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 Claims
The amended claims filed 04/08/2026 are acknowledged and entered.
Claims 76, 88 have been amended
Claims 1-75, 78-79 are cancelled
Claims 77, 80-84, 86, 87, 92, and 93 are withdrawn.
Claims 76, 85, 88-91 are pending and examined on their merits.
(Claim 86 is included in Group I (see requirement for restriction office action dated 08/19/2025) and thus belongs to a non-elected invention. Therefore, it was not examined as per the list of the claims to be examined in the election restriction requirement section of the 01/08/2016 Non-final action.)
Information Disclosure Statement
Two information disclosure statements (IDS) submitted on 01/08/2006 are being considered by the examiner.
Response to Amendment
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office Action.
Request For Examination of Claims 80-83 and 86-87
Applicant’s arguments have been fully considered and are not persuasive. Therefore, the request is not granted.
Applicant’s Arguments:
- (a) Claims 79-83, 86, and 87 were part of "Group II" in the Restriction Requirement mailed on August 19, 2025, Page 4.
- (b) By the foregoing amendments, the content of Claim 79 has been added to independent Claim 76. Because Claims 80-83 and 85-87 depend from Claim 76 (either directly (Claims 80-83 and 85) or indirectly (Claims 86 and 87)), because Claims 79-83, 86, and 87 were part of Group II, and because the content of Claim 79 is now part of Claim 76, Applicants respectfully request that Claims 80-83 and 85-87 be added to the claims being examined.
Examiner’s Response to Applicant’s arguments: Applicant’s arguments have been carefully considered but are not found persuasive.
- Regarding item (a): Claims 79 (currently cancelled), 80-83, 86, and 87 were never part of Group II but part of Group I. Separate inventions are determined by law (37 CFR 1.475 (a)-(e), 35 U.S.C. 121, 372 and 1.499 and PCT Rule 13.1 and others) and not by applicant’s desire to combine inventions. In addition, applicant’s transversal to the restriction requirement found in the Non-Final Action dated 01/08/2026 was considered and not found persuasive. The restriction was proper and made final.
As a reminder, Groups I, II, III and IV are drawn to different products, regardless of claim dependency. Groups V is drawn to a method, regardless of claim dependency. Applicant arguments do not contest the teaching of the reference(s) cited to establish a lack of unity for Group V.
The elected invention was Group II and the one elected species being CD40.N2.RBDv.
The restriction requirement among the linked inventions (Groups I, II and II) was subject to the nonallowance of the linking claim(s), claims 76, 85, and 91. Upon the indication of allowability of the linking claim(s), the restriction requirement as to the linked inventions shall be withdrawn and any claim(s) depending from or otherwise requiring all the limitations of the allowable linking claim(s) will be rejoined and fully examined for patentability in accordance with 37 CFR 1.104. Claims that require all the limitations of an allowable linking claim will be entered as a matter of right if the amendment is presented prior to final rejection or allowance, whichever is earlier. Amendments submitted after final rejection are governed by 37 CFR 1.116; amendments submitted after allowance are governed by 37 CFR 1.312.
Claims 77, 80-83 and 86-87, as written, still belong to the non-elected group I as they read only on the IG domain being an anti-CD40 antibody, which the exception of claim 79, now cancelled. Claims 77, 80-83 and 86-87 are considered withdrawn because of belonging to an non-elected invention. Withdrawn claims are not examined on the merits at the time of writing of the Office action”.
- Regarding item (b) The amended claim 76 recites: a conjugate wherein a heterologous polypeptide is conjugated or fused to (1) a polypeptide (Npep2) that derives from protein N of SARS-CoV-2 and that consists of an amino acid sequence having at least 95% identity with the amino acid sequence that ranges from the residue at position 276 to the residue at position 411 in SEQ ID NO:2, wherein the conjugate further comprises (2) a receptor binding domain (RBD) polypeptide and wherein the heterologous polypeptide is an (3) immunoglobulin domain.
Claim 76 reads now on Group II as Group II is defined as a conjugate wherein a (1) heterologous polypeptide is fused to a polypeptide (Npep2) from the SARS-CoV-2 N protein and (2) a Receptor Binding domain (RBD) and (3) a CD40 antibody (which is an immunoglobulin) defined either by the heavy chain fused only to the RBD polypeptide and by the light chain fused only to Npep2 polypeptide or by the heavy chain fused only to Npep2 polypeptide and by the light chain fused only to RBD polypeptide (see Non Final Action page 4). Since the elected species is CD40.N2.RBDv, the CD40 antibody is an immunoglobulin domain (heterologous protein) with the heavy chain fused only to the RBD and the light chain is fused only to Npep2. Considering the broadest reasonable interpretation (BRI) of claim 76, as currently written, the heavy chain of the immunoglobulin can be fused to the RBD and the light chain of the immunoglobulin can be interpreted to be the heterologous peptide (an immunoglobulin domain) fused to Npep2. The amended claim 76 recites now the limitations of the elected species, CD40.N2.RBDv, recited in claim 88 (Group II). Claim 76 no longer reads on the unelected Group I as Group I is defined as a heterologous polypeptide fused to a) a polypeptide from the SARS-CoV-2 S protein (at least Npep2 but can further comprise Spep1 and Spep4), wherein the heterologous polypeptide is an immunoglobulin domain (heavy or a light chain, from a CD40 antibody) defined by its CDRs or by the heavy and light chains amino acid sequences. Group I does not specifically recite the RBD as part of the conjugate and claim 76 does not define the immunoglobulin by their CDRs or by the heavy and light chains, therefore the amended claim 76 is no longer linking Groups I-III. Since claims 85 and 91 depend on claim 76 (no longer a linking claim), they are also no longer linking claims for Groups I-III but they read on Group II only.
Claims 77, 79-83 and 86-87 remain withdrawn as belonging to Group I (they read on the heterologous polypeptide being an immunoglobulin domain defined by its CDRs and not by the RBD being part of the conjugate). As mentioned above, Groups I, II, III and IV are drawn to different products, regardless of claim dependency.
Applicant argues as set forth above. Thus, for the reasons set forth above and the reasons of record, this request for examination of claims 80-83 and 86-87 is not granted.
Objections
Specification and Claims - Withdrawn
The disclosure was objected to because of the following informalities:
a) Abstract of the disclosure is objected to because of implied phraseology,
b) The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code.
c) Claims 76 and 88 are objected to because of the following informalities: Abbreviations, acronyms and names should be enclosed within parentheses only.
Applicant has corrected the informalities in the substitute specification and the objection is withdrawn.
Claim Rejections - 35 USC § 112 withdrawn
The rejections for 76, 85, 88 and 90 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph as being indefinite is withdrawn in view of applicant’s amendments of claims 76, 78 and 85 (Npep2, antecedent basis, heterologous peptide, CD40.N2.RBDv, and RBD).
Claim Rejections - 35 USC § 101 - Withdrawn
The rejection of claims 76 and 85 under 35 U.S.C. 101 because the claims recite “nature-based products” as a limiting element or step without having markedly different characteristics than the nature-based product itself is withdrawn in view of Applicant’s amendment of claim 76.
Rejections Maintained
Claim Rejections - 35 USC § 112 Written description – maintained
Claims 76, 85, 88-91 remain rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with (a) the written description requirement.
Applicant’s arguments have been fully considered and are not persuasive. Therefore, the rejections are maintained.
Applicant’s Arguments:
- Applicant amended claim 76 to recite that “…Npep2 that derives from protein N of SARS-CoV-2 and that consists of an amino acid sequence having at least 95% identity with the amino acid sequence that ranges from the residue at position 276 to the residue at position 411 in SEQ ID NO:2….”. Accordingly, only a few amino acids (at most 6) can be mutated, and one of ordinary skill in the art would have known that such variants would remain immunogenic. Moreover, the content of Claim 79, i.e., a claim not rejected for lack of written description under 35 U.S.C. § 112(a), was added to Claim 76 (from which Claims 85 and 88-91 depend, either directly or indirectly).
Examiner’s Response to Applicant’s arguments: Applicant’s arguments have been carefully considered but are not found persuasive.
- Applicant argues that the artisan would have known that up to 6 mutation in the Npep2 are possible, (despite not knowing which would be those 6 mutations and where they are found, or if the 6 mutations would be found sequentially or dispersed throughout the amino acid sequence, be a deletion or an insertion etc.) and still be immunogenic. The specification defines mutation as follows: “As used herein, the term "mutation" has its general meaning in the art and refers to a substitution, deletion or insertion. In particular, the term "substitution" means that a specific amino acid residue at a specific position is removed and another amino acid residue is inserted into the same position. Within the specification, the mutation are references according to the standard mutation nomenclature. In particular the term "mutation" encompasses "naturally-occurring mutations" and "non-naturally occurring mutations" (page 4, line 25). Applicant does not provide any reason as to why the artisan would have known that up to 6 mutations are possible because in fact, artisan cannot know because the mutations are undefined. Applicant still has only provided one species, the elected CD40.N2.RBDv and not any variant with up to 6 mutations in the Npep2. In addition and as discussed in great detail above, Claim 79 could never have been examined as it is withdrawn as pertaining to a non-elected invention. Again, the restriction was deemed proper and made final and it is not up to the applicant to determine which claims are to be examined or decide that, if a non-elected claim is not found in a rejection, it is because the non-elected claim “overcomes a rejection”. Therefore this argument is moot and inconsequential. Last, the limitation of claim 79 now present in 76, does not remedy the fact that the mutations in claim 76 are not defined in such a way that the artisan would have known which Npep2 variant remains immunogenic despite the mutations. For the reasons discussed above and the reasons cited in the Non Final action, the inventor(s), at the time the application was filed, did not have possession of the claimed invention.
Applicant argues as set forth above. Thus, for the reasons set forth above and the reasons of record, the rejection is maintained.
Claim Rejections - 35 USC § 112 Enablement – maintained
Claims 76, 85, 88-91 remain rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with (a) the enablement requirement.
Applicant’s arguments have been fully considered and are not persuasive. Therefore, the rejections are maintained.
Applicant’s Arguments:
- Applicant amended claim 76 to recite that “…Npep2 that derives from protein N of SARS-CoV-2 and that consists of an amino acid sequence having at least 95% identity with the amino acid sequence that ranges from the residue at position 276 to the residue at position 411 in SEQ ID NO:2….”. Accordingly, only a few amino acids (at most 6) can be mutated, and one of ordinary skill in the art would have known that such variants would remain immunogenic. Moreover, the content of Claim 79, i.e., a claim not rejected for lack of written description under 35 U.S.C. § 112(a), was added to Claim 76 (from which Claims 85 and 88-91 depend, either directly or indirectly).
Examiner’s Response to Applicant’s arguments: Applicant’s arguments have been carefully considered but are not found persuasive.
- Applicant argues that the artisan would have known that up to 6 mutation in the Npep2 are possible, despite not knowing which would be those 6 mutations and where they are found, or if the 6 mutations would be found sequentially or dispersed throughout the amino acid sequence, be a deletion or an insertion etc. and still be immunogenic. The specification defines mutation as follows: “As used herein, the term "mutation" has its general meaning in the art and refers to a substitution, deletion or insertion. In particular, the term "substitution" means that a specific amino acid residue at a specific position is removed and another amino acid residue is inserted into the same position. Within the specification, the mutation are references according to the standard mutation nomenclature. In particular the term "mutation" encompasses "naturally-occurring mutations" and "non-naturally occurring mutations" (page 4, line 25). Applicant does not provide any reason as to why the artisan would have known that these mutations are enabled and retained the immunogenic function. The only way for an artisan to know would be to be told what and where these mutations are. But the specification does not provide a clear define structure for all the variant Npep2s, thus, the mutations are undefined. Applicant still has only provided one species, the elected CD40.N2.RBDv and not variants thereof with up to 6 mutations in the Npep2. In addition and as discussed in great detail above, Claim 79 is withdrawn as pertaining to a non-elected invention and Therefore this argument is moot and inconsequential. Last, the limitation of claim 79 now present in 76, does not remedy the fact that the mutations in claim 76 are not defined in such a way that the artisan would have known which Npep2 variant remains immunogenic (despite the mutations) without undue experimentation. For the reasons discussed above and the reasons cited in the Non Final action, it would require undue experimentation for one skilled in the art to use the claimed invention.
Applicant argues as set forth above. Thus, for the reasons set forth above and the reasons of record, the rejection is maintained.
Claim Rejections - 35 USC § 103 - Maintained
Claims 76, 85, 88, and 91 are rejected under 35 U.S.C. 103 as being unpatentable over Hashem (previously cited), Grifoni (previously cited), and QIA98613.1 (previously cited) in view of Zurawski1 (previously cited), Zurawski2 (previously cited), Flamar (previously cited), AJD85779.1 (previously cited) and AJD85780.1 (previously cited).
Applicant renamed each of the GenBank accession numbers as the name of the respective authors, Yeh refers to QIA98613.1, Flamar2 refers to AJD85779.1 and Flamar3 refers to AJD85780.1. Only the sequences of the GenBank accession numbers were used as prior art for the rejection.
Applicant’s arguments have been fully considered and are not persuasive. Therefore, the rejection is maintained.
Applicant’s Arguments:
- (a) At the outset, Applicants wish to highlight that Claim 76, from which Claims 85, 88, and 91 depend (either directly or indirectly), has been amended to include the content of Claim 79, i.e., a claim not rejected under 35 U.S.C. § 103 due to Hashem, Grifoni, QIA98613.1, Zurawski1, Zurawski2, Flamar and AJD85780.1. That alone evidences that the rejections under 35 U.S.C. § 103 should be withdrawn.
Examiner’s Response to Applicant’s arguments:
The Applicant’s arguments with respect to claim 79 has been considered but are moot because the limitations added to claim 76 to require that the heterologous polypeptide is an immunoglobulin domain is taught by Hashem.
Applicant argues as set forth above. Thus, for the reasons set forth above and the reasons of record, the rejection is maintained.
Applicant’s Arguments:
- (b) TRIMERIZATION MOTIF. Hashem mentions a vaccine comprising a MERS-CoV S1 protein (including antigens of proteins S (including RBD), E, M, and N (nucleocapsid)) fused to a CD40 ligand polypeptide, which may be CD40L or antibodies or antibody fragments that activate or agonize CD40, and that incorporating a CD40 ligand into a MERS-CoV S1 subunit vaccine can enhance immunogenicity. Hashem thus differs from Claim 76 by the specific antigen used (Npep2). In addition, the conjugates of Hashem not only contain a MERS antigen and a CD40 ligand but also at least one trimerization motif. Applicant argues then that the trimerization motif is an essential feature of Hashem’s invention such that one of ordinary skill in the art would be deterred from using conjugates without such a trimerization motif.
Examiner’s Response to Applicant’s arguments: The trimerization motif is found in the context of the S protein and the CD40L ([0061-0062], Fig 2-3, 4A)., which makes sense because the spike protein is a trimer. Applicant also defines the S protein as a trimer in the specification (page 8, line 16). In addition Hashem in [0062] teaches that the trimerization motif facilitates trimerization of S or S1 and/or CD40L may be, respectively, omitted as monomeric or dimeric forms of S protein can exhibit immunological activity and monomeric or dimeric forms of CD40L can bind to CD40. If the motif can be omitted, this teaching is in direct contradiction with applicant’s argument that the motif is “an essential feature” of Hashem’s invention. That being said, neither the spike protein nor the CD40L are limitations found in the elected Group II invention or as part of the elected CD40.N2.RBDv construct species and non-elected inventions are not part of the examination, Prior art teachings outside the scope of Group II claims are moot because limitations from the specification are not read into the claims. Group II limitations are drawn to a nucleocapsid (variant) and an immunoglobulin (CD40 antibody) which, and confirmed by applicant above (see bold), are found in the teachings of Hashem as discussed in the Non Final action submitted on 01/08/2026.
Moreover, the transitional term “comprising” found in claim 76, which is synonymous with “including,” “containing,” or “characterized by,” is inclusive or open-ended and does not exclude additional, unrecited elements or method steps. See, e.g., > Mars Inc. v. H.J. Heinz Co., 377 F.3d 1369, 1376, 71 USPQ2d 1837, 1843 (Fed. Cir. 2004).
Applicant argues as set forth above. Thus, for the reasons set forth above and the reasons of record, the rejection is maintained.
Applicant’s Arguments:
- (c) While Zurawski, Zurawski 2, and Flamar discuss vaccines comprising a CD40 antibody attached to HA antigen, HIV Env gp140, or other HIV antigens at the C-terminus of its heavy chain, these conjugates contain antigens from viruses that are not coronaviruses, and one of ordinary skill in the art would not have reasonably expected obtaining a strong response when using a coronavirus antigen, in particular in view of the teaching in Hashem that the conjugate should contain at least one trimerization motif. In addition, Npep2 as now defined narrowly in Claim 76 (specific portion corresponding to amino acids 276 to 411, or variants with at least 95% identity) is not any alternative antigen.
Examiner’s Response to Applicant’s arguments: Applicant’s arguments have been carefully considered but are not found persuasive.
One cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Whereas (1) Hashem teaches a vaccine comprising a MERS-CoV antigen (which includes the nucleocapsid) fused to a CD40 antibody and that there are several vaccine candidates including RBD protein-based subunit vaccines, (2) Grifoni teaches how to predict B- and T-cell epitopes located within the N protein of SARS-CoV-2 one of which encompasses 46 amino acids spanning residues 35-400 (at 91% identity with SEQ ID NO: 2. (3) QIA98613.1 teaches an amino acid sequence that is 100% identical to SEQ ID NO: 2 (see (e) for further discussion on Grifoni and QIA98613.1, (4) Zurawski1 teaches a vaccine composition comprising CD40 antibody attached to a viral antigen attached directly to the Heavy Chain (HC) C terminus. (5) Zurawski2 teaches dendritic cells-targeting vaccines comprising antibodies to CD40 (fused to HIV antigens (that is, viral antigens) and these vaccines raised robust immunity against HIV-1. HIV Env gp140 protein is fused to the C-terminus of the CD40 antibody HC (6) Flamar teaches specifically the 12E12 CD40 antibody and their vaccine expands memory CD4+ and CD8+ T cells (motivation to combine) and (7) AJD85779.1 and AJD85780.1 teach the sequences of the 12E12 antibody which are 100% identical to instant SEQ ID NO: 35 (VH of 12E12) (AJD85779.1) and 100% identical to instant SEQ ID NO: 36 (VL of 12E12) (AJD85779.1). All these references address the many limitations found in the instant claims 76, 85, 88, and 91 and the motivation to combined all these references.
Applicant has not sufficiently described why there is no prima facie case for obviousness.
Applicant has not addressed any disagreement with the motivation to combine the references.
Applicant has not offered any explanation as to why one of ordinary skill in the art would not have reasonably expected obtaining a strong response when using a coronavirus antigen. Coronavirus antigens are known to be immunogenic and Grifoni is able to predict T- and B-cells epitopes located within the N protein of SARS-CoV-2. In addition, CD40 antibodies expands memory CD4+ and CD8+ T cells (Flamar) increasing the immune response.
The teachings of Hashem have been discussed above.
Regarding the amendments to claim 76 please see item (e) below.
See discussion in the Non Final Action submitted on 01/08/29026 for more details regarding the teachings of the prior art relevant to the rejection under 35 U.S.C. 103 and the motivation to combine these references.
Applicant argues as set forth above. Thus, for the reasons set forth above and the reasons of record, the rejection is maintained.
Applicant’s Arguments:
- (d) Technical data presented in Applicants' Specification show that:
- Several constructs (Gen2a, Gen2b, and Gen2c) in which Npep2 is fused
to the heavy or light chain of an anti-CD40 antibody in various configurations are able to expand polyfunctional SARS-CoV-2-specific CD4+ T cells in SARS-CoV- 2-infected convalescent donor PBMC cultures (see Figure 3 and Figure 5 for Gen2a).
- In addition, some of the generated CD4+ T cells are specific of Npep2 presented epitopes (see peptide pools 2, 3, 4 in Figure 3 and "Npep2" in Figure 5.
- Therefore, Npep2 clearly generates an expansion of polyfunctional SARS CoV2-specific CD4+ T cells response when incorporated in various constructs. Therefore, based on Applicants' Specification as filed, one of ordinary skill in the art would have concluded that Npep2 is a truly immunogenic peptide, which is capable of inducing polyfunctional T cells responses.
- Applicants' Specification: the inventors specifically selected not only SARS-Cov2 proteins regions containing B- and T-cells epitopes, but also that corresponded to conserved regions between different coronavirus, and also contained described B, CD8 and CD4 SARS-CoV-1 epitopes. The inventors not only aimed at generating a vaccine inducing a response against SARS-Cov-2, but more generally a vaccine inducing a response against various beta-coronaviruses, including both SARS-Cov-1 and SARS-Cov-2.
- Applicant’s discussion of the teachings of Coleon. Involved polyfunctional T cell responses of non-elected species; cross-reactive nature of selected peptides; Npep2 being adapted for pansarbecorvirus vaccination.
- Applicant’s discussion of the teachings of Nguema includes a non-elected species capable of establishing long-term immunity and induction spike and nucleocapsid specific CD8+ progenitors with stem-cell like memory.
In summary, the inventors have identified a unique fragment of SARS-Cov2 N protein that, when used as an immunogen, is able to confer long-term protection against not only the specific strain of SARS-Cov2 used for defining Npep2 sequence, but also variants of this strain and even other sarbecoviruses, including bat or pangolin sarbecoviruses that might one day infect humans. This was neither disclosed nor suggested by the cited art. In particular, none of the cited documents discloses or suggests that it would be possible to find a peptide that would be able to confer an immunity that would be both long-lasting and cross- reactive to many other sarbecoviruses.
Examiner’s Response to Applicant’s arguments: Applicant’s arguments have been carefully considered but are not found persuasive.
Applicants are reminded that any arguments pertaining to non-elected claims or non-elected species will not be addressed in this Final Office Action, because these limitations are withdrawn from consideration subsequence to applicant’s response to the Lack of Unity mailed on 11/19/2025.
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 (all the points claimed above (including (1) a fragment of SARS-Cov2 N protein that, when used as an immunogen, (2) is able to confer long-term protection against not only the specific strain of SARS-Cov2 used for (3) defining Npep2 sequence, but also variants of this strain and even other (3) sarbecoviruses, including bat or pangolin sarbecoviruses, .etc.) 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).
Applicant argues as set forth above. Thus, for the reasons set forth above and the reasons of record, the rejection is maintained.
Applicant’s Arguments:
- (e) Grifoni indicates that publicly-available resources were used to predict B- and T-
cell epitopes located within the S and N protein of SARS-CoV-2. However, Grifoni does not report any experimental data showing that any peptide derived from SARS-Cov2 N protein, let alone one corresponding to Npep2 as now claimed, is indeed able to confer an immunity that would be both long-lasting and cross-reactive to many other sarbecoviruses. In addition, Grifoni does not specifically point to Npep2 as now claimed. In contrast, in order to confer an immunity that would be both long-lasting and cross-reactive to many other sarbecoviruses, Grifoni would have motivated one of ordinary skill in the art to incorporate other SARS-Cov2 peptides.
Yeh indicates the amino acid sequence of SARS-Cov2 N entire protein, but does
not disclose or suggest selecting the particular region from amino acids 276 to 411
corresponding to Npep2.
Flamar 2 and Flamar 3 mention the sequences of the 12E12 antibody, but do
not teach anything about the particular region from amino acids 276 to 411
corresponding to Npep2. The issue is not whether one with ordinary skill in the art "could" have arrived at the claimed invention, but instead whether one of ordinary skill in the art - without
hindsight based on the claimed invention - would have reason to do so.
Examiner’s Response to Applicant’s arguments:
As mentioned above, applicants are reminded that any arguments pertaining to non-elected claims or non-elected species will not be addressed in this Final Office Action, because these limitations are withdrawn from consideration subsequence to applicant’s response to the Lack of Unity mailed on 11/19/2025.
One cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references (see explanation above). For example: Grifoni and Yeh in combination teach Npep2. Grifoni identifies the area of the N protein (the S protein is not a limitation of the claims of the elected Group II) with predicted B- and T-cell epitopes, one of which encompasses 46 amino acids spanning residues 35-400. Yeh teaches the N protein (SEQ ID NO; 2 and therefore it would be obvious that a longer fragment would be based on the N protein sequence taught by Yeh. Claim 76 has been amended and the limitation “comprising at least 50 consecutive amino acids” is no longer required for Npep2, instead Npep2 is now defined as an amino acid sequence 276-411 (135 amino acids of SEQ ID NO; 2) having at least 95% identity. An alignment between of the instant SEQ ID NO:7 (Npep2 (the first 138 amino acids from 276 to 413) and RBD) and the Yeh sequences shows 99.3% of identity (compared to 95% as required by instant claim 76). If we only look exactly at the amino acid sequence from 276 to 411 (that is, amino acids 412 and 413 are excluded) is 100% identity. See below:
Title: US-17-927-804-7
Sequence: 1 RRGPEQTQGNFGDQELIRQG..........ATVCGPKKSTNLVKNKSVNF 361
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342
686
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Greyscale
It would be obvious for a person of ordinary skill in the art to use the amino sequence from 276 to 411 taught by Yeh as Grifoni teaches predicted B- and T-cell epitopes, one of which encompasses 46 amino acids spanning residues 35-400. It would further be obvious with that the length of a fragment in a sequence is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ. It would have been customary for an artisan of ordinary skill to determine the optimal fragment length. The principle of law states from MPEP 2144.05: "The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages." (Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382); Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 2.
In this case, the amended claim 76 currently defines Npep2 as deriving from protein N of SARS-CoV-2 and that consists of an amino acid sequence having at least 95% identity with the amino acid sequence that ranges from the residue at position 276 to the residue at position 411 in SEQ ID NO:2. The combination of Yeh and Grifoni teach the current definition of Npep2. Flamar 2 and Flamar 3 teach the 12E12 (CD40) antibody, but they are not required to teach anything regarding any Npep2 limitations as these limitations are taught by Grifoni and Yeh. The elected species, CD40.N2.RBDv, defined in instant claim 88 as the heavy chain of the 12E12 fused to the Npep2 polypeptide and the light chain of the antibody is fused to a receptor binding domain (RBD) polypeptide, was rejected as being obvious by the combination of Hashem (a fusion protein between the N protein and a CD40 antibody, Yeh and Grifoni (the current definition of Npep2 (the N protein being derived from SARS-CoV-2)) and Flamar 2 and Flamar 3 (12E12).
Although the claims are interpreted in light of the specification, limitations from the specification (such as Npep2 conferring an immunity that would be both long-lasting and cross-reactive to many other sarbecoviruses) are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
In response to Applicant’s argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). As discussed above and in the Non Final Action dated 01/06/2026, there is ample motivation to combine the references independent of the inherent feature.
Applicant argues as set forth above. Thus, for the reasons set forth above and the reasons of record, the rejection is maintained.
Applicant’s Arguments:
- (f) The rejections rely upon eight (8) publications. "Obviousness requires
more than a mere showing that the prior art includes separate references covering each
separate limitation in a claim under examination." Unigene Labs., Inc. V. Apotex, Inc.,
655 F.3d 1352, 1360 (Fed. Cir. 2011).
Examiner’s Response to Applicant’s arguments:
In response to applicant's argument that the examiner has combined an excessive number of references, reliance on a large number of references in a rejection does not, without more, weigh against the obviousness of the claimed invention. See In re Gorman, 933 F.2d 982, 18 USPQ2d 1885 (Fed. Cir. 1991).
In this particular case, and based on the format of the 103 rejection written in such a way grouping claims as opposed to rejecting claims individually, 8 references are not an excessive number of reference to cover 4 claims with many limitations, some of these claims having more than 2 limitations. Additionally, 3 of the 8 prior art references (the GenBank accession numbers) are only teaching the sequence needed for the alignments of the claimed SEQ ID NOs.
Applicant argues as set forth above. Thus, for the reasons set forth above and the reasons of record, the rejection is maintained.
Claims 76, 78 (now canceled), 88-90 are rejected under 35 U.S.C. 103 as being unpatentable over Hashem, Grifoni, QIA98613.1, Zurawski1, Zurawski2, Flamar, AJD85779.1 and AJD85780.1 in view of Aurisicchio (previously cited), Naveca (previously cited) and Estep (previously cited).
Applicant renamed each of the GenBank accessions to the respective authors, Yeh refers to QIA98613.1, Flamar2 refers to AJD85779.1 and Flamar3 refers to AJD85780.1. Only the sequences of the GenBank accession numbers were used for the rejection.
Applicant’s arguments have been fully considered and are not persuasive. Therefore, the rejection is maintained.
Applicant’s Arguments:
- (a) The framework for a proper obviousness analysis is set forth above, as are the exemplary deficiencies of Hashem, Grifoni, Yeh, Zurawaski, Zurawski 2, Flamar, Flamar2, and Flamar 3. Because Aurisicchio, Naveca, and Estep fail to remedy those fundamental deficiencies; because Claim 76, from which Claims 88-90 depend (either directly or indirectly), has been amended to include the content of Claim 79, i.e., a claim not rejected under 35 U.S.C. § 103 due to Hashem, Grifoni, Yeh, Zurawaski, Zurawski. 2, Flamar, Flamar 2, Flamar 3, Aurisicchio, Naveca, and Estep; and because reliance upon 11 publications is even more suspect than reliance upon eight publications, the rejections under 35 U.S.C. § 103 should be withdrawn
Examiner’s Response to Applicant’s arguments:
Claim 79 is withdrawn as pertaining to a non-elected invention as discussed above.
In addition, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).See Non Final Action dated 01/06/2026 for more details regarding the teachings of Aurisicchio, Naveca, and Estep relevant to the rejection under 35 U.S.C. 103 and the motivation to combine these references.
In response to applicant's argument that the examiner has combined an excessive number of references, reliance on a large number of references in a rejection does not, without more, weigh against the obviousness of the claimed invention. See In re Gorman, 933 F.2d 982, 18 USPQ2d 1885 (Fed. Cir. 1991). In this particular case the 8 references from the rejection of claim 76 (including claims 85, 88, and 91) are included because 78 (now canceled), depends directly or indirectly from the amended claim 76. The limitations recited only in 78 (now canceled), 88-90 are taught by Aurisicchio, Naveca, and Estep and 3 prior art references are not an excessive or suspect number.
Applicant argues as set forth above. Thus, for the reasons set forth above and the reasons of record, the rejection is maintained.
Double Patenting- Maintained
Claims 76, 85 and 91 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 19-25, 28 and 37 of copending application No. 18/710,734. The reference is not afforded safe harbor protection under 35 USC 121 because it does not share continuity with much less is it subject to a restriction/speciation with the instant application.
Applicant’s arguments have been fully considered and are not persuasive. Therefore, the rejections are maintained.
Applicant’s Arguments:
Prosecution in the '734 Application has not yet begun. Because the content of any claim(s) to issue from the '734 Application is not yet known, any allegation of obviousness type double patenting is premature and should be withdrawn.
Examiner’s Response to Applicant’s arguments: Applicant’s arguments have been carefully considered but are not found persuasive.
Applicant’s request for the withdrawal of the rejection is moot when the rejection is in fact a PROVISIONAL rejection because the patentably indistinct claims have not in fact been patented. Applicants are reminded that a double patenting rejection should be considered if there is a co-pending application or U.S. patent that anticipates or renders obvious the instant invention (see MPEP 804 I. B.). The rejection itself already addresses that the claims are not patented. Therefore, applicant may request that this provisional double patenting rejection be held in abeyance until the claims are otherwise allowable, but such a response would not result in the rejection being withdrawn.
Applicant argues as set forth above. Thus, for the reasons set forth above and the reasons of record, the rejection is maintained.
New Rejections Based on Amendments
Claim Rejections - 35 USC § 112(a)
Claims 76, 85, and 91 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
In making a determination of whether the application complies with the written description requirement of 35 U.S.C. 112, first paragraph, it is necessary to understand what Applicant has possession of and what Applicant is claiming.
Claim 76 recites “the conjugate further comprises a receptor binding domain (RBD) polypeptide and wherein the heteroloqous polypeptide is an immunoqlobulin domain” that is capable of functioning as a vaccine (claim 91)), which encompasses a genus of agents., Claims 85 and 91 are dependent from Claim 76 and do not materially limit the genus of agents, especially regarding the nature of the agent and which immunoglobulin domains would be able to function as a vaccine and are therefore included in the rejection. These claims do not require that the genus of the claims possess any particular immunoglobulin structure or other distinguishing feature that is characteristic of the genus as a whole. Therefore, the claims are drawn to a genus of “conjugates comprising an immunoglobulin which there is inadequate written description.
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 (see MPEP 2163(II)(3)(a)(i)(A), reduction to drawings MPEP 2163(II)(3)(a)(i)(B), 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 MPEP 2163(II)(3)(a)(i)(C).
In the instant case, the only identifying characteristic present in the claim is a recitation of requisite activity (------------------capable of function as a vaccine). The term “immunoglobulin domain" refers to a globular region of an antibody chain (such as e.g. a chain of a conventional 4-chain antibody or of a heavy chain antibody or light chain), or to a polypeptide that essentially consists of such a globular region (Specification page 12, line 30-32), which is a very broad definition comparing antibodies and polypeptides with a globular region. The claims do not identify any particular portion of a structure that must be conserved for said activity. Regarding the genus of the claims the specification describes specific species being CD40 antibodies, in particular, within the genus claimed, 12E12 (the antibody found in the elected species CD40.N2.RBDv: (Specification, page 41 lines 26-53 to page 42 lines 1-2) 12E12 sequence being SEQ ID NOs: 56 and 57. From the specification, it is clear that Applicant is in possession of the conjugate CD40.N2.RBDv (elected species). The claims, however are not limited to that species but also includes any immunoglobulin, and the specification fails to provide a representative number of species within the recited genus. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, or representative number of species, the specification does not provide adequate written description of the claimed genus.
For the reasons discussed above and the reasons cited in the prior Office action, the inventor(s), at the time the application was filed, did not have possession of the claimed 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to IMMA BARRERA whose telephone number is (571) 272-0674. The examiner can normally be reached Monday - Friday 9 to 5.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael Allen can be reached on (571) 270-3497. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/IMMA BARRERA/
Examiner, Art Unit 1671
/BENJAMIN P BLUMEL/Primary Examiner, Art Unit 1671
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