DETAILED ACTION
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 07/16/2026 has been entered.
Disposition of Claims
Claims 1, 7, 9-10, 16, 42, 46, 48, 52, 55-56, 59-60, 63-65, and 67-70 were pending. Claims 2-9, 11-41, 43-45, 47, 49-54, 57-63, and 66 have been cancelled. New claim 71 is acknowledged and entered. Amendments to claims 1, 10, 42, 64-65, and 67-70 are acknowledged and entered. Claims 1, 10, 42, 46, 48, 55-56, 59-60, 64-65, and 67-71 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 US20230165952A1, Published 06/01/2023. Amendments presented to the specification on 10/15/2025 are acknowledged and entered.
Applicant is encouraged to utilize the new web-based Automated Interview Request (AIR) tool for submitting interview requests; more information can be found at https://www.uspto.gov/patent/laws-and-regulations/interview-practice.
The Power of Attorney filed 09/17/2025 is acknowledged and entered.
Response to Arguments
Applicant's arguments filed 07/16/2026 regarding the previous Office action dated 01/16/2026 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 If they have been found to be persuasive, the objection/rejection has been withdrawn below. Likewise, if a rejection/objection has not been recited, said rejection/objection has been withdrawn.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arguments have not been found to be persuasive, or if there are arguments presented over art that has been utilized in withdrawn rejections but utilized in new rejections, the arguments will be addressed fully with the objection/rejection below.
Claim Objections
(Objection withdrawn.) The objection to Claim 9 is withdrawn in light of the cancellation of said claim.
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(Rejection withdrawn). The rejection of Claim 42 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn in light of the cancellation of said claim.
(New rejection.) Claim 1 and dependent claims 10, 42, 46, 48, 55-56, 59-60, 64-65, and 67-71 thereof are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites that “wherein the at least one betacoronavirus epitope comprises or is the receptor binding domain (RBD) of the spike protein or a part of the RBD”. The phrase “a part of the RBD” fails to define the metes and bounds of the claimed antigenic unit. The claim does not specify the minimum length of the recited “part”, the residues that must be present, whether the part must retain receptor-binding function/activity, whether it must remain in a particular conformation, or whether the part itself must constitute an immunologically recognizable epitope.
The specification discloses RBD constructs, including a “RBD long” corresponding to amino acids 319-542, as well as particular RBD-containing vaccine constructs (¶[0508][0126-136]). The specification also repeatedly states more generally that the antigenic unit may comprise “the receptor binding domain of the spike protein or a part thereof” (¶[0281][0438]) but does not provide an objective criterion for determining how much of the RBD constitutes a claimed “part”. As presently written, the limitation could reasonably encompass substantially the entire RBD, a defined subdomain, a peptide containing a B-cell epitope, or potentially a much shorter fragment of the RBD. Because the claim and specification do not provide an objective boundary for determining which RBD fragments satisfy “a part of the RBD”, the scope of the claim is unclear.
Since a skilled artisan would not be reasonably apprised as to the metes and bounds of the claimed invention, instant claim 1 is rejected on the grounds of being indefinite. Claims 10, 42, 46, 48, 55-56, 59-60, 64-65, and 67-71 are also rejected since they depend from claim 1, but do not remedy these deficiencies of claim 1.
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 1 is drawn to a vaccine comprising a pharmaceutically acceptable carrier and an immunologically effective amount of:
a polynucleotide comprising a nucleotide sequence encoding a polypeptide comprising:
a targeting unit;
a dimerization unit; and
an antigenic unit,
wherein the targeting unit interacts with surface molecules on antigen-presenting cells (APCs), wherein the surface molecules are selected from HLA, cluster of differentiation 14 (CD14), cluster of differentiation 40 (CD40), chemokine receptors, and Toll-like receptors, wherein said interaction is capable of leading to internalization of the polypeptide into the antigen-presenting cells, and
wherein the antigenic unit comprises at least one betacoronavirus epitope, wherein the at least one betacoronavirus epitope comprises or is the receptor binding domain (RBD) of the spike protein or a part of the RBD.
Further limitations on the vaccine according to claim 1 are wherein the at least one betacoronavirus epitope comprises or consists of an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO: 231 or SEQ ID NO: 802, or SEQ ID NO: 803 or SEQ ID NO: 804 or SEQ ID NO: 805 (claim 10); wherein said targeting unit comprises antibody binding regions with specificity for said surface molecules on antigen presenting cells (APCs)(claim 42); wherein the targeting unit is human MIP-1alpha (claim 46); wherein the dimerization unit comprises a hinge region, or wherein the dimerization unit comprises a hinge region, another domain that facilitates dimerization, and a dimerization unit linker, which connects the hinge region and the other domain that facilitates dimerization (claim 48); wherein said betacoronavirus is one selected from SARS-CoV, MERS-CoV, SARS-CoV- 2, HCoV-OC43 and HCoV-HKU1 (claim 55); a polynucleotide as defined in claim 1, or a vector comprising a polynucleotide as defined in claim 1 (claim 56); wherein the polynucleotide comprises a nucleotide sequence encoding a polypeptide comprising the amino acid sequence of SEQ ID NO: 233 (amino acid sequence of signal peptide and mature peptide of hMIP1α (LD78b), human hinge region 1 from IgG3, human hinge region 4 from IgG3, glycine-serine linker, human CH3 domain of IgG3 and glycine-leucine linker; claim 67); wherein the polynucleotide comprises a nucleotide sequence encoding a polypeptide comprising the amino acid sequence of SEQ ID NO: 295 (amino acid sequence of VB2129; claim 68); wherein the polynucleotide comprises a nucleotide sequence encoding a polypeptide comprising the amino acid sequence of SEQ ID NO: 255 (amino acid sequence of VB2060; claim 69); wherein the polynucleotide comprises the nucleotide sequence of SEQ ID NO: 294 (nucleotide sequence encoding VB2129) or SEQ ID NO: 254 (nucleotide sequence encoding VB2060; claim 70); and wherein the targeting unit interacts with chemokine receptors selected from C-C motif chemokine receptor 1 (CCR1), C-C motif chemokine receptor 3 (CCR3) and C-C motif chemokine receptor 5 (CCR5)(claim 71).
Claim 64 is drawn to a method for preparing the vaccine according to claim 1, wherein the method comprises:
a) preparing the polynucleotide;
b) optionally cloning the polynucleotide into an expression vector; and
c) mixing the polynucleotide obtained from step a) or the vector obtained from step b) with the pharmaceutically acceptable carrier.
Claim 65 is drawn to a method for treating a subject suffering from a betacoronavirus infection or being in need of prevention thereof, the method comprising administering to the subject the vaccine as defined in claim 1.
Claim Rejections - 35 USC § 112(a); New Rejection
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.
(New rejection.) Claims 1, 10, 42, 55-56, 59-60, 64-65, and 71 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for polynucleotide vaccines and encoded vaccine constructs employing the disclosed MIP-1alpha targeting unit, including targeting through CCR1, CCR3, and CCR5, and the disclosed MHC Class II-directed targeting constructs, does not reasonably provide enablement for the broader genus of targeting units that interact with the claimed APC surface molecules and whose interaction is capable of leading to internalization of the encoded polypeptide into APCs. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
The legal considerations that govern enablement determinations pertaining to undue experimentation have been set forth in In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988). The factors to be considered include: (1) the breadth of the claims; (2) the nature of the invention; (3) the state of the prior art; (4) the level of one of ordinary skill; (5) the level of predictability in the art; (6) the amount of direction provided by the inventor; (7) the existence of working examples; and (8) the quantity of experimentation needed to make or use the invention based on the content of the disclosure. The factors are considered as a whole in determining whether any necessary experimentation would have been undue.
Nature of the invention and breadth of the claims. The claimed invention is directed to a vaccine comprising a pharmaceutically acceptable carrier and an immunologically effective amount of a polynucleotide encoding a polypeptide comprising a targeting unit, a dimerization unit, and a betacoronavirus antigenic unit comprising the RBD or a part thereof, wherein the targeting unit interacts with a recited APC surface molecule and the interaction is capable of leading to internalization of the polypeptide into the APC.
The specification describes vaccine constructs employing MIP-1alpha as the targeting unit, including RBD-containing constructs such as VB2049 and VB2060, and also describes the anti-mouse MHCII scFv-targeted RBD construct VB2059 and the corresponding spike construct VB2071. The constructs were expressed and characterized, and several were tested for antibody and T-cell responses. The specification further reports that MIP-1alpha targeted VB2049 and VB2060 elicited stronger RBD-specific T-cell responses than the anti-mouse MHCII scFV-targeted VB2059 (¶[0575-0608][0641-0647]; Examples 2-3a and 6).
However, claims 1, 10, 42, 55-56, 59-60, 64-65, and 71 are not limited to the disclosed embodiments. Claims 1 and its applicable dependent claims encompass targeting units interacting with HLA, CD14, CD40, chemokine receptors, or Toll-like receptors, provided that the interaction is capable of leading to internalization of the encoded polypeptide into an APC. Claim 42 further encompasses antibody binding regions directed to multiple different APC surface molecules and receptors. Claim 71 narrows the chemokine receptors to CCR1, CCR3, or CCR5, but does not limit the targeting unit to the disclosed MIP-1alpha targeting unit or another defined targeting sequence. Claim 71 therefore continues to encompass structurally different targeting units that interact with one or more of CCR1, CCR3, or CCR5 and produce the claimed internalization function. The claimed scope therefore extends beyond the embodiments described in the specification.
State of the prior art and predictability of the art. At the time the application was filed, it was known that targeting an antigen to different receptors on APCs could alter antigen uptake, intracellular trafficking, degradation, and presentation. Chatterjee et. al. (Chatterjee B, et. al. Blood. 2012 Sep 6;120(10):2011-20. Epub 2012 Jul 12.) compared identical antigens targeted through different dendritic cell receptors. Chatterjee reported that “the receptor least efficient at internalization, CD40, was the most efficient at cross presentation,” and attributed the difference to receptor-dependent uptake and intra-endosomal degradation.
Verma et. al. (Verma A, et. al. mBio. 2018 Feb 27;9(1):e00209-18.) likewise demonstrated that the pathway by which an antigen entered an APC affected the resulting immune response. Receptor binding anthrax protective antigen produced robust total IgG and neutralizing responses, whereas redirecting efficient uptake through the cholera-toxin receptor restored a strong total IgG response but produced a substantially poorer neutralizing response. Verma concluded that the antigen capture pathway can determine both the magnitude and quality of the resulting antibody response.
The prior art further indicates that receptor mediated uptake and subsequent antigen handling were dependent upon the particular receptor and intracellular pathway rather than being a predictable consequence of binding any APC surface molecule. Chatterjee demonstrated markedly different internalization and cross-presentation behavior when the same antigen was directed to different receptors, while Verma demonstrated that efficient uptake through an alternative receptor pathway did not reproduce the immunologic result obtained through the original receptor pathway. The prior art demonstrates that particular APC-targeting molecules directed to several of the recited receptor classes were known and could be incorporated into targeted vaccine constructs. However, the art also does not establish that targeting units directed to the full scope of HLA molecules, chemokine receptors, Toll-like receptors, CD14,and CD40 would uniformly possess the claimed internalization property merely by virtue of binding the recited surface molecule. Accordingly, the known successful use of particular targeting molecules does not provide a general rule by which one skilled in the art could identify, without further empirical testing, the full genus of additional targeting units encompassed by the claims.
Level of skill in the art. One skilled in the art would have been familiar with recombinant DNA construction and protein expression, methods for preparing antibody or ligand based targeting units, and receptor binding and cellular uptake assays. One skilled in the art also would have been capable of evaluating expressed vaccine constructs using standard immunologic assays. However, the existence of known methods for preparing and testing candidate embodiments does not establish that one skilled in the art would have known, without further experimentation, which additional targeting unit sequences and vaccine constructs would satisfy the claimed limitations.
Working examples. The specification provides multiple working examples directed principally to MIP-1alpha-targeted betacoronavirus vaccine constructs and a smaller number of anti-mouse MHCII scFv-targeted constructs. Representative examples include the MIP-1alpha/RBD constructs VB2049 and VB2060 and the anti-mouse MHCII scFv/RBD construct VB2059 (starting at ¶[0575]; Examples 2-3a and 4-11.) The specification specifically identifies CCR1, CCR3, and CCR5 as receptors for the chemokine-targeting embodiments and provided MIP-1alpha containing vaccine constructs employing this targeting approach.
The specification does not provide working examples establishing that targeting units other than the disclosed MIP-1alpha based targeting units that interact with CCR1, CCR3, or CCR5 will satisfy the claimed internalization requirement. The specification does not provide working examples directed to CD14- or CD40-targeted betacoronavirus constructs, nor does the specification provide working examples across the remaining HLA, CD14, CD40, chemokine-receptor, and Toll-like receptor scope of the other rejected claims. The disclosed examples therefore do not establish enablement across the full scope of claims 1, 10, 42, 55-56, 59-60, 64-65, and 71.
Guidance in the specification. The specification provides guidance regarding candidate APC surface molecules and identifies antibody-binding regions, natural or synthetic ligands, MIP-1alpha, and anti-HLA/MHC class II targeting approaches. The specification also states generally that binding of the targeting unit to its cognate receptor leads to internalization of the polypeptide/dimeric protein/vaccine into the APC, and more specifically describes MIP-1alspha as causing internalization through classical and cross-presentation pathways (¶[0417-0418].)
However, the specification does not provide sufficient guidance regarding how to identify targeting units across the full claimed receptor scope that will cause internalization of the claimed polypeptide into APCs. In particular, the specification does not explain why binding to any member of the recited receptor classes would be sufficient to produce the claimed internalization, or identify a general structural or functional characteristic that permits one skilled int eh art to predict which targeting units will work. The disclosure likewise does not explain how differences in the receptor-binding interaction, the particular receptor trafficking pathway, or the configuration of the complete dimeric vaccine construct affect whether the claimed internalization occurs.
Quantity of experimentation necessary. To practice the full scope of claims 1, 10, 42, 55-56, 59-60, 64-65, and 71, one skilled in the art would need to select targeting molecules directed to the different claimed receptor classes, prepare the corresponding encoded vaccine constructs, and test the resulting constructs for receptor interaction and internalization into APCs. Where a candidate failed, further targeting molecules or binding configurations would need to be prepared and evaluated to determine which members of the claimed genus possess the required property.
Such experimentation would not merely involve the routine application of known methods to embodiments reasonably expected to work. Instead, one skilled in the art would need to prepare and test additional embodiments to determine whether they satisfy the claimed function of interacting with the recited APC surface molecule in a manner capable of leading to internalization of the polypeptide into the APC. Although the individual methods used to prepare and test candidate embodiments may have been known in the art, the relevant inquiry is not whether one skilled in the art could perform the required assays. The relevant inquiry is whether the specification provides sufficient guidance to identify and practice the embodiments falling within the full scope of the claims without undue experimentation. Here, one skilled in the art would need to prepare and test additional targeting units and encoded polypeptide constructs to determine which embodiments satisfy the claimed APC-interaction and internalization function.
Amgen. The Supreme Court has explained that a specification need not describe with particularity how to make and use every embodiment within a claimed class. However, the disclosure must enable one skilled in the art to make and use the full scope of the claimed invention. A reasonable amount of experimentation may be permissible depending on the nature of the invention and the underlying art. Amgen Inc. v. Sanofi, 598 U.S. 594, 610-13 (2023).
In the instantly claimed invention, the specification describes MIP-1alpha-targeted vaccine constructs and MHC class II directed vaccine constructs, but the claims also encompass targeting units directed to the materially broader classes of HLA, CD14, CD40, chemokine receptors, and Toll-like receptors, subject to the functional requirement that the interaction be capable of leasing to internalization of the polypeptide into an APC. Claim 71 narrows the receptor genus to CCR1, CCR3, and CCR5, but still encompasses targeting units other than the particular MIP-1alpha targeting units taught by the specification. The specification does not identify a general quality or provide sufficient guidance that would allow one skilled in the art to practice that broader scope without undue experimentation.
Conclusion. For the reasons discussed above, the specification does not enable one skilled in the art to make and/or use the full scope of the invention recited in claims 1, 10, 42, 55-56, 59-60, 64-65, and 71 without undue experimentation.
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 1, 7, 9, 42, 48, 52, 55-56, and 59-60 under 35 U.S.C. 102(a)(2) as being anticipated by Cheresh et. al. (WO2021216954A1, Priority 04/23/2020; hereafter “Cheresh”) as evidenced by Bogen et. al. (US20180030155A1, Pub. 02/01/2018; hereafter “Bogen”) is withdrawn in light of the amendments to the claims.
Claim Rejections - 35 USC § 103
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 16, 46, and 63-65 under 35 U.S.C. 103 as being unpatentable over Cheresh as evidenced by Bogen as applied to claims 1, 7, 9, 42, 48, 52, 55-56, and 59-60 above, and further in view of Bogen (supra) and Malone et. al. (Malone B, et. al. bioRxiv 2020.04.21.052084; Now published in Scientific Reports.; hereafter “Malone”) is withdrawn in light of the amendments to the claims.
(Rejection withdrawn.) The rejection of Claim 67 under 35 U.S.C. 103 as being unpatentable over Cheresh, Bogen, and Malone as applied to claims 1, 7, 9, 16, 42, 46, 48, 52, 55-56, 59-60, 63-65 above, and further in view of Granum et. al. (US20190022202A1, Pub. 01/24/2019; hereafter “Granum”) is withdrawn in light of the amendments to the claims.
(Rejection withdrawn.) The rejection of Claim 10 under 35 U.S.C. 103 as being unpatentable over Cheresh, Bogen, and Malone as applied to claims 1, 7, 9, 16, 42, 46, 48, 52, 55-56, 59-60, 63-65 above, and further in view of Zion et. al. (US20210346490A1, Priority 04/10/2020; hereafter “Zion”) is withdrawn in light of the amendments to the claims.
(New rejection.) Claims 1, 10, 42, 46, 48, 55-56, 59-60, and 64-65 are rejected under 35 U.S.C. 103 as being unpatentable over Bogen et. al. (US20180030155A1, Pub. 02/01/2018; CITED ART OF RECORD; hereafter “Bogen”) and in further view of Zion et. al. (US20210346490A1, Priority 04/10/2020; Also 63/008,509 priority Doc citations; CITED ART OF RECORD: hereafter “Zion”.)
NB: As Applicant has argued that Zion fails to have proper priority to the cited elements, the paragraphs and relevant text from the priority doc 63/008/509, filed 04/10/2020, is also included.
The Prior Art
Bogen teaches recombinant antibody-based molecules that trigger both T-cell and B-cell immune responses, wherein the recombinant molecules comprise at least one targeting unit and at least one antigenic unit connected through a dimerization motif (entire document; see abstract.) Bogen teaches that these “vaccibodies” can be engineered to trigger both a T cell and B cell response (entire document; see abstract; ¶[0002]), and that in their design the antigenic unit in the vaccibody can be a viral surface protein antigen found in the viral envelope (reference claims 1, 24-26, 38, 60-62; Example 16 at ¶[0114]). Bogen teaches that Vaccibodies comprise a dimer of a monomeric unit having an APC-targeting moiety connected through a hinge region and a Cgamma3 domain to an antigenic moiety, and further teaches DNA and RNA sequences encoding the recombinant molecule and immunization using Vaccibody DNA, RNA, or protein (Fig. 1, reference claims 36-38, 72-79). Bogen teaches wherein the antigenic unit would ideally comprise the complete protein in its native conformation (¶[0007][0009]), which would inherently, under broadest reasonable interpretation, include multiple epitopes linked together by native, non-immunogenic amino acids (which can be reasonably interpreted as “linkers”), and would induce both humoral and cellular T cell responses (¶[0009]). Bogen teaches the targeting unit can target surface molecules on antigen presenting cells (APC) such as HLA, CD14, CD40, toll-like receptors (TLRs), or chemokine receptors (reference claims 51-53; ¶[0082]) or MHC class II proteins (¶[0013-0018][0040]; instant claim 42). Bogen specifically demonstrates anti-CD14 and anti-HLA-DP targeting units and teaches MIP-1α and RANTES as chemokine targeting units (Examples 7, 12, 13; Fig. 25). Bogen teaches the targeting unit may be MIP-1α (¶[0061]; reference claims 11-12, 46-47), and teaches the divalent molecule would comprise a flexible hinge region (¶[0009-0010]; instant claim 48). Bogen teaches MIP-1α as a targeting unit in the vaccibody format, and reports production of a vaccibody construct having MIP-1α as the targeting unit and teaches MIP-1α as a chemokine targeting ligand (Example 7, Fig. 25, reference claims 9-11 and 45-47; instant claim 46). Bogen teaches the vaccibody may be encoded by a nucleotide, such as DNA or RNA, and can be introduced into a cell via vectors, such as viral vectors (¶[0010][0045-0046]; instant claim 56). Bogen teaches that Vaccibodies are produced and secreted as functional dimerized molecules (¶[0083]). Bogen teaches methods of making the vaccibodies, including transfecting cells with nucleic acids encoding said vaccibodies, culturing the cells, and collecting the supernatant from said cells (¶[0015-0016][0031][0036][0043]). Said supernatant could be purified for the secreted vaccibody in sterile PBS for use in immunogenic compositions (¶[0063]). Bogen teaches pharmaceutical compositions which comprise vaccibody RNA, DNA, or proteins (¶[0010][0045]; instant claims 64-65). Bogen teaches that the Vaccibody is dimeric and that the hinge and Cγ3 domains facilitate formation of the dimer through covalent and non-covalent interactions (Fig. 1; reference claims 38 and 63-71; instant claim 60).
Bogen further teaches that the Vaccibody is targeted to surface molecules on APCs and that “the complex is taken up by receptor-mediated endocytosis” followed by processing and antigen presentation (Fig. 2). Bogen explains that bivalent binding increases the likelihood of receptor-mediated endocytosis into the APC and subsequent degradation within the APC (Fig. 2; ¶[0013][0038]). Accordingly, Bogen teaches interaction of the targeting unit with an APC surface molecule that is capable of leading to internalization of the vaccine polypeptide into APC.
While Bogen teaches the majority of instant claim 1, and Bogen teaches that the vaccibody may be bound to a viral surface antigen, Bogen fails to teach that the vaccibody would specifically be attached to a betacoronavirus Spike protein antigen, namely the RBD of said Spike protein. However,
Zion teaches fusion proteins comprising SARS CoV-2 S proteins, namely those portions which comprise the highly antigenic receptor binding domain (RBD) of said protein (entire document; see abstract.) Zion teaches the S protein linked to a fragment of an antibody (Fc fragment; entire document; see abstract.) Zion teaches SEQ ID NO: 11, which is 100% identical to instant SEQ ID NO: 231 (see alignment below, “Qy: US Provisional App 63/008,509 SEQ ID NO: 11, Db: instant SEQ ID NO: 231; instant claim 10).
Query Match 20.4%; Score 1369; DB 1; Length 253;
Best Local Similarity 100.0%;
Matches 253; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 331 NITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDL 390
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 NITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDL 60
Qy 391 CFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYN 450
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 CFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYN 120
Qy 451 YLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRV 510
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 YLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRV 180
Qy 511 VVLSFELLHAPATVCGPKKSTNLVKNKCVNFNFNGLTGTGVLTESNKKFLPFQQFGRDIA 570
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 VVLSFELLHAPATVCGPKKSTNLVKNKCVNFNFNGLTGTGVLTESNKKFLPFQQFGRDIA 240
Qy 571 DTTDAVRDPQTLE 583
|||||||||||||
Db 241 DTTDAVRDPQTLE 253
Zion teaches the proteins may be used in pharmaceutical compositions to treat disease caused by SARS CoV-2 (entire document; see abstract; reference claim 19; ‘509 see abstract; ¶[21-22].) Zion teaches that conjugation of the antigen to the Fc domain increases the plasma half-life due to its interaction with the neonatal Fc-receptor (FcRn) in addition to slower renal clearance of the Fc fusion protein due to the large molecule size, resulting in in vivo recycling of the molecule achieving prolonged activity of the linked peptide and improved solubility and stability of the Fc fusion protein molecule (¶[0007]; see ¶[8] of ‘509). Zion specifically teaches SARS-CoV-2 and vaccines for prophylactic and therapeutic immunization against SARS-CoV-2 (‘509 ¶[42]; Example starting at ¶[104]; instant claim 55).
Given the teachings of Bogen, one would be apprised as to the usefulness of vaccibodies in the targeted delivery of viral surface protein antigens to APCs. Given the teachings of Zion, one would be apprised as to highly antigenic surface S protein and RBD sequences which could be used in such a platform. Therefore, arriving at the limitations of instant claim 1 would be obvious for a skilled artisan, given the combined teachings of Bogen and Zion. Further, as Bogen teaches the recombinant polypeptide encoded by the vaccibody nucleic acid and production of such vaccibody proteins following nucleic acid expression, and since Bogen teaches the antigenic portion may be replaced with another antigen polypeptide, and with the teachings of the RBD of SARS-CoV-2 as a vaccine antigen in Zion, substitution of Zion’s RBD into the Vaccibody of Bogen would predictably produce the corresponding APC-targeting RBD-containing polypeptide of instant claim 59.
It would have been obvious to one of ordinary skill in the art to modify the methods and compositions taught by Bogen in order to utilize known SARS CoV-2 S protein antigens for the vaccibodies, thereby generating a therapeutic that could treat SARS CoV-2 infections therapeutically or prophylactically. One would have been motivated to do so, given the suggestion by Zion that the RBD of the SARS-CoV-2 spike protein was useful in an antigenic platform for vaccines against SARS-CoV-2. There would have been a reasonable expectation of success, given the knowledge that T cell epitopes were meant to be included as a part of vaccibodies, as taught by Bogen, and also given the knowledge that Bogen teaches the use of viral surface protein antigens in vaccibody constructs. There would be further reasonable expectation of success, given that known sequences for SARS CoV-2 highly immunogenic RBDs were available in the art, given the teachings of Zion, and given that Zion provided motivation to fusing the RBD to antibody regions to increase stability, targeting, and half-life of the antigen. 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.
(New rejection.) Claims 67 and 71 are rejected under 35 U.S.C. 103 as being unpatentable over Bogen and Zion as applied to claims 1, 10, 42, 46, 48, 55-56, 59-60, and 64-65 above, and further in view of Granum et. al. (US20190022202A1, Pub. 01/24/2019; hereafter “Granum”.)
The Prior Art
The teachings of Bogen and Zion have been set forth supra. While Bogen teaches about vaccibodies in detail, Bogen fails to provide sequences for the vaccibodies as instantly claimed. Zion fails to cure this deficiency. However, sequences for vaccibody frameworks were known in the art, as evidenced by the teachings of Granum.
Granum teaches vaccibodies, namely vaccine compositions which comprise a polynucleotide comprising a nucleotide sequence encoding a targeting unit, a dimerization unit, a first linker and an antigenic unit, wherein said antigenic unit comprises n−1 antigenic subunits, each subunit comprising at least a part of an epitope sequence, or the vaccine comprises a polypeptide encoded by the polynucleotide or a dimeric protein consisting of two polypeptides encoded by the polynucleotide (entire document; see abstract.) Granum teaches SEQ ID NO: 3, which is 100% identical to instant SEQ ID NO: 233 (see ABSS sequence search in file wrapper regarding 16/068,449; instant claim 67). Granum teaches targeting units for the vaccibodies, preferably wherein the targeting unit has affinity for a chemokine receptor selected from CCR1, CCR3 and CCR5. More preferably, the nucleotide sequence encoding the targeting unit according to Granum encodes the chemokine hMIP-1alpha (LD78beta), which binds to its cognate receptors, CCR1, CCR3 and CCR5 expressed on the cell surface of APCs (¶[0153]; reference claim 15; specific embodiment #36 at ¶[0257]; instant claim 71).
Given the teachings of Bogen, Zion, and Granum, one would be apprised as to the usefulness of vaccibodies in the targeted delivery of antigens to APCs. Given the teachings of Bogen in view of Zion, one of skill in the art would be apprised to the usefulness of using the vaccibody platform for delivery of SARS CoV-2 antigens. Given the teachings of Granum, one would be apprised as to at least one framework for vaccibodies for which antigens could be inserted, and specific targeting units such as CCR1, CCR3, and CCR5. Therefore, arriving at the limitations of instant claims 67 and 71 would be obvious for a skilled artisan, given the combined teachings of Bogen, Zion, and Granum.
It would have been obvious to one of ordinary skill in the art to modify the methods and compositions taught by Bogen in order to utilize known frameworks for the vaccibodies, thereby generating a therapeutic that could potentially have cross-protection against multiple SARS CoV-2 strains or other coronaviruses. One would have been motivated to do so, given the suggestion by Zion that SARS-CoV-2 Spike protein/RBD epitopes were known and used in the art as a vaccine antigen. There would have been a reasonable expectation of success, given the knowledge that T cell epitopes were meant to be included as a part of vaccibodies, as taught by Bogen and Granum, and also given the knowledge that Bogen teaches the use of viral surface protein antigens in vaccibody constructs. There would be further reasonable expectation of success, given that known sequences for vaccibody constructs were available in the art, given the teachings of Granum. 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's arguments filed 07/16/2026 have been fully considered. While the 35 USC 102 rejection over Cheresh as evidenced by Bogen has been withdrawn, and the subsequent 35 USC 103 rejections which utilized these teachings as a basis have also been withdrawn, a new obviousness rejection has been made utilizing the teachings of Bogen and Zion, and the arguments as applicable to the instant claims and their obvious nature in view of these teachings will be addressed as applicable herein.
Applicant argues that there would be no motivation to combine with Cheresh, and provides further arguments regarding the teachings of Cheresh. As Cheresh is no longer utilized in the current obviousness rejections, said arguments are moot.
Applicant argues that Zion fails to teach SEQ ID NO: 231 before the priority date of the instant claims. Zion was noted as having SEQ ID NO: 2 which aligned with instant SEQ ID NO: 231. SEQ ID NO: 11 of Zion, which has clear priority back to the provisional filing 63/008,509, filed 04/10/2020, aligns with 100% identity to instant SEQ ID NO: 231 (see alignment supra.) The ‘509 provisional expressly discloses SEQ ID NO: 11, and the relevant subject matter is the disclosed amino acid sequence, not the particular numerical identifier subsequently assigned to that sequence. Renumbering an identical sequence in a later filed document does not change the underlying disclosure present in the earlier application. Accordingly, because the sequence relied upon is expressly present in the ‘509 disclosure, Zion is entitled to the 04/10/2020 effective filing date with respect to that sequence notwithstanding the different sequence numbering which may have been used in the later application. Therefore, this line of argument is not persuasive.
Applicant further argues that the vaccination teachings in the priority document are prophetic and that Zion did not provide experimental immunogenicity data for the RBD-Fc fusion protein as of the priority date. The Examiner agrees that the relied upon vaccine examples in the priority document are prophetic. That fact, however, does not remove the disclosure from the prior art or establish that a person of ordinary skill would have lacked a reasonable expectation of success. Prophetic examples are permissible patent disclosures and may describe how an embodiment is to be made and used even though the particular experiment has not actually been performed. See MPEP §2164.02. Moreover, prior art is presumed operable where it expressly teaches the relied-upon subject matter, and proof of therapeutic efficacy is not required for a prior art disclosure to be enabling. See MPEP §2121, also In re Sasse, 629 F.2d 675, 207 USPQ 107 (CCPA 1980), Impax Labs. Inc. v. Aventis Pharm.Inc., 468 F.3d 1366, 1383, 81 USPQ2d 1001, 1013 (Fed. Cir. 2006) (citing Rasmusson v. SmithKline Beecham Corp., 413 F.3d 1318, 1326, 75 USPQ2d 1297, 1302 (Fed. Cir. 2005)). Indeed, even a non-enabling reference may be considered for what it teaches in an obviousness determination under 35 USC 103. See MPEP§2121.01.II, Beckman Instruments v.LKB Produkter AB, 892 F.2d 1547, 1551, 13 USPQ2d 1301, 1304 (Fed. Cir. 1989).
Here, Zion does substantially more than merely identify RBD-Fc as an unexplored possibility. The priority disclosure provides the particular RBD-Fc sequences, describes recombinant production of the fusion protein, identifies pharmaceutical formulations and routes of administration, and sets forth detailed vaccination and testing protocols for evaluating the resulting antibody response in animal models. The absence of completed immunogenicity data therefore does not reduce Zion’s disclosure to an unsupported invitation to experiment. Rather, Zion identifies the specific antigenic construct and provides a concrete means for making, administering, and evaluating it. Therefore, this line of argument is not persuasive.
Applicant argues that Zion provides no evidence that the RBD-Fc fusion protein would fold correctly, would be functional as a vaccine, or would induce an immune response. This argument improperly evaluates Zion in isolation and imposes a requirement of certainty rather than a reasonable expectation of success. The rejection is based on the combined teachings of Bogen and Zion (and further Granum). Bogen already teaches a nucleic acid encoding vaccine platform comprising an APC-targeting unit, a dimerization unit, and an interchangeable antigenic unit. Bogen expressly teaches that its antigenic unit may be replaced by a polypeptide derived from an antigenic source to provide a vaccine directed to other antigens, including antigens derived from infectious agents. Bogen also demonstrates expression of functional multimeric vaccine proteins following transfection and teaches that APC targeting results in receptor-mediated uptake and enhanced immune responses. Bogen therefore provides an established expression and vaccination platform into which the antigen identified by Zion would have been incorporated.
Zion supplies the particular SARS-CoV-2 RBD antigen sequence and expressly identifies an RBD-containing fusion protein for prophylactic vaccination. This targeting of RBD was not done in isolation, as Zion notes the sequence similarity between SARS-CoV-1 and SARS-CoV-2 spike proteins, and the targeting of SARS-CoV-2 spike protein mechanism to gain entry into cells through binding to ACE2 on the host cell, namely through the use of the RBD of said Spike protein. Zion further explains that the RBD-Fc protein may be recombinantly expressed in mammalian cells, describes formation of the Fc-mediated homodimer, and identifies the RBD portion as the antigen intended to induce SARS-CoV-2 antibodies. The disclosure of Zion therefore provides affirmative technical direction concerning production and use of the RBD antigen rather than merely naming an unexplored sequence.
Obviousness does not require absolute predictability or certainty that the proposed modification will succeed; the proper inquiry is whether a person of ordinary skill would have had a reasonable expectation of success (MPEP § 2143.02). Bogen teaches that antigenic sequences from infectious agents can be substituted into its vaccine platform and expressed as functional vaccine constructs, while Zion specifically identifies the SARS-CoV-2 RBD sequence as antigenic for prophylactic vaccination. These combined teachings would have provided a person of ordinary skill with a reasonable expectation that incorporation of the RBD antigen of Zion into the vaccine platform of Bogen would result in an expressed vaccine construct capable of inducing an immune response. The fact that biological systems can retain some uncertainty does not establish the absence of a reasonable expectation of success.
Applicant’s argument concerning whether the particular RBD-Fc of Zion would fold correctly also does not address the rejection as made. The rejection does not require bodily incorporation of Zion’s entire RBD-Fc construct into Bogen; Zion is relied upon for its teaching of the SARS-CoV-2 RBD antigen and sequence, while Bogen supplies the claimed APC-targeted, dimeric, polynucleotide-encoded vaccine architecture. The test for obviousness is what the combined teachings of the references would have suggested to one of ordinary skill, not whether the physical structures disclosed in the references would be combined unchanged. See MPEP §2145 and In re Keller, 642 F.2d 413, 425, 208 USPQ 871, 881 (CCPA 1981). Therefore, this line of argument is not persuasive.
Applicant’s contention that Zion teaches away from a polynucleotide vaccine is also not persuasive. Zion discusses perceived disadvantages of nucleic acid vaccine approaches and states a preference for a recombinant protein subunit approach. However, Zion does not state that nucleic acid vaccines are inoperable, incapable of producing the desired antigen, or incapable of inducing protective immunity. To the contrary, in the same discussion, Zion expressly recognizes the Pfizer/BioNTech and Moderna mRNA vaccines and notes their reported Phase III efficacy exceeding 90% (¶[0104][0116]). Zion therefore acknowledges that nucleic acid expression vaccines were capable of successfully producing a protective immune response against SARS-CoV-2. Zion’s concerns relate principally to matters such as duration of antigen expression, durability, manufacturing, and storage, rather than an inability to produce an immunogenic vaccine.
A reference does not teach away merely because it expresses a preference for one alternative or identifies disadvantages associated with another. A teaching away requires that the reference criticize, discredit, or otherwise discourage the claimed solution in a manner that would have led a person of ordinary skill away from the proposed modification. See MPEP §2145 and In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004). See also UCB, Inc. v. Actavis Labs, UT, Inc., 65 F.4th 679, 692, 2023 USPQ2d 448 (Fed. Cir. 2023). A known alternative does not become nonobvious merely because another approach is described as preferable.
Further, the rejection does not rely upon Zion for the proposition that a nucleic acid Vaccibody platform should be selected. Bogen expressly teaches that platform and demonstrates vaccination using DNA encoding the recombinant vaccine construct. Zion is relied upon for the SARS-CoV-2 RBD antigen. Zion’s preference for administration of its RBD as a recombinant protein does not negate the express teaching of Bogen that the antigenic sequences from infectious agents may be substituted into its nucleic acid encoded vaccine platform. Considered as a whole, the references therefore do not direct a skilled artisan away from the claimed combination. Therefore, this line of argument is not persuasive.
Applicant’s assertion that the claimed invention produced surprising and unexpected results has also been considered but is insufficient to overcome the prima facie case of obviousness. Evidence of unexpected results must establish that the observed result was in fact unexpected relative to what the closest prior art would have led a person of ordinary skill to expect. Merely characterizing a result as surprising, or showing that an embodiment works well, does not establish unexpectedness. See MPEP §§716.02 and 716.02(a).
Bogen already teaches that APC-targeted Vaccibody constructs enhance antigen presentation and immune responses, and Zion identifies SARS-CoV-2 RBD as an antigen intended to generate anti-SARS-CoV-2 antibodies. Accordingly, the fact that a Bogen-type APC-targeted construct containing a SARS-CoV-2 RBD elicits an immune response is an expected result of the combination rather than, standing alone, evidence of nonobviousness. Bogen experimentally reports enhanced immune responses produced by APC-targeted vaccibodies and expressly teaches substitution of antigens from infectious agents into the platform.
To the extent Applicant relies upon the magnitude, speed, durability, neutralizing activity, or Th1 character of responses obtained with particular constructs such as VB2049 or VB2060, those results are substantially narrower than the scope of instant claim 1. Instant claim 1 is not limited to a particular targeting sequence, such as MIP-1alpha, a particular RBD sequence, VB2049, VB2060, a specified dose, a specified vaccination schedule, a minimum antibody titer, a particular neutralization potency, or a specified Th1 response. The instant specification itself reports materially different responses among different constructs falling within the broader vaccine concept, including differences between MIP-1alpha-targeted and MHC-II-targeted constructs and among different RBD-containing vaccibody constructs.
Objective evidence of unexpected results must be reasonably commensurate in scope with the claims for which the evidence is offered. See MPEP§716.02(d). Results obtained for one or a small number of specifically configured Vaccibody constructs therefore do not establish that the entire genus encompassed by instant claim 1, including the different recited APC targets, targeting units, RBD portions, and other permitted construct configurations, possesses the alleged unexpected property. Additionally, any comparison relied upon to establish unexpected results must provide a meaningful comparison with the closest prior art and must establish a nexus between the asserted improvement and the feature that allegedly distinguishes the claimed invention from the prior art. Data showing that one claimed construct performs better than another claimed construct, or that a vaccine performs better than a negative control such as PBS, does not by itself establish that the claimed subject matter as a whole performs unexpectedly relative to the Bogen/Zion combination. Attorney argument alone cannot substitute for objective evidence establishing that the magnitude of the observed difference was unexpected to one of ordinary skill. See MPEP§ 2145 and MPEP §716.02(b).
Accordingly, Applicant has not established that the asserted results are unexpected over the closest prior art, attributable to the claimed distinction from the prior art, and commensurate in scope with the presently claimed invention. The evidence and arguments therefore do not outweigh the evidence supporting the conclusion of obviousness.
Applicant’s only arguments against Granum appear to be that Granum failed to cure the deficiencies of Cheresh. As Cheresh was not utilized in the instant rejection, such arguments are moot. No further arguments regarding Granum appear to have been presented.
For at least these reasons, Applicant’s arguments were unpersuasive with respect to the teachings of Bogen, Zion, and Granum, and the claims remain rejected as being obvious in light of the prior art.
Double Patenting
The text regarding nonstatutory double patenting was presented in a previous Office action.
(Rejection withdrawn.) The provisional rejection of Claims 1, 7, 9-10, 16, 42, 46, 48, 52, 55-56, 59-60, 63-65, 67, and 69 on the ground of nonstatutory double patenting as being unpatentable over claims 1, 19, 21, 26, 38, 40, 42, 44, 46, 48, 50, 54, 57, and 63 of copending Application No. 18/560,279 in view of Bogen and Zion (supra) is withdrawn in light of the amendments to the claims.
(New rejection.) Claims 1, 10, 42, 46, 48, 52, 55-56, 64-65, 67, 69, and 71 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 19, 21, 26, 38, 40, 42, 44, 46, 48, 50, 54, 57, and 63 of copending Application No. 18/560,279 in view of Bogen, Zion, and Granum (supra).
Both are drawn to vectors comprising nucleic acids encoding a targeting unit that targets antigen-presenting cells, a multimerization unit, such as a dimerization unit, and an antigenic unit comprising one or more antigens or parts thereof. Both claim the antigens may be from pathogens. Both claim the targeting unit comprises a moiety that interacts with surface molecules on the antigen-presenting cells, such as TLRs. Both claim the multimerization unit comprises a hinge region, a linker, and can promote dimerization of the resulting molecule. Both claim the vector may be within a pharmaceutically acceptable composition. Both claim the composition may be used to treat infectious disease. Both claim the vector may be introduced into a host cell for expression of the peptide.
While the instant and reference claims are both drawn to nucleic acids which may encode the vaccibody, the ‘279 claims provide that the nucleic acid is a vector that also encodes a further “immunostimulatory compound” as a separate molecule. However, such a difference would be obvious given the teaching of Bogen, which teach that the vaccibody may be delivered via a vector, specifically a viral vector, and under broadest reasonable interpretation, the viral proteins encoded by said viral vector can reasonably be interpreted as “immunostimulatory molecules”(¶[0046] of Bogen). Granum provides additional information regarding the targeting units and sequences associated with the Vaccibodies (see supra.) Additionally, the ‘279 claims are drawn generically to any pathogen and using said vector to treat infection; the inclusion of SARS CoV-2 antigens in such a construct would be an obvious modification to the system, given the combined teachings of Bogen, Zion, and Granum (detailed supra). Therefore, the differences between the instant claims and the ‘279 claims would be obvious modifications to employ for a skilled artisan given the teachings of the prior art, and the claims are not patentably distinct.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant's arguments filed 07/16/2026 have been fully considered but they are not entirely persuasive. While the original rejection over the ‘279 claims has been withdrawn, a new rejection is set forth supra.
Applicant has requested that the non-statutory obviousness-type double patenting rejection be held in abeyance until allowable subject matter is indicated in the present application. However, said rejection must be maintained as a matter of record until the appropriate terminal disclaimers have been filed, or until the claims have been amended in such a way as to not claim patently identical subject matter.
(New rejection.) Claims 1, 10, 42, 46, 48, 52, 55-56, 64-65, 67, and 71 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9, 11, 20-21, 32-35 of copending Application No. 18/588,492 in view of Bogen, Zion, and Granum (supra).
Both are drawn to vectors comprising nucleic acids encoding a targeting unit that targets antigen-presenting cells, a multimerization unit, such as a dimerization unit, and an antigenic unit comprising one or more antigens or parts thereof. Both claim the antigens may be from pathogens. Both claim the targeting unit comprises a moiety that interacts with surface molecules on the antigen-presenting cells, such as TLRs. Both claim the multimerization unit comprises a hinge region, a linker, and can promote dimerization of the resulting molecule. Both claim the vector may be within a pharmaceutically acceptable composition. Both claim the composition may be used to treat infectious disease. Both claim the vector may be introduced into a host cell for expression of the peptide.
While the instant and reference claims are both drawn to nucleic acids which may encode the vaccibody, the ‘492 claims only generically recite that the antigenic unit may be from a virus. The inclusion of SARS CoV-2 antigens in such a construct would be an obvious modification to the system, given the combined teachings of Bogen, Zion, and Granum (detailed supra in the 103 rejections). Therefore, the differences between the instant claims and the ‘492 claims would be obvious modifications to employ for a skilled artisan given the teachings of the prior art, and the claims are not patentably distinct.
This is a provisional nonstatutory double patenting rejection.
(New rejection.) Claims 1, 10, 42, 46, 48, 52, 55-56, 64-65, 67, and 71 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 22-26, 34, 43, 49, 55, and 57 of copending Application No. 18/706,648 in view of Bogen, Zion, and Granum (supra).
The ‘648 claims recite a SARS-CoV-2 immunogenic construct comprising a polynucleotide encoding an APC-targeting unit; targeting of HLA, CD14, CD40, chemokine receptors including CCR1, CCR3, and CCR5, and Toll-like receptors; human MIP-1alpha targeting; hinge- and immunoglobulin-based dimerization units; polynucleotide, polypeptide, and dimeric protein embodiments; and pharmaceutical vaccine compositions comprising a pharmaceutically acceptable carrier for prophylactic or therapeutic treatment of SARS-CoV-2 infection. Bogen further teaches that interaction of an APC-targeting Vaccibody with its target results in receptor mediated internalization, while Zion teaches the SARS-CoV-2 RBD antigen relied upon in the instant claims, including a sequence corresponding to SEQ ID NO: 231. Although the instant claims and the ‘684 claims are not identical, they are not patentably distinct because the substitution of Zion’s known SARS-CoV-2 RBD antigen for the SARS-CoV-2 antigenic material recited in the reference claims, while retaining the claimed APC-targeting and dimerization platform, would have been an obvious variation, particularly in view of Bogen’s teaching of APC-targeted internalization. The additional limitations directed to the recited APC receptors, MIP-1alpha, hinge-containing dimerization units, polynucleotide and encoded polypeptide forms, dimeric proteins, vaccine preparation, and administration for prevention or treatment of SARS-CoV-2 infection likewise represent subject matter expressly claimed in ‘648 or obvious variants thereof, especially in light of the teachings of Bogen, Zion, and Granum.
This is a provisional nonstatutory double patenting rejection.
(New rejection.) Claims 1, 10, 42, 46, 48, 52, 55-56, 64-65, 67, and 71 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-28 of U.S. Patent No. 8,932,603 in view of Bogen, Zion, and Granum (supra). The patented claims recite the same underlying APC-targeted vaccine platform comprising a targeting unit, dimerization unit, antigenic unit, nucleic acid encoding embodiments, and vaccine compositions, including targeting through the APC-associated receptor classes recited in the instant claims. Bogen, Zion, and Granum establish that use of the claimed APC-targeting/internalization features, SARS-CoV-2 RBD antigen, and specifically-recited chemokine receptors would have been obvious variations of the patented subject matter, for the reasons discussed in detail supra with respect to the prior art rejections. Accordingly, the instant claims do not define a patentably distinct invention from the ‘603 claims.
(New rejection.) Claims 1, 10, 42, 46, 48, 52, 55-56, 64-65, 67, and 71 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-29 of U.S. Patent No. 9,169,322 in view of Bogen, Zion, and Granum (supra). The patented claims are directed to administration of a nucleic acid encoding the APC-targeted, dimeric, Vaccibody platform and include embodiments employing HLA, CD14, CD40, TLR, and chemokine directed targeting and viral antigens. Selection of the SARS-CoV-2 RBD antigen and the presently claimed APC targeting/internalization and chemokine receptor limitations would have been obvious modifications in view of Bogen, Zion, and Granum, as discussed in detail supra. The instant claims therefore are not patentably distinct from the ‘322 claims.
(New rejection.) Claims 1, 10, 42, 46, 48, 55-56, 59-60, 64-65, 67, and 71 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 9,796,787 in view of Bogen, Zion, and Granum (supra). The patented claims encompass the recombinant APC-targeted dimeric Vaccibody protein and related vaccine embodiments, including antibody and chemokine-based APC targeting and viral antigenic units. The use of SARS-CoV-2 RBD as the antigenic unit, expression from a polynucleotide, and the presently recited receptor and internalization limitations would have been obvious variations in view of Bogen, Zion, and Granum, whose teachings are discussed in detail supra. Accordingly, the instant claims are not patentably distinct from the ‘787 claims.
Allowable Subject Matter
(Objection withdrawn.) The objection of Claims 68 and 70 is withdrawn in light of the amendments to the claims.
Conclusion
No claims are allowed.
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.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
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.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/RACHEL B GILL/
Primary Examiner, Art Unit 1671
Prosecution Insights