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 .
Election/Restrictions
Applicant’s election without traverse of Group I, species of antigenic unit which is one or more T-cell epitopes of a self-antigen in the reply filed on 06/06/2026 is acknowledged.
Upon further consideration, the requirement for species selection of targeting moiety is withdrawn.
Claims 64 in part and dependent claims in part are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention of a polypeptide or multimeric protein of the polypeptide, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 06/06/2026.
Information Disclosure Statement
The information disclosure statement filed 02/08/2026 fails to comply with 37 CFR 198(b)(1)-(5), which requires the following: (1) Each U.S. patent listed in an information disclosure statement must be identified by inventor, patent number, and issue date; (2) Each U.S. patent application publication listed in an information disclosure statement shall be identified by applicant, patent application publication number, and publication date; (3) Each U.S. application listed in an information disclosure statement must be identified by the inventor, application number, and filing date; (4) Each foreign patent or published foreign patent application listed in an information disclosure statement must be identified by the country or patent office which issued the patent or published the application, an appropriate document number, and the publication date indicated on the patent or published application; (5) Each publication listed in an information disclosure statement must be identified by publisher, author (if any), title, relevant pages of the publication, date, and place of publication. The information disclosure statement has been placed in the application file, but the information referred to therein that does not comply with 37 CFR 1.98(b) has not been considered.
The IDS filed 02/08/2024 was considered but several citations were lined- through. In some cases, the information in the citation(s) were incomplete or cut off (e.g., FOR #54, NPL #55). Reference 64 has insufficient information because it does not list what it is, for example, if it is a thesis or from a journal.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the specification are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Assuming the sequence “GWYRSPFSVVH” on p. 96, lines 22 and 32, is present in the Sequence Listing:
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Specification
All references in this Office action to the location in the specification are to the location in the clean substitute specification filed 03/07/2025.
The disclosure is objected to because of the following informalities: On p. 1, lines 19-20, the sequence listing name needs hyphens as used in the name of the document filed on 03/07/2026, “P5967US00-Substitute-Sequence-listing.txt”. On p. 7, line 14, the first occurrence of an abbreviation should be accompanied by its full name, so that MOG should be accompanied by “myelin oligodendrocyte glycoprotein” (see p. 25, line 24). On p. 13, line 19, there are two periods after “response”.
Appropriate correction is required.
Claim Objections
Claim 66 is objected to for reciting "MHCII" twice as part of the Markush grouping.
Claim Rejections - 35 USC § 112(b)
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.
Claim 64 and dependent claims 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 64 is indefinite because the last paragraph recites both “T cell epitopes” and “antigen-presenting cell”, and then recites “without activating the cell.” It is unclear which cell is not activated. It appears from the specification that lack of activation of the antigen-presenting cell (APC, e.g., dendritic cell) may have been intended (e.g., p. 3, lines 5-9). 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). Therefore, clarity is required.
Claim Rejections - 35 USC § 112(a)
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.
Claims 64-74 and 77-78 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.
The claims are broadly drawn to a "tolerance-inducing" construct comprising: a)
a polynucleotide comprising a nucleotide sequence encoding a targeting unit, which targets antigen-presenting cells (APCs), b) a multimerizing unit and c) an antigen unit comprising, as elected, one or more T cell epitopes of a self-antigen.
The specification teaches (p. 13, lines 9-13) that a "tolerance-inducing construct" is one that does not elicit an inflammatory immune response but rather induces tolerance towards the T cell epitopes comprised in the antigenic unit when administered to a subject in a form suitable for administration and in an amount effective to induce tolerance. The constructs generally have the structures set forth in Figures 1A-1B where a targeting unit targets antigen-presenting cells (APCs). The term "targeting unit" is referred to (p. 16, lines 11-19) as a unit that delivers the construct of the disclosure to an antigen-presenting cell and interacts with surface molecules on the APC, e.g., binds to surface receptors on the APC, without inducing maturation of the cell. The APC internalizes the construct and presents the T cell epitopes comprised in the antigenic unit on MHC on its surface in an anti-inflammatory, tolerogenic manner. In some embodiments, the targeting unit comprises or consists of a moiety that binds to a surface molecule on APC which can include such diverse proteins as TGFß receptors, interleukin receptors, GM-CSFR, FLT3, CCR7, CD11b, CD11c, CD103, CD14, CD36, CD205, CD109, VISTA, MARCO, MHCII, CD83, SIGLEC, MGL/Clec10A, ASGR (ASGR1/ASGR2), CD80, CD86, Clec9A, Clec12A, Clec12B, DCIR2, Langerin, MR, DC-Sign, Trem14, Dectin-1, PDL1, PDL2 and HVEM. Further, these targeting constructs (p. 16, lines 1-2) can be the natural ligand to the receptors, a synthetic ligand, or an scFV or an antibody or binding fragments thereof. Thus, the claims are drawn to a very broad genus of antigens or ligands that can target a genus of receptors or protein molecules on all antigen-presenting cells. Nevertheless, the construct must not only bind the target antigen, but also be internalized (see below).
Further, regarding the "antigenic" unit, the specification teaches (p. 24, lines 1-3) that the antigenic unit of the tolerance-inducing construct of the disclosure comprises one or more T cell epitopes of a self-antigen, an allergen, an alloantigen or a xenoantigen. The "number" of T cell epitopes in the antigenic unit may vary (p. 26, e.g., lines 24-30). Thus, the "antigenic" unit is drawn to a massive genus of extremely diverse amino acid sequences regarded as "epitopes" derived from any and all allergens, alloantigens, xenoantigens, self-antigens.
What the inventors have demonstrated possession of are several species of amino acid constructs that appear to have some properties of inducing Foxp3+ CD4+ T cells and inducing IL-10 while not inducing IFNγ.production. For example, when mice were vaccinated with these constructs, splenocytes were harvested and IL-10 was detected with only low background levels of IFN-γ detected (Figs. 11A-B). In another example, some constructs showed the detection of Foxp3+ cells, indicating the presence of regulatory T cells or Tregs (Figure 12). The various species of constructs are described Tables 1-3 and in many cases peptides derived from myelin oligodendrocyte glycoprotein (MOG, Table 1) have been incorporated as one species of antigenic unit into the construct, although, there are examples of constructs with GAD65 (a major autoantigen in diabetes, Table 2) and met e 1 (a shrimp allergen, Table 3). Several targeting moieties are disclosed, including human CCL3L1, murine IL-1 and, murine CD205, as well as anti-DEC205 scFVs (see first table of p. 82). The prior art discloses use of MHCII as an APC target (e.g., Lunde et al., J. Immunol. 168:2154-2162, 2002, cited in the IDS filed 2/8/2024, e.g., p. 2154, col. 2, third paragraph). The binding of the target has to be able to induce internalization of the construct, which other APC antigens have not been shown to do. The claims broadly encompass a huge genus of structurally diverse complexes as set forth above while only a few representative species have been adequately described. A description of a genus may be achieved by means of a recitation of a representative number of species, defined by structure, falling within the scope of the genus or a structure-function correlation supporting the genus. The Written Description Guidelines for Examination of Patent Applications (MPEP § 2163) indicates, "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…, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical characteristics and/or other 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 applicant was in possession of the claimed genus…." [See MPEP § 2163(II)(A)(3)(a)(ii)] The recitation of "tolerance-inducing construct" does not convey a common structure or function and is not so defined in the specification. The only multimerizing units shown to function in the construct are those of IgG3 hinge regions 1 and 4 with a glycine-serine linker to IgG3 CH3 and a glycine-leucine inker between the targeting unit and antigenic unit (Tables 1-3). Further, all disclosed functional constructs have a signal peptide as set forth in Tables 1-3. It is only in this context of constructs set forth in the Tables that they have been shown to have the recited function.
The instant specification fails to provide sufficient descriptive information, such as definitive structural or functional features of the claimed genus. The species described do not represent the genus of any and all APC targeting domains, and any and all multimerizing units, or the construct without a signal domain commensurate in scope with those disclosed. The disclosure fails to describe the common attributes or characteristics that identify members of the genus that induce tolerance and do not activate APC cells (however, see 112(b) above related to the activated cell). The fundamental factual inquiry is whether the specification conveys with reasonable clarity to those skilled in the art that, as of the effective filing date sought, inventor was in possession of the invention as now claimed. Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111 (Fed. Cir. 1991), clearly states that “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description' inquiry, whatever is now claimed.” (See page 1117.) In the instant case as the claims encompass a broad genus, the specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116). It must be shown that the inventor was in possession of the claimed invention by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention. Lockwood V. Am. Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997). As discussed above, the skilled artisan cannot envision the detailed structure of the encompassed genus of tolerance-inducing constructs, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers V. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. V. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. 26. Thus, one of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of "tolerance-inducing" constructs to describe the genus as broadly claimed.
Claim 78 is 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 a method of improving tolerance to a self-antigen, an allergen , an alloantigen or a xenoantigen in a subject by administering an effective amount of the tolerance-inducing construct according to claim 64 to a subject in need thereof, does not reasonably provide enablement for wherein the construct is not administered in an effective amount. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
Claim 78 is drawn to a method for improving tolerance to a self-antigen, an allergen, an alloantigen or a xenoantigen in a subject by administering the tolerance-inducing construct according to claim 64 to a subject. There is no requirement that the administration be in an amount effective to induce said tolerance. Regarding the treatment of undesired immune reactions, Bluestone ("Mechanisms of tolerance"; Immunol. Rev. 241(1):5-19, April 2011, p. 5, middle) teaches, “[T]he challenges in attaining and maintaining this state are underlined by the prevalence of autoimmune disease, the as-of-yet absence of routine tolerogenic therapies in organ transplantation, and the necessity to strike a balance between protecting the individual from autoimmunity while preserving responses against cancerous cell and foreign antigens.” Further, it is taught (page 14, 1st column) that current immunosuppressive treatments are usually efficient at preventing acute rejection of solid allografts. However, little progress has been made over the last two decades in avoiding chronic rejection, and current therapies induce general immunosuppression that can affect the ability of recipients to fight tumors and infections. Additionally, regarding regulatory T cells, Bluestone teaches that the notion that immune responses could be controlled by specialized suppressor T cells was only revived within the past 15 years (page 8, 1st column). These studies led to the identification of CD4+ CD25+ Foxp3+ Tregs and their crucial role in peripheral tolerance. However, the mere detection of T-regs in vitro does not predictably translate into treating in vivo autoimmune disorders or predicting that a construct may be labeled as "tolerant inducing". Even if the construct is capable of inducing tolerance, it cannot do so in vivo if it is not administered in an effective amount to do so.
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 64-74 and 77-78 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 6-8, 10-16, 17, 18, 20, 22-24, 26-50 of copending Application No. 18/560,033 (‘033, reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because
Both applications claim a tolerance-inducing construct comprising a polynucleotide comprising a nucleotide sequence encoding a polypeptide comprising a first targeting unit, an antigenic unit, which comprises one or more T cell epitopes of a self-antigen, an allergen, an alloantigen or a xenoantigen, and which construct may be a multimeric protein, such as a dimeric protein (instant claim 64 and claim 1 of ‘033). The targeting unit(s) interacts with a surface molecule(s) on an antigen-presenting cell (instant claim 1 and claim 30 of ‘033). The target may be selected from the list set forth in instant claim 66 and 68, which are respectively the same as the list in claims 31 and 33 of ‘033. The targeting unit may be an antibody, natural ligand or synthetic ligand (instant claim 67 and claim 32 of ‘033). The antigen may be the same or different (instant claims 69-70 and claims 34-35 of ‘033). The dimerizing unit may be a hinge, linker and CH3 domain of human IgG3 (instant claim 72 and claims 2-4 and 6-7, 10-11, 14-15. 17-18, 20, 22-24, 26 of ‘033). Claims 31 and 47 of ‘033 is drawn to a method of preparing a pharmaceutical composition of the polynucleotide, which renders the pharmaceutical composition itself obvious (see claims ’41-44 of ‘033 and instant claim 77 for pharmaceutical composition). Instant claim 78 is drawn to a method of improving tolerance by administering the tolerance-inducing construct, which is obvious in view of the methods of claims 49-50 of ‘033 drawn to a method of treating conditions involving undesired immune reactions by administering the polynucleotide which is the tolerance-inducing construct.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 64-74 and 77-78 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 52, 53, 57-71 of copending Application No. 18/560,868 (‘868, reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because
Both applications claim a tolerance-inducing construct comprising a polynucleotide comprising a nucleotide sequence encoding a polypeptide comprising a first targeting unit, an antigenic unit, which comprises one or more T cell epitopes of a self-antigen, an allergen, an alloantigen or a xenoantigen (instant claim 64 and claims 52-53 of ‘868). The polynucleotide in the form of a vector or ‘868 also allows for coexpression of one or more immunoinhibitory compounds as separate molecules, which reinforces the tolerance-inducing property of the encoded polypeptide (see claims 53-56 of ‘868). Both applications specify what the self-antigen may be, as well as the allergen (instant claims 70-71 and claims 57-58 of ‘868). The antigenic unit are further similarly set forth in instant claim 69 and claims 59-60 of ‘868. The target may be selected from the list set forth in instant claim 66 and 68, which are respectively the same as the list in claims 61 and 62 of ‘868. It would have been obvious wherein the targeting unit was an antibody, natural ligand or synthetic ligand because all were known and used in the prior art (instant claim 67). The targeting unit(s) interacts with a surface molecule(s) on an antigen-presenting cell (instant claim 1 and claim 61 of ‘868). The antigen may be the same or different (instant claims 69-70) and dimerizing unit may be a hinge, linker and CH3 domain of human IgG3 (instant claim 72 and claims 64-66 of ‘868). Claim 68 of ‘868 is drawn to a method of producing a vector. Both applications claim a pharmaceutical composition comprising the polynucleotide (see claim 70 of ‘868 and instant claim 77). Instant claim 78 is drawn to a method of improving tolerance by administering the tolerance-inducing construct, which is obvious in view of the method of claim 71 of ‘868 drawn to a method of treating a subject having an immune disease which is an autoimmune disease, allergic disease or graft rejection by administering the polynucleotide, which necessarily induces tolerance.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
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.
Claim(s) 64-67, 69, 70, 72-74 and 77 is/are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Lunde et al. (J. Immunol. 168:2154-2162, 2002, cited in the IDS filed 2/8/2024).
Lunde et al. teaches a construct comprising a polynucleotide comprising a nucleotide sequence encoding a targeting unit which targets antigen-presenting cells (APCs) in the form of an antibody Fab variable region comprising a binding site for an APC cell surface protein, MHC II receptor, and an antigenic unit which is a T cell epitope of an allergen and/or xenoantigen, e.g., Table 1: OVA (ovalbumin) or HEL (hen egg lysozyme), such that “When the tAb are internalized and degraded by the APC, the T cell epitopes can be loaded onto MHC molecules and presented to T cells.” (p. 2154, col. 2, second paragraph). The construct was in a vector and expressed in NSO host cells (p. 2155, col. 2, second paragraph). This construct encodes a “Troybody” (e.g., Abstract). Because it has the structure of an antibody, it inherently has a multimerizing unit which is the dimerizing human IgG3 Fc region (p. 2155, col. 1, third paragraph). It is stated (p. 2154, col. 2, third paragraph), “Troybodies have the advantage that all different professional APC expressing MHC class II molecules may be targeted.” It does not appear APCs were activated by the Troybodies; although, T cells were (p. 2156, col. 2, third paragraph and p. 2160, col. 2, second paragraph). The Troybodies were injected into mice and were, therefore, necessarily in a pharmaceutical composition with an acceptable carrier.
Alternatively, it would have been obvious wherein the APC cell is not activated as follows from the discussion on p. 2161, col. 2, third paragraph, saying, “However, Troybodies could also be used for induction of specific T cell tolerance to prevent or ameliorate autoimmune diseases. For example, Troybodies directed to APC in the thymus could induce central T cell tolerance to defined peptides. Similarly, Troybodies directed to appropriate APC, such as certain immature DC (52), could induce T cell anergy or regulatory, suppressive T cells.” Also, it would have been obvious to have the Fc domain of the Troybody be that of a human IgG3 and a linker since the T cell epitope was introduced in the human IgG3 CH1 domain (p. 2155, col. 1, third paragraph).
Claim Rejections - 35 USC § 103
Claim(s) 64-67, 69, 70-74, 77 and 78 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lunde et al. (J. Immunol. 168:2154-2162, 2002, cited in the IDS filed 2/8/2024) as applied to claims 64-67, 69, 70, 72-74 and 77 above, and further in view of Warren et al. (J. Neurol. Sci. 152: 31-38, 1997)
Lunde et al. teaches a construct comprising a polynucleotide comprising a nucleotide sequence encoding a targeting unit which targets antigen-presenting cells (APCs) in the form of an antibody Fab variable region comprising a binding site for an APC cell surface protein, MHC II receptor, and an antigenic unit which is a T cell epitope of an allergen and/or xenoantigen, e.g., Table 1: OVA (ovalbumin) or HEL (hen egg lysozyme), such that “When the tAb are internalized and degraded by the APC, the T cell epitopes can be loaded onto MHC molecules and presented to T cells.” (p. 2154, col. 2, second paragraph). The construct was in a vector and expressed in NSO host cells (p. 2155, col. 2, second paragraph). This construct encodes a “Troybody” (e.g., Abstract). Because it has the structure of an antibody, it inherently has a multimerizing unit which is the dimerizing human IgG3 Fc region (p. 2155, col. 1, third paragraph). It is stated (p. 2154, col. 2, third paragraph), “Troybodies have the advantage that all different professional APC expressing MHC class II molecules may be targeted.” It does not appear APCs were activated by the Troybodies; although, T cells were (p. 2156, col. 2, third paragraph and p. 2160, col. 2, second paragraph). The Troybodies were injected into mice and were, therefore, necessarily in a pharmaceutical composition with an acceptable carrier. It is discussed on p. 2161, col. 2, third paragraph, “However, Troybodies could also be used for induction of specific T cell tolerance to prevent or ameliorate autoimmune diseases. For example, Troybodies directed to APC in the thymus could induce central T cell tolerance to defined peptides. Similarly, Troybodies directed to appropriate APC, such as certain immature DC (52), could induce T cell anergy or regulatory, suppressive T cells.” Lunde et al. does not teach wherein the T cell epitope is a self-antigen.
Warren et al. teaches that in a phase I clinical trial in patients with multiple sclerosis (MS), a human autoimmune disease, tolerance to myelin basic protein (MBP), a self-antigen, by intraveneous injection of a peptide therefrom resulted in tolerance to the self-antigen, with absence of MBP autoantibodies lasting three to four months after the first injection (Abstract and Fig. 2).
It would have been obvious before the effective filing date of the instant invention to have substituted the allergen in Lunde et al. for the self-antigen of Warren et al. wherein the encoding nucleic acid sequence for the MBP peptide was used in the Troybody construct with the reasonable expectation that tolerance would have been induced as taught by Warren for intravenous administration of the peptide. Lunde et al. suggest treatment of an autoimmune disease with a Troybody through specific T cell tolerance. In view of this teaching by Lunde and the clinical trial of Warren et al., it would have been obvious to improve tolerance to a self-antigen by administration of a tolerance-inducing construct which is a polynucleotide encoding the Troybody, wherein the T cell epitope was the MBP peptide or another that induces T cell tolerance for treatment of an autoimmune disease, e.g., MS. The artisan of ordinary skill would have been motivated to use the Troybody format in order to avoid side effects from non-targeted administration. Substitution of one known element for another would have yielded predictable results to one of ordinary skill in the art. Also, it would have been obvious to have the Fc domain of the Troybody be that of a human IgG3 and a linker since the T cell epitope was introduced in the human IgG3 CH1 domain (p. 2155, col. 1, third paragraph).
The Supreme court has acknowledged that (KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 at 1390, U.S. 2007, emphasis added):
When a work is available in one field of endeavor, design incentives and other market forces can prompt variations of it, either in the same field or a different one. If a person of ordinary skill can implement a predictable varition..103 likely bars its patentability…if a technique has been used to improve one device, and a person of ordinary skill in the art would recognize that it would improve similar devices in the same way, using the technique is obvious unless its actual application is beyond that person’s skill. A court must ask whether the improvement is more than the predictable use of prior-art elements according to their established functions… (at 1390)
…the combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results (at 1395).
Conclusion
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Claire Kaufman
/Claire Kaufman/
Primary Examiner, Art Unit 1674
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