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 .
Continued Examination Under 37 CFR 1.114
1. 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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 March 5, 2026 has been entered. Claims 34-55 are pending and being examined. Claims 34, 48, 50 and 51 are amended. Claim 55 is new.
New Rejections
(necessitated by amendments)
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.
Claim Interpretation
2. New claim 55 recites: “The isolated antibody of claim 34, wherein (i) the heavy chain comprises a heavy chain variable region comprising an amino acid sequence as set forth in SEQ ID NO: 18; and (ii) the light chain comprises a light chain variable region comprising an amino acid sequence as set forth in SEQ ID NO: 14.” Thus, the claim can broadly encompass any (an) amino acid sequence found in (set forth in) SEQ ID NO: 18 or 14, that is as few as two consecutive amino acids found in SEQ ID NOs:18 and 14.
3. Claims 34-55 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 34 recites:
An isolated antibody that specifically binds B and T lymphocyte attenuator (BTLA), comprising
(i) a heavy chain comprising a heavy chain variable region comprising CDRH1, CDRH2 and CDRH3 have an amino acid sequence as set forth in SEQ ID NO: 1, 17, and 3, respectively; wherein the heavy chain comprises an amino acid sequence with up to 10 modifications from SEQ ID NO: 19; and
(ii) a light chain comprising a light chain variable region comprising CDRL1, CDRL2 and CDRL3 have an amino acid sequence as set forth in SEQ ID NO: 4, 12, and 6, respectively; wherein the light chain comprises an amino acid sequence with up to 10 modifications from SEQ ID NO: 16.
Claim 34 initially recites that the antibody comprises a heavy chain comprising three CDR SEQ ID NOs:1, 17, and 3, however, the claim subsequently recites that the heavy chain also comprises an amino acid sequence with up to 10 modifications from SEQ ID NO:19. SEQ ID NO:19 is the full heavy chain comprising CDR SEQ ID NOs:1, 17, and 3. Therefore, the claim language is confusing as to whether those 10 modifications encompass the CDR regions of the heavy chain, meaning that amino acid modification can occur within CDR SEQ ID NOs:1, 17, and 3, or whether those modification are occurring in addition to the CDRs present in the heavy chain.
The same logic applies to the language used for the light chain in claim 34. The claim language is confusing as to whether those 10 modifications encompass the CDR regions of the light chain, meaning that amino acid modification can occur within CDR SEQ ID NOs:4, 12, and 6, or whether those modification are occurring in addition to the CDRs present in the light chain.
Claim 55 does not clarify this language because claim 55 encompasses heavy and light chain variable region sequences that may have amino acid modifications in the CDR regions (see claim interpretation above).
The dependent claims are rejected for encompassing the rejected limitations of claim 34.
Clarification of language is required. See Examiner suggestions at the end of the office action.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
4. NOTE: For the sake of compact prosecution, the rejection under 35 U.S.C. 112(d) is made below by interpreting claim 34 as claiming antibodies limited to comprising full heavy chain SEQ ID NO:19 and full light chain SEQ ID NO:16, wherein SEQ ID NO:19 and 16 can comprise up to 10 amino acid modifications outside of the CDR sequences.
5. Claims 35-37 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 35 depends from claim 34. Claim 34 is limited to an antibody comprising a heavy chain variable region comprising CDRH1, CDRH2 and CDRH3 SEQ ID NOs:1, 17, and 3, respectively; wherein the heavy chain comprises an amino acid sequence with up to 10 modifications from full heavy chain SEQ ID NO:19. The antibody of claim 34 can be interpreted as comprising heavy chain SEQ ID NO:19 with up to 10 modifications. Claim 35 recites that the heavy chain of the antibody of claim 34 can have up to 11 amino acid substitutions in the Fc region, reciting that the heavy chain comprises one or more of 11 listed amino acid substitutions. Therefore, claim 35 comprises antibodies outside the scope of claim 34. Dependent claims are rejected for encompassing the rejected limitation of claim 35.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
Claim Interpretation
6. Claim 34 recites the antibody heavy chain comprises “an amino acid sequence with up to 10 modifications from SEQ ID NO:19” and the light chain comprises “an amino acid sequence with up to 10 modifications from SEQ ID NO:16”. First, the language of “an amino acid sequence …from SEQ ID NO:#” is interpreted to encompasses any (an) amino acid sequence from SEQ ID NO:19 or 16 that comprises as few as two consecutive amino acids taken from SEQ ID NOs:19 or 16. Second, the claim language broadly encompasses up to any 10 “modifications” from SEQ ID NO:19 or 16, including modifications encompassing chemical, phosphorylation, glycosylation, and consecutive stretches of amino acid deletions or insertions, wherein each consecutive stretch is counted as a separate “modification” (see specification at [0146] and [0341]).
7. Claims 34-55 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-28 of U.S. Patent No. 11,421,030. Although the claims at issue are not identical, they are not patentably distinct from each other because the US Patent claims a BTLA-binding antibody comprising the same CDR, VH, and VL sequences and properties instantly claimed, nucleic acid encoding the antibody, pharmaceutical composition comprising the antibody, method preparing the antibody, and method of treating an inflammatory disease, autoimmune disease, or proliferative disease by administering the antibody, rendering obvious the instant claims. The US Patent claims:
1. An antibody or an antigen-binding fragment thereof that specifically binds B and T Lymphocyte Attenuator (BTLA), wherein the antibody or antigen-binding fragment thereof comprises a heavy chain and a light chain, wherein:
(i) the light chain comprises a light chain variable region comprising three CDRs: CDRL1, CDRL2, and CDRL3, wherein (a) CDRL1 has the amino acid sequence as set forth in SEQ ID NO: 142; (b) CDRL2 has the amino acid sequence as set forth in SEQ ID NO: 143, with 0 to 1 amino acid modification at position 6 numbered according to SEQ ID NO: 143; and (c) CDRL3 has the amino acid sequence as set forth in SEQ ID NO: 210; and
(ii) the heavy chain comprises a heavy chain variable region comprising three CDRs: CDRH1, CDRH2, and CDRH3, wherein (a) CDRH1 has the amino acid sequence as set forth in SEQ ID NO: 205; (b) CDRH2 has the amino acid sequence as set forth in SEQ ID NO: 387, with 0 to 2 amino acid modifications at positions 5 and 7 numbered according to SEQ ID NO: 387; and (c) CDRH3 has the amino acid sequence as set forth in SEQ ID NO: 207.
2. The antibody or antigen-binding fragment thereof of claim 1, wherein the antibody or antigen-binding fragment thereof binds a residue of BTLA selected from the group consisting of: D52, P53, E55, E57, E83, Q86, E103, L106 and E92.
3. The antibody or antigen-binding fragment thereof of claim 1, wherein the antibody or antigen-binding fragment thereof agonizes human BTLA expressed on the surface of an immune cell.
4. The antibody or antigen-binding fragment thereof of claim 1, wherein the light chain variable region comprises an amino acid sequence having at least 90% identity to the amino acid sequence as set forth in SEQ ID NO: 378.
5. The antibody or antigen-binding fragment thereof of claim 4, wherein the heavy chain variable region comprises an amino acid sequence having at least 90% identity to the amino acid sequence as set forth in SEQ ID NO: 390.
6. The antibody or antigen-binding fragment thereof of claim 1, wherein the antibody or antigen-binding fragment thereof binds human BTLA at a KD of less than 10 nM, as determined by surface plasmon resonance at 37° C.
7. The antibody or antigen-binding fragment thereof of claim 1, wherein the antibody or antigen-binding fragment thereof binds human BTLA at a KD of less than 2 nM, as determined by surface plasmon resonance at 37° C.
8. The antibody or antigen-binding fragment thereof of claim 1, wherein the antibody or antigen-binding fragment thereof binds cynomolgus BTLA at a KD of less than 20 nM, as determined by surface plasmon resonance at 37° C.
9. The antibody or antigen-binding fragment thereof of claim 1, wherein the antibody or antigen-binding fragment thereof inhibits proliferation of T cells in vitro, as determined by a mixed lymphocyte reaction assay.
10. The antibody or antigen-binding fragment thereof of claim 1, wherein the antibody or antigen-binding fragment thereof does not inhibit binding of BTLA to herpes virus entry mediator (HVEM).
11. The antibody or antigen-binding fragment thereof of claim 1, further comprising a domain that binds to an Fc receptor.
12. The antibody or antigen-binding fragment thereof of claim 11, wherein said Fc receptor is FcγRIIB.
13. The antibody or antigen-binding fragment thereof of claim 1, wherein the antibody or antigen-binding fragment thereof is a humanized antibody.
14. The antibody or antigen-binding fragment thereof of claim 1, wherein the antibody or antigen-binding fragment thereof is a monoclonal antibody.
15. An isolated nucleic acid that comprises one or more nucleotide sequences encoding polypeptides capable of forming the antibody or antigen-binding fragment thereof of claim 1.
16. A host cell comprising one or more nucleic acid molecules encoding the amino acid sequence of a heavy chain and the amino acid sequence of a light chain, which when expressed are capable of forming the antibody or antigen-binding fragment thereof of claim 1.
17. A method, comprising culturing the host cell of claim 16 under conditions for production of the antibody or antigen-binding fragment thereof.
18. A method, comprising:
(1) providing a host cell comprising one or more nucleic acid molecules encoding the amino acid sequence of a heavy chain and the amino acid sequence of a light chain, which when expressed are capable of forming the antibody or antigen-binding fragment thereof of claim 1;
(2) culturing the host cell expressing the encoded amino acid sequences; and
(3) isolating the antibody or antigen-binding fragment thereof.
19. A pharmaceutical composition comprising a therapeutically effective amount of the antibody or antigen-binding fragment thereof of claim 1 and at least one pharmaceutically acceptable excipient.
20. A method of treating a BTLA-related disease or condition in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of the antibody or antigen-binding fragment thereof of claim 1.
21. The method of claim 20, wherein the disease or condition comprises an inflammatory disease, an autoimmune disease or disorder, or a proliferative disease or disorder.
22. The method of claim 20, wherein the disease or condition comprises Addison's disease, allergy, alopecia areata, amyotrophic lateral sclerosis, ankylosing spondylitis, anti-phospholipid syndrome, asthma, autoimmune haemolytic anaemia, autoimmune hepatitis, autoimmune pancreatitis, autoimmune polyendocrine syndrome, Behcet's disease, bullous pemphigoid, cerebral malaria, chronic inflammatory demyelinating polyneuropathy, coeliac disease, Crohn's disease, Cushing's Syndrome, dermatomyositis, diabetes mellitus type 1, eosinophilic granulomatosis with polyangiitis, graft versus host disease, Graves' disease, Guillain-Barre syndrome, Hashimoto's thyroiditis, Hidradenitis Suppurativa, inflammatory fibrosis, inflammatory bowel disease, juvenile arthritis, Kawasaki disease, leukemia, lymphoma, lymphoproliferative disorders, multiple sclerosis, myasthenia gravis, myeloma, neuromyelitis optica, pemphigus, polymyositis, primary biliary cholangitis, primary sclerosing cholangitis, psoriasis, psoriatic arthritis, rheumatoid arthritis, sarcoidosis, Sjögren's syndrome, systemic lupus erythematosus, Takayasu's arteritis, temporal arteritis, transplant rejection, transverse myelitis, ulcerative colitis, uveitis, vasculitis, vitiligo, or Vogt-Koyanagi-Harada Disease.
23. The method of claim 20, wherein the disease or condition comprises vasculitis, systemic lupus erythematosus, ulcerative colitis, inflammatory bowel disease, or graft versus host disease.
24. The antibody or antigen-binding fragment thereof of claim 1, wherein CRDL2 has no amino acid modifications as compared to SEQ ID NO: 143.
25. The antibody or antigen-binding fragment thereof of claim 1, wherein CRDH2 has an amino acid modification at position 5, position 7, or both, numbered according to SEQ ID NO: 387.
26. The antibody or antigen-binding fragment thereof of claim 25, wherein CDRL2 has no amino acid modifications as compared to SEQ ID NO: 143.
27. The antibody or antigen-binding fragment thereof of claim 25, wherein CDRH2 has Aspartic acid (D) at position 5, and Asparagine (N) at position 7, numbered according to SEQ ID NO: 387.
28. The antibody or antigen-binding fragment thereof of claim 1, wherein the light chain variable region comprises the amino acid sequence as set forth in SEQ ID NO: 378.
The BTLA-binding antibody claimed by the US Patent comprises a light chain variable region (VL) SEQ ID NO:378 that is 100% identical to instant VL SEQ ID NO:14 and comprises the same three CDRs (see sequence alignment below); and comprises a heavy chain variable domain (VH) SEQ ID NO:390 that is 100% identical to instant VH SEQ ID NO:18 except for the presence of Glu (E) at position 5 in CDR2 (see sequence alignment below), however the US Patent claims the VH CDR2 can comprise the E>D substitution mutation at position 5 in CDR2: (SIRSDGQTYYPDSVKG), rendering obvious instant VH SEQ ID NO:18. Therefore the antibody claimed by the US Patent comprises 100% of instant VH and VL SEQ ID NOs:18 and 14, respectively.
It is noted that instant heavy chain SEQ ID NO:19 comprises 100% of instant VH SEQ ID NO:18, and instant light chain SEQ ID NO:16 comprises 100% of instant VL SEQ ID NO:14. Therefore, the antibody claimed by the US Patent comprising 100% of instant VH and VL SEQ ID NOs:18 and 14, inherently comprises “an amino acid sequence from” SEQ ID NOs:19 and 16 as broadly encompassed by the instant claims.
Instant VH SEQ ID NO:18 aligned with US Patent 11,421,030 VH SEQ ID NO:390:
Qy= instant application
Db = US Patent
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304
630
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Instant VL SEQ ID NO:14 aligned with US Patent 11,421,030 VHLSEQ ID NO:378:
Qy= instant application
Db = US Patent
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324
624
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It is noted that US Patent 11,421,030 does not disclose or claim any full light chain sequence for the BTLA-binding antibody comprising instant SEQ ID NO:16, or any full heavy chain sequence comprising instant SEQ ID NO:19.
8. Examiner Suggestion:
Amend claim 34 to recite:
“…wherein the heavy chain comprises the amino acid sequence set forth in SEQ ID NO:19, having up to 10 amino acid substitutions within SEQ ID NO:19 excluding the CDRH1, CDRH2, and CDRH3 sequences;…
…wherein the light chain comprises the amino acid sequence set forth in SEQ ID NO:16, having up to 10 amino acid substitutions within SEQ ID NO:16 excluding the CDRL1, CDRL2, and CDRL3 sequences.”
Amend claim 55 to recite:
The isolated antibody of claim 34, wherein (i) the heavy chain comprises a heavy chain variable region comprising the amino acid sequence as set forth in SEQ ID NO: 18; and (ii) the light chain comprises a light chain variable region comprising the amino acid sequence as set forth in SEQ ID NO: 14.
9. Conclusion: No claim is allowed. All previous rejections of record are withdrawn in view of amendments. Applicant’s arguments are not drawn to the new rejections of record.
10. Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAURA B GODDARD whose telephone number is (571)272-8788. The examiner can normally be reached Mon-Fri, 7am-3:30pm.
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, Samira Jean-Louis can be reached at 571-270-3503. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Laura B Goddard/Primary Examiner, Art Unit 1642
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