DETAILED ACTION
Election/Restrictions
Applicant’s election of selected species, filed May 12, 2026, is acknowledged and entered. Claims 4 and 21 are directed to non-elected species and are withdrawn from consideration.
Claims Summary
Claim 1 is directed to an immunogenic construct comprising a polynucleotide (RNA or DNA (claim 7) comprising a nucleotide sequence encoding a polypeptide, wherein the polypeptide comprises:
A targeting unit (TU) targeting or capable of targeting APC, comprising a moiety that interacts with CCR1 and CCR5 (claim 2), such as human CCL3 (also known as MIP-1α);
A dimerization unit (DimU) comprising a hinge region and an immunoglobulin domain (claim 5); and
An antigenic unit comprising a subunit comprising one or more T-cell epitopes from a pathogen, and one or more antigens or parts or fragments thereof from a pathogen (e.g., virus (claim 33); if there is more than one T-cell epitope, they are separated from each other by T-cell epitope linkers (TL); the subunit is connected to the dimerization domain by a unit linker (UL) which is a non-immunogenic linker and/or flexible or rigid linker (claim 6), and separated from the one or more antigens by an antigen linker (AL)
Figure 1a represents an example schematic of the structure of the polypeptide:
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Claim 32 is directed to a vector comprising the construct. The polynucleotide further comprises a nucleotide sequence encoding a signal peptide (claim 8). The construct of claim 9 comprises a DNA polynucleotide comprising a sequence encoding a polypeptide comprising:
A human MIP-1α signal peptide
A human MIP-1α targeting unit
A dimerization unit which comprises:
A hinge exon h1
A hinge exon h4
A dimerization unit linker
A CH3 domain of human IgG3
A unit linker, and
An antigenic unit
Figure 2 represents an example dimeric construct wherein the antigenic unit comprises T-cell epitopes and an RBD antigen:
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Also claimed is a vaccine comprising the construct and a pharmaceutically acceptable carrier (claim 11), in a liquid formulation for injection (claim 20). The vaccine is prepared by a method comprising preparing the polynucleotide, optionally cloning it into an expression vector, and mixing the polynucleotide or the expression vector with a pharmaceutically acceptable carrier (claim 34).
Claim 22 is directed to a method of treating a subject suffering from a disease caused by a pathogen, or being in need of prevention thereof, comprising administering the vaccine. The pathogen is selected from the group consisting of virus, bacterium, fungus and parasite (claim 35).
Specification
The disclosure is objected to because it contains multiple instances of embedded hyperlinks and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1, 2, 5-9, 11, 20, 22 and 32-35 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.
Regarding claims 1, 2 and 5-7, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). Claims 8, 9, 11, 20, 22 and 32-35 are included in this rejection because they depend, directly or indirectly, from claim 1.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-3, 5-9, 11, 20, 22 and 32-35 are rejected under 35 U.S.C. 103 as being unpatentable over Granum et al. (US 2019,0022202 A1, published January 24, 2019, “Granum”) in view of Ruffini et al. (WO 2011/161244 A1, “Ruffini”). The claims are summarized above correlated with the teachings of the prior art in bold font below.
Granum discloses a DNA vaccine comprising a targeting unit, a dimerization unit, a first linker (e.g., GLGGL, non-immunogenic), and an antigenic unit (see paragraphs [0012], [0029] and [0171]) (claim 1, aspects of targeting unit, dimerization unit, unit linker and antigenic unit, and claims 6 and 7). The vaccine is a plasmid vector (see paragraph [0403] (claim 32).
The targeting unit comprises human MIP-1α, which binds to CCR1, CCR3 and CCR5 on APCs (see paragraphs [0150] and [0153]) (claims 1-3). The targeting unit comprises the signal peptide of human MIP-1α (LD78β) and the targeting unit of human MIP-1α (see paragraph [0337]) (claims 8 and 9).
The dimerization unit connects the targeting unit and the antigenic unit, and comprises a hinge region and an immunoglobulin domain (see paragraph [0337]) (claim 5). Specifically, the dimerization unit comprises hinge exons h1 and h4 connected by a non-immunogenic G-S linker to a CH3 domain of IgG3 (see paragraph [0337]) (claim 9).
The antigenic unit comprises subunits that comprise a neoepitope sequence and a second linker, and there may be more than one subunit, meaning multiple epitopes (e.g., 10-20) and epitope linkers that are non-immunogenic and flexible (see paragraphs [0120] and [0130]) (claims 1 and 6).
The vaccine further comprises a pharmaceutically acceptable carrier, including saline, water, glycerol, etc., all of which are liquid and suitable for injection (see paragraphs [0240] and [0242]) (claims 11 and 20). Granum discloses a method of preparing a polynucleotide, mixing it with a pharmaceutically acceptable carrier (see paragraph [0029]) (claim 34). Treatment of cancer is disclosed (see paragraph [0246]).
Granum does not suggest the use of T-cell epitopes from pathogens.
Ruffini discloses vaccibodies, DNA/RNA sequences encoding vaccibodies and expression vectors, comprising a targeting unit (e.g., human CCL3 isoforms), a dimerization unit (h1+h4 exons and CH3 from IgG3), and an antigenic unit (see abstract and page 9, lines 27-29). The antigenic unit comprises two identical antigens from a bacterium, or a virus (see pages 8-9, bridging paragraph, and page 16, line 25 through page 17, line 8). The epitopes are recognized by surface receptors on T-cells, which means that the epitopes are T-cell epitopes (see page 15, last paragraph) (claim 1, aspect of T-cell epitopes). Ruffini discloses treatment of infectious diseases with the constructs (see page 19, lines 11-14) using liquid formulations for injection (see pages 9-10, bridging paragraph).
It would have been obvious to have modified Granum’s construct to have T-cell epitopes from bacteria or viruses. One would have been motivated to render Granum’s construct useful for inducing immune responses to bacteria or viruses, with a reasonable expectation of success, thus addressing treatment or prevention of disease caused by pathogens, as is done in Ruffini with a similar construct (claims 1, 22, 33 and 35).
It is noted that the claims require an antigenic unit having both a T-cell epitope(s) and an antigen(s). Granum’s antigenic component comprises multiple epitopes separated by linkers, but does not explicitly disclose a distinct entity of an antigen(s). However, because T-cell epitopes are reasonably considered antigens, Granum’s antigenic component that comprises multiple epitopes reads on the instantly claimed embodiment wherein the antigenic unit comprises T-cell epitopes and antigens. Taken together with Ruffini’s teachings, the antigenic component comprises T-cell epitopes and antigens from bacteria or virus (claim 1, part c).
Therefore, the claimed invention would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-3, 7, 11, 22 and 32-35 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 10, 42, 46, 48, 55, 56, 64, 65 and 67-71 of copending Application No. 17/997,407 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other. The copending claims are directed to a vaccine comprising a pharmaceutically acceptable carrier and a polynucleotide comprising a targeting unit, such as human MIP-1α that interacts with surface receptors CCR1, CCR3 and CCR5 on APCs, a dimerization unit comprising a hinge region and linker, and an antigenic unit comprising at least one betacoronavirus epitope comprising the RBD of the spike protein. The copending claims are a species of the instantly claimed genus. A species anticipates a genus. Further, since the antigenic unit of the copending claims comprises at least one RBD epitope, the presence of two or more reads on the instantly claimed embodiment wherein there is an epitope and an antigen (i.e., an epitope is an antigen).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 5, 6, 8, 9 and 20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 10, 42, 46, 48, 55, 56, 64, 65 and 67-71 of copending Application No. 17/997,407 (reference application) as applied to claims 1-3, 7 and 11 above, and further in view of Granum et al. (US 2019,0022202 A1, published January 24, 2019, “Granum”).
Instant claim 5 is directed to embodiments wherein the dimerization unit comprises a hinge region and an immunoglobulin domain. Instant claim 6 is directed to an embodiment wherein the unit linker that connects the dimerization unit to the antigenic unit is non-immunogenic and/or flexible or rigid. Instant claim 8 is directed to an embodiment wherein the polynucleotide comprises a signal peptide. Instant claim 9 is directed to an embodiment wherein the polynucleotide encodes a polypeptide comprising a human MIP-1α signal peptide, a human MIP-1α targeting unit, a dimerization unit which comprises a hinge exon h1 and h4, a dimerization unit linker, a domain of human IgG3, a unit linker, and an antigenic unit. Instant claim 20 is directed to an embodiment wherein the vaccine is a liquid formulation for injection.
The copending claims are summarized above but do not recite the limitations of instant claims 5, 6, 8, 9, and 20. However, it would have been obvious to have claimed these embodiments that further define the invention, with a reasonable expectation of success. Granum discloses a DNA vaccine comprising a targeting unit, a dimerization unit, a first linker (e.g., GLGGL, non-immunogenic), and an antigenic unit (see paragraphs [0012], [0029] and [0171]) (addressing instant claim 6). The targeting unit comprises the signal peptide of human MIP-1α (LD78β) and the targeting unit of human MIP-1α (see paragraph [0337]) (addressing instant claims 8 and 9). The dimerization unit connects the targeting unit and the antigenic unit, and comprises a hinge region and an immunoglobulin domain (see paragraph [0337]) (addressing instant claim 5). Specifically, the dimerization unit comprises hinge exons h1 and h4 connected by a non-immunogenic G-S linker to a CH3 domain of IgG3 (see paragraph [0337]) (addressing instant claim 9). Granum discloses that the vaccine further comprises a pharmaceutically acceptable carrier, including saline, water, glycerol, etc., all of which are liquid and suitable for injection (see paragraphs [0240] and [0242]) (addressing instant claim 20).
This is a provisional nonstatutory double patenting rejection.
Claims 1-3, 5-9, 11, 20, 22 and 32-35 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 5, 11, 14, 16, 19, 20, 22-26, 34, 43, 49, 55 and 57-59 of copending Application No. 18/706,648 in view of Granum et al. (US 2019,0022202 A1, published January 24, 2019, “Granum”).
Copending claim 3 is directed to an immunogenic construct comprising a polynucleotide comprising nucleotide sequence encoding a targeting unit that targets APCs, a multimerization unit (specifically, dimerization unit, copending claim 26), and an antigenic unit, wherein the antigenic unit comprises at least 77 SARS-CoV-2 T-cell epitopes. T-cell epitopes are separated by linkers (copending claim 19). The targeting unit is human MIP-1α (copending claim 25) which targets at least CCR1 and CCR5 (copending claim 23). The polynucleotide comprises a signal peptide (copending claim 34). The polynucleotide is in a vector (copending claim 43). Copending claim 55 is directed to a vaccine comprising the polynucleotide an a pharmaceutically acceptable carrier, and copending claim 57 is directed to a method for treating a disease caused by SARS-CoV-2.
Although the copending claims do not make a distinction between T-cell epitopes and antigens in the antigenic unit of the construct, T-cell epitopes are reasonably considered antigens. Thus, the copending construct reads on the instantly claimed construct.
The copending embodiments do not recite all of the details of the instant claims, such as a unit linker between the dimerization domain and the antigenic subunits, a dimerization domain comprising a hinge region and an immunoglobulin domain, a non-immunogenic linker and flexible or rigid, DNA, a human MIP-1α signal peptide, a dimerization unit which comprises a hinge exon h1 and h4, a dimerization unit linker, a domain of human IgG3, and a liquid formulation for injection.
However, it would have been obvious to have claimed these embodiments that further define the invention, with a reasonable expectation of success. Granum discloses a DNA vaccine comprising a targeting unit, a dimerization unit, a first linker (e.g., GLGGL, non-immunogenic), and an antigenic unit (see paragraphs [0012], [0029] and [0171]) (addressing instant claims 6 and 7). The targeting unit comprises the signal peptide of human MIP-1α (LD78β) and the targeting unit of human MIP-1α (see paragraph [0337]) (addressing instant claim 9). The dimerization unit connects the targeting unit and the antigenic unit, and comprises a hinge region and an immunoglobulin domain (see paragraph [0337]) (addressing instant claim 5). Specifically, the dimerization unit comprises hinge exons h1 and h4 connected by a non-immunogenic G-S linker to a CH3 domain of IgG3 (see paragraph [0337]) (addressing instant claim 9). Granum discloses that the vaccine further comprises a pharmaceutically acceptable carrier, including saline, water, glycerol, etc., all of which are liquid and suitable for injection (see paragraphs [0240] and [0242]) (addressing instant claim 20).
Although the copending claims do not make a distinction between T-cell epitopes and antigens in the antigenic unit of the construct, T-cell epitopes are reasonably considered antigens. Thus, the copending construct reads on the instantly claimed construct.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claim is allowed.
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Any inquiry concerning this communication or earlier communications from the examiner should be directed to Stacy B. Chen whose telephone number is 571-272-0896. The examiner can normally be reached on M-F (7:00-4:30). If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Thomas Visone, can be reached on 571-270-0684. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
/STACY B CHEN/Primary Examiner, Art Unit 1672
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