domain of the human LRRC24 protein of SEQ ID NOs: 1-7, 21, and 22 (which appear to be identical between claim sets). Both claim the cargo may be a protein, such as a viral protein, and that said fusion protein may be present as a nucleic acid. While the ‘876 claims do not provide that the viral protein is an antigenic protein from SARS CoV-2, such a protein sequence would be obvious given the teachings of Akahata and Wrapp. Since Akahata and Wrapp teach the known SARS CoV-2 protein sequences, such as S protein sequences, domains, and fragments thereof, and the ‘876 provides for the specific LRRC24 cell permeating domains, arriving at the fusion proteins combining both sequences would be obvious to a skilled artisan, especially given the teachings of Akahata, as Akahata teaches the fusion of SARS CoV-2 to heterologous LRR domains. One of skill would find it obvious how to make and use such a protein, especially for raising an immune response against SARS CoV-2, especially in light of the teachings of Akahata and Wrapp. Therefore, the instant claims and the reference ‘876 claims are obvious variants in light of Akahata and Wrapp and are not patentably distinct.
Response to Arguments
Applicant’s arguments with respect to the rejection of the claims under NSDP over the ‘876 patent in view of Kulp have been fully considered and are persuasive in light of the amendments to the claims. Therefore, the rejection has been withdrawn. However, upon further consideration, new grounds of rejection are made in view of Akahata and Wrapp.
For the reasons outlined supra, the instant claims and the ‘876 claims are still obvious variants of one another, and are not patentably distinct.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RACHEL B GILL whose telephone number is (571)272-3129. The examiner can normally be reached on M to F 8:00 AM to 5:00 PM Eastern.
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/RACHEL B GILL/
Primary Examiner, Art Unit 1671