DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of Application, Amendments and/or Claims
The amendment of 18 September 2024 has been entered in full. Claims 1, 6, 10, and 16 are amended. Claims 7-9, 11, 14-15, and 17-68 are cancelled. Claims 69-72 are added.
Claims 1-6, 10, 12, 13, 16, and 69-72 are under consideration in the instant application.
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, 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 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 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”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 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 statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
1. Specific deficiency - Sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.831(c). See Figures 7A, 19A, and 19B. Sequence identifiers for sequences (i.e., “SEQ ID NO:X” or the like) must appear either in the drawings or in the Brief Description of the Drawings.
Required response – Applicant must provide:
Amended drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required sequence identifiers (i.e., “SEQ ID NO:X” or the like) into the Brief Description of the Drawings, 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.
Claim Objections
2. Claims 2, 6, 10, and 16 are objected to because of the following informalities:
2a. Claim 2 uses the acronym “BTLA” without first defining what it represents. While the claims can reference acronyms, the material presented by the acronym must be clearly set forth at the first use of the acronym.
2b. In claim 10, in order to distinguish between the elements in the composition and the elements in the fusion protein, it is suggested that in line 1, after “comprising a”, insert either “(i)” or “(a)”. Similarly, in line 3, after the phrase “Fc protein and”, insert either “(ii)” or “(b)”.
2c. In claims 6 and 16, subpart (i), the term “G86T” seems to be a typographical error and should be amended to recite “G68T”.
Appropriate correction is required.
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.
3. Claims 4-6, 16, and 70-72 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 pre-AIA the applicant regards as the invention.
3a. Claims 4-6, 16, and 70 are rejected as being indefinite because the claims refer to “the HVEM protein” while also reciting specific mutations at specific amino acid positions. The metes and bounds of the claims cannot be determined because it is not clear what species or organism these mutations of HVEM are referring to. For instance, are the mutations in the human protein, murine protein, etc.? Without knowing the reference molecule, one skilled in the art would not be apprised of the correct locations of the amino acid substitutions.
3b. Claim 71 is rejected as being indefinite because the claim recites “[t]he fusion protein of claim 1, further comprising administering the fusion protein to subject having cancer or an autoimmune disorder or disorder”. However, claim 1, from which claim 71 depends, is directed to a fusion protein (product), and not a method. Claim 1 does not recite any method steps. One of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
3c. Claim 72 is rejected as being indefinite because the claim recites “[t]he pharmaceutical composition of claim 10, further comprising administering the pharmaceutical composition to a subject having cancer or an autoimmune disease or disorder”. However, claim 10, from which claim 72 depends, is directed to a pharmaceutical composition (product), and not a method. Claim 10 does not recite any method steps. One of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Claim Rejections - 35 USC § 102
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 for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 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.
4. Claims 1-3, 10, 12, 13, 71, and 72 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ware et al. (US 2013/0164306 (27 June 2013) or WO 2013/074738). It is noted that Ware et al. US 2013/0164306 and WO 2013/074738 have the same disclosure and thus, for brevity, relevant portions of US 2013/0164306 will be cited below.
Ware et al. teach a fusion protein comprising a non-naturally occurring HVEM protein with at least one mutation and an Fc protein, wherein the fusion protein comprises an extracellular domain of the HVEM protein, meeting the limitations of instant claims 1, 3, 12, and 13 (page 2, [0019-0020]; page 5, [0067]; page 6, [0069-0070], [0077]; [0082]; page 7, [0083-0092]; page 18, [0178]). Ware et al. indicate that the fusion protein is a BTLA agonist, meeting the limitations of instant claim 2 (page 18, [0177-0178]). Ware et al. also disclose a pharmaceutical composition comprising the non-naturally occurring HVEM protein, meeting the limitations of instant claim 10 (page 2, [0022]; page 8, [0096]).
5. Claims 1-3, 10, 12, 13, 71, and 72 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ware et al. (US 2010/0129389; 27 May 2010; hereinafter, “Ware2”).
Ware2 teach an HVEM protein that comprises an extracellular domain and one or more substitutions, including Y47F, Y61F, S58A, E65A, E76A, and R113A (page 7, [0047]). Ware2 disclose the construction of HVEM-Fc, a soluble dimeric form of HVEM (page 19, [0167]). Ware2 continue to teach that a mutation in the CRD1 region of HVEM-Fc at tyrosine-61 to alanine (Y61A), but not phenylalanine (Y61F), abolishes binding capability to BTLA without impacting cell surface expression, meeting the limitations of instant claims 1-3, 12, and 13 (page 19, [0168]; page 21, [0177]; Figures 2B, 2D; Figure 4G). Ware2 state that the invention further provides compositions, including pharmaceutical formulations, meeting the limitations of instant claim 10 (page 3, [0015]; page 16, [0131-0134]).
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.
6. Claim 1-3, 10, 12, 13, 69, 71, and 72 are rejected under 35 U.S.C. 103 as being unpatentable over Cheung et al. (US 2009/0311280) and Ware et al. (US 2010/0129389; 27 May 2010; hereinafter, “Ware2”).
Cheung et al. teach a human HVEM protein comprising an extracellular domain with a serine-58 to alanine (S58A) mutation that does not affect binding to BTLA (page 23, [0204, 0206]; page 25, [0227-0228]; Figure 6). Cheung et al. disclose that the mutant loses glycoprotein (gD) binding and reduces HSV-1 infection (page 25, [0228-0229]).
Cheung et al. does not teach a fusion protein comprising an HVEM mutant protein and an Fc protein.
Ware2 teach an HVEM protein that comprises an extracellular domain and one or more substitutions, including Y47F, Y61F, S58A, E65A, E76A, and R113A (page 7, [0047]). Ware2 disclose the construction of HVEM-Fc, a soluble dimeric form of HVEM (page 19, [0167]). Ware2 continue to teach that a mutation in the CRD1 region of HVEM-Fc at tyrosine-61 to alanine (Y61A), but not phenylalanine (Y61F), abolishes binding capability to BTLA without impacting cell surface expression (page 19, [0168]; page 21, [0177]; Figures 2B, 2D; Figure 4G). Ware2 state that the invention further provides compositions, including pharmaceutical formulations (page 3, [0015]; page 16, [0131-0134]).
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to modify the HVEM protein comprising a S58A mutation of Cheung et al. by fusing the mutant protein to an Fc protein as taught by Ware2. The person of ordinary skill in the art would have been motivated to make that modification because (i) the HVEM protein comprising a S58A mutation reduces HSV-1 infection (Cheung et al., page 25, [0228-0229]) and (ii) the Fc domain facilities solubility or inhibits aggregation of protein sequences lacking a membrane binding or transmembrane domain (Ware2, page 6, [0042]). The person of ordinary skill in the art reasonably would have expected success because similar mutant fusion proteins were already being generated (such as Ware2) at the time the invention was made. Therefore, the claimed invention as a whole was clearly prima facie obvious over the prior art.
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.
7. Claims 1-6, 10, 12, 13, 16, and 69-72 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No. 10,961,297. Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are directed to a fusion protein comprising a herpesvirus entry mediator (HVEM) protein and an Fc protein, wherein the HVEM protein comprises at least one mutation at amino acid residue 58, 68, 70, and/or 90.
Claim 1 of the instant application, for example, recites a fusion protein comprising a non-naturally occurring herpesvirus entry mediator (HVEM) protein and an Fc protein, wherein the fusion protein comprises an extracellular domain of the HVEM protein and the Fc protein. Claim 3 of the instant application recites that the fusion protein comprises at least one mutation in the HVEM. Claim 4 recites that the mutation is selected from S58R, S58K, S58Q, G68T, L70D, L70E, N70N, L70W, L90A, and a combination thereof. Claim 69 of the instant application recites that the mutation is a mutation of amino acid residue 58, 68, 70, and/or 90 of SEQ ID NO: 2.
Meanwhile, claim 1 of the ‘297 patent recites a fusion protein comprising an herpesvirus entry mediator (HVEM) protein and an Fc protein, wherein the HVEM protein comprises an extracellular domain and wherein the HVEM protein comprises at least one amino acid mutation selected from the group consisting of an amino acid mutation at residues 58, 68, 70, and 90 of SEQ ID NO:2, wherein the at least one amino acid mutation is selected from S58R, S58K, S58Q, G68T, L70D, L70E, L70N, L70W, and L90A of SEQ ID NO: 2.
It is noted that the amino acid sequence of SEQ ID NO: 2 of the ‘297 patent is 100% identical to the amino acid sequence of SEQ ID NO: 2 of the instant application.
Claims 6 and 16 of the instant application and claims 2 and 4 of the ‘297 patent recite the same HVEM protein mutations.
Claim 10 of the instant application and claim 4 of the ‘297 patent recite a pharmaceutical composition comprising the fusion protein.
Conclusion
No claims are allowable.
The art made of record and not relied upon is considered pertinent to applicant's disclosure:
Sedy et al. J Biol Chem 292(51): 21060-21070, 2017 (teachings of the instant specification)
References that teach HVEM protein mutations different from those recited in the instant claims:
Spear et al. U.S. Patent 6,291,207 (column 14)
Ware et al. US 2010/0104559 (page 12, [0105]; page 16, [0146])
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRIDGET E BUNNER whose telephone number is (571)272-0881. The examiner can normally be reached Monday-Friday 9:00 am-6:00 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Joanne Hama can be reached at (571) 272-2911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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BEB
Art Unit 1647
13 July 2026
/BRIDGET E BUNNER/Primary Examiner, Art Unit 1647
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