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 20 June 2024 has been entered in full.
Claims 1-20 are pending and under consideration in the instant application.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 17 December 2025; 21 November 2025; 20 February 2025; 04 November 2024; and 20 May 2024 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Claim Objections
1. Claims 1, 5, 13, and 17 are objected to because of the following informalities:
1a. In claim 1, line 4, after the word “(TL1A)”, the phrase “, wherein the antibody or antigen binding fragment comprises” should be inserted (and “comprising” deleted) (i.e., “binds to tumor necrosis factor ligand 1A (TL1A), wherein the antibody or antigen binding fragment comprises
1b. In claim 5, heavy chain and light chain variable region sequences are amino acid sequences, not sequence identifiers (SEQ ID NO:). Thus, for clarity, the claim should be amended to recite, for example, "comprises the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:104 and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 201".
1c. In claim 13, line 3, after “of an antibody or antigen binding fragment thereof”, the phrase “that binds to tumor necrosis factor ligand 1A (TL1A)” is missing and should be inserted.
1d. In claim 17, heavy chain and light chain sequences are amino acid sequences, not sequence identifiers (SEQ ID NO:). Thus, for clarity, the claim should be amended to recite, for example, "comprises the heavy chain comprises the amino acid sequence of SEQ ID NO: 505 and the light chain comprises the amino acid sequence of SEQ ID NO: 514".
Appropriate correction is required.
Claim Rejections - 35 USC § 112(d)
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.
2. Claim 14 is 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 14 recites the method of claim 13, wherein the heavy chain comprises an amino acid sequence at least 97%, 98%, or 99% identical to SEQ ID NO: 505 and the light chain comprising an amino acid sequence at least 96%, 97%, 98%, or 99% identical to SEQ ID NO: 514.
However, claim 13 from which claim 14 depends, already recites “a light chain comprising an amino acid sequence at least 96% identical to SEQ ID NO: 514”.
Therefore, the alternative limitation in claim 14 of “the light chain comprising an amino acid sequence at least 96%...identical to SEQ ID NO: 514” fails to further limit claim 13.
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.
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.
3. Claims 1, 2, 6-14, and 18-20 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.
Claim 1 is directed to a method of treating inflammatory bowel disease (IBD) in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of an antibody or antigen binding fragment thereof that binds to TL1A, wherein the antibody or antigen binding fragment thereof comprises: (a) a heavy chain variable region comprising an amino acid sequence at least 96% identical to SEQ ID NO: 104 and (b) a light chain variable region comprising an amino acid sequence at least 96% identical to SEQ ID NO: 201.
Claim 2 recites that the heavy chain variable region comprising an amino acid sequence at least 97%, 98%, or 99% identical to SEQ ID NO: 104 and the light chain variable region comprising an amino acid sequence at least 97%, 98%, or 99% identical to SEQ ID NO: 201.
Instant claim 13 also recites a method of treating IBD in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of an antibody or antigen binding fragment thereof comprising (a) a heavy chain comprising an amino acid sequence at least 96% identical to SEQ ID NO: 505 and (b) a light chain comprising an amino acid sequence at least 96% identical to SEQ ID NO: 514.
Claim 14 recites that the heavy chain comprising an amino acid sequence at least 97%, 98%, or 99% identical to SEQ ID NO: 505 and the light chain comprising an amino acid sequence at least 96%, 97%, 98%, or 99% identical to SEQ ID NO: 514.
The specification of the instant application teaches that one of skill will recognize that individual substitutions, deletions, or additions to a nucleic acid, peptide, polypeptide, or protein sequence which alters a single amino acid or a small percentage of amino acids in the encoded sequence is a “conservatively modified variant” wherein the alteration results in the substitution of an amino acid with a chemically similar amino acid and retain the ability to specifically bind the target antigen (page 220, [00258]). The specification points out that such conservatively modified variants are in addition to and do not exclude polymorphic variants, interspecies homologs, and alleles consistent with the disclosure (page 220, [00258]). The specification also discloses that the antibody and/or antigen-binding fragment can be a variant of a sequence described herein, e.g., a conservative substitution variant of an antibody polypeptide (pages 220-221, [00261]). The specification states that a variant may refer to a polypeptide substantially homologous to a native or reference polypeptide, but which has an amino acid sequence different from that of the native or reference polypeptide because of one or a plurality of deletions, insertions or substitutions (pages 220-221, [00261]). The specification teaches the generation of humanized variants of a previously humanized variant, termed “ASX” (pages 238-239, Example 1). The specification indicates that in the two strategies utilized, certain framework and CDR residues were mutated to determine impact on expression and solubility (pages 239-240, [00305]). The specification continues to teach that a limited number of mutations were examined and the mutations were predominantly restricted to the original murine CDR residue or mutations that were previously identified as enhancing binding affinity (pages 238-239, [00301-00303, 00305]). It is noted that the anti-TL1A antibody recited in the instant claims is named “A219” (per Table 1 at the top of page 245).
Instant claims 1 and 2 recite that the administered anti-TL1A antibody comprises heavy and light chain variable region sequence variants that have at least 96%, 97%, 98%, or 99% sequence identity to SEQ ID NOs: 104 and 201. Likewise, claims 13 and 14 recite that the administered anti-TL1A antibody comprises heavy and light chain sequence variants that have at least 96%, 97%, 98%, or 99% sequence identity to SEQ ID NOs: 505 and 514. These limitations are broadly interpreted by the Examiner as reading upon variants, fragments, and/or derivatives of the recited SEQ ID NOs. However, the specification does not teach any variant, fragment, or derivative of the heavy and light chain variable regions other than full-length amino acid sequences of SEQ ID NOs: 104 and 201. The specification also does not teach any variant, fragment, or derivative of the heavy and light chains other than the full-length amino acid sequences of SEQ ID NOs: 505 and 514.
The first paragraph of 35 U.S.C. § 112 "requires a 'written description of the invention' which is separate and distinct from the enablement requirement." Vas-Cath Inc. v. Mahurkar, 935 F.2d 1555, 1563 (Fed. Cir. 1991). An adequate written description of a chemical invention "requires a precise definition, such as by structure, formula, chemical name, or physical properties." University of Rochester v. G.D. Searle & Co., Inc., 358 F.3d 916, 927 (Fed. Cir. 2004); Regents of the Univ. of Cal. v. Eli Lilly & Co., Inc., 119 F.3d 1559, 1566 (Fed. Cir. 1997); Fiers v. Revel, 984 F.2d 1164, 1171 (Fed. Cir. 1993). "A description of what a material does, rather than of what it is, usually does not suffice." Rochester, 358 F.3d at 923; Eli Lilly, 119 F.3d at 1568. Instead, the "disclosure must allow one skilled in the art to visualize or recognize the identity of the subject matter purportedly described." Id. In addition, possession of a genus "may be achieved by means of a recitation of a representative number of [compounds]... falling within the scope of the genus." Eli Lilly, 119 F.3d at 1569. Possession may not be shown by merely describing how to obtain possession of members of the claimed genus. See Rochester, 358 F.3d at 927.
Thus, case law dictates that to provide evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include actual reduction to practice, disclosure of drawings or structure chemical formulas, sufficient relevant identifying characteristics (such as, complete or partial structure, physical and/or chemical properties, and functional characteristics when coupled with a known or disclosed structure/function correlation), methods of making the claimed product, level of skill and knowledge in the art, predictability in the art, or any combination thereof. In the instant case, the factors present in the claims for the administered anti-TL1A antibody are (1) structural characteristics that the antibody comprises heavy and light chain variable region sequence variants that have at least 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO: 104 and 201 or heavy and light chain sequence variants that have at least 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO: 505 and 514 and (2) functional characteristics of binding to TL1A and treating inflammatory bowel disease (IBD). There is no identification of any particular sequence or structure of the anti-TL1A antibody that must be conserved in order to provide the required binding and treatment functions listed. Thus, the claims are drawn to a genus of variant antibodies that bind TL1A.
The instant specification fails to disclose and there is no art-recognized correlation between the structure of the genus of variant anti-TL1A antibodies and the functions of binding specifically to TL1A and treating IBD. In other words, the specification does not teach the structure which results in an antibody that binds TL1A with the claimed required characteristics. The description of the anti-TL1A antibody termed, “A219” or “219” of the instant specification (top of page 245, Table 1) is not adequate written description of an entire genus of antibodies that bind TL1A and comprise heavy and light chain variable region sequence variants that have at least 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO: 104 and 201 or comprise heavy and light chain sequence variants that have at least 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO: 505 and 514. The disclosed antibodies that were generated alongside the claimed “A219” antibody are derived from the same parent antibody and are all similar to one another. Therefore, the disclosed antibodies are not representative of the breadth of the claims.
Furthermore, it is well established in the art that the formation of an intact antigen-binding site generally requires the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three CDRs which provide the majority of the contact residues for the binding of the antibody to its target epitope (Paul, William E., Fundamental Immunology, 3rd Edition, Raven Press, New York, Chapt. 8, pp. 292-295 (1993), under the heading “Fv Structure and Diversity in Three Dimensions”). The amino acid sequences and conformations of each of the heavy and light chain CDRs are critical in maintaining the antigen binding specificity and affinity which is characteristic of the parent immunoglobulin. It is expected that all of the heavy and light chain CDRs in their proper order and in the context of framework sequences which maintain their required conformation, are required in order to produce a protein having antigen-binding function and that proper association of heavy and light chain variable regions is required in order to form functional antigen binding sites (Paul, page 293, first column, lines 3-8 and line 31 to column 2, line 9 and lines 27-30). Even minor changes in the amino acid sequences of the heavy and light variable regions, particularly in the CDRs, may dramatically affect antigen-binding function as evidenced by Rudikoff et al. (Proc Natl Acad Sci USA. Vol 79, page 1979, 1982) and Zhang et al. (mAbs 7(1): 42-52, 2005; page 45, column 2)). Zhang et al. also indicate that minor variations in variable heavy and light chain CDR1s and CDR2s may lead to loss of antigen binding (page 46, column 1). It is noted that numerous other publications also acknowledge that conservative substitutions would in fact change the binding ability of antibodies, if not substantially reduce the affinity (see Vasudevan et al., Blood Cell Mol Dis 32: 176-181, 2004;; Brummell et al, Biochemistry 32: 1180-1187, 1993;; Kobayashi et al., Protein Engineering 12: 879-844, 1999;; Burks et al., PNAS 94: 412-417, 1997;; Jang et al., Mol Immunol 35: 1207-1217, 1998; Brorson et al. J Immunol 163: 6694-6701, 1999;; Colman, Res Immunol 145: 33-36, 1994). Thus, the state of the art recognized that it would be highly unpredictable that an anti-TL1A with any CDR/heavy chain variable region/light chain variable region variations as recited in the instant claims, would maintain its required conformation and would have the requisite antigen binding function.
Applicant is reminded that generally, in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus (Enzo Biochem, Inc. v. Gen-Probe Inc., 323 F.3d 956 (Fed. Cir. 2002); Noelle v. Lederman, 355 F.3d 1343 (Fed. Cir. 2004); Regents of the University of California v. Eli Lilly Co., 119 F.3d 1559 (Fed. Cir. 1997)). A patentee must disclose “a representative number of species within the scope of the genus of structural features common to the members of the genus so that one of skill in the art can visualize or recognize the member of the genus” (see Amgen Inc. v. Sanofi, 124 USPQ2d 1354 (Fed. Cir. 2017) at page 1358). An adequate written description must contain enough information about the actual makeup of the claimed products – “a precise definition, such as structure, formula, chemic name, physical properties of other properties, of species falling with the genus sufficient to distinguish the gene from other materials”, which may be present in “functional terminology when the art has established a correlation between structure and function” (Amgen page 1361).
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, 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). See also, Amgen Inc. v. Sanofi, 124 USPQ2d 1354 (Fed. Cir. 2017), relying upon Ariad Pharms., Inc. v. Eli Lily & Co., 94 USPQ2d 1161 (Fed Cir. 2010). 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). A “mere wish or plan” to obtain the claimed invention is not sufficient (Centocor Orth Biotech, Inc. v. Abbott Labs, 636 F.3d 1341 (Fed. Cir. 2011); Regents of the Univ. of California, 119 F.3d at 1566). In the instant application, the skilled artisan cannot envision the detailed chemical structure of the antibodies that bind anti-TL1A of the encompassed claims, 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 antibody is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483. In Fiddes, claims directed to mammalian FGF’s were found to be unpatentable due to lack of written description for that broad class. The specification provided only the bovine sequence.
Therefore, only an administered anti-TL1A antibody or antigen-binding fragment thereof that comprises (i) a heavy chain variable region comprising the amino acid of SEQ ID NO: 104 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 201 or (ii) a heavy chain comprising the amino acid of SEQ ID NO: 505 and a light chain comprising the amino acid sequence of SEQ ID NO: 514, but not the full breadth of the claims meets the written description provision of 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (see page 1115). See also Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1355 (Fed. Cir. 2010).
4. Claims 1, 2, 6-14, and 18-20 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of treating inflammatory bowel disease (IBD) in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of an anti-TL1A antibody or antigen-binding fragment thereof that comprises (i) a heavy chain variable region comprising the amino acid of SEQ ID NO: 104 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 201 or (ii) a heavy chain comprising the amino acid of SEQ ID NO: 505 and a light chain comprising the amino acid sequence of SEQ ID NO: 514, does not reasonably provide enablement for a method of treating IBD comprising administering an anti-TL1A antibody or antigen-binding fragment that comprises heavy and light chain variable region sequence variants that have at least 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO: 104 and 201 or comprise heavy and light chain sequence variants that have at least 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO: 505 and 514. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
Claim 1 is directed to a method of treating inflammatory bowel disease (IBD) in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of an antibody or antigen binding fragment thereof that binds to TL1A, wherein the antibody or antigen binding fragment thereof comprises: (a) a heavy chain variable region comprising an amino acid sequence at least 96% identical to SEQ ID NO: 104 and (b) a light chain variable region comprising an amino acid sequence at least 96% identical to SEQ ID NO: 201.
Claim 2 recites that the heavy chain variable region comprising an amino acid sequence at least 97%, 98%, or 99% identical to SEQ ID NO: 104 and the light chain variable region comprising an amino acid sequence at least 97%, 98%, or 99% identical to SEQ ID NO: 201.
Instant claim 13 also recites a method of treating IBD in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of an antibody or antigen binding fragment thereof comprising (a) a heavy chain comprising an amino acid sequence at least 96% identical to SEQ ID NO: 505 and (b) a light chain comprising an amino acid sequence at least 96% identical to SEQ ID NO: 514.
Claim 14 recites that the heavy chain comprising an amino acid sequence at least 97%, 98%, or 99% identical to SEQ ID NO: 505 and the light chain comprising an amino acid sequence at least 96%, 97%, 98%, or 99% identical to SEQ ID NO: 514.
The specification of the instant application teaches that one of skill will recognize that individual substitutions, deletions, or additions to a nucleic acid, peptide, polypeptide, or protein sequence which alters a single amino acid or a small percentage of amino acids in the encoded sequence is a “conservatively modified variant” wherein the alteration results in the substitution of an amino acid with a chemically similar amino acid and retain the ability to specifically bind the target antigen (page 220, [00258]). The specification points out that such conservatively modified variants are in addition to and do not exclude polymorphic variants, interspecies homologs, and alleles consistent with the disclosure (page 220, [00258]). The specification also discloses that the antibody and/or antigen-binding fragment can be a variant of a sequence described herein, e.g., a conservative substitution variant of an antibody polypeptide (pages 220-221, [00261]). The specification states that a variant may refer to a polypeptide substantially homologous to a native or reference polypeptide, but which has an amino acid sequence different from that of the native or reference polypeptide because of one or a plurality of deletions, insertions or substitutions (pages 220-221, [00261]). The specification teaches the generation of humanized variants of a previously humanized variant, termed “ASX” (pages 238-239, Example 1). The specification indicates that in the two strategies utilized, certain framework and CDR residues were mutated to determine impact on expression and solubility (pages 239-240, [00305]). The specification continues to teach that a limited number of mutations were examined and the mutations were predominantly restricted to the original murine CDR residue or mutations that were previously identified as enhancing binding affinity (pages 238-239, [00301-00303, 00305]). It is noted that the anti-TL1A antibody recited in the instant claims is named “A219” (per Table 1 at the top of page 245).
Instant claims 1 and 2 recite that the administered anti-TL1A antibody comprises heavy and light chain variable region sequence variants that have at least 96%, 97%, 98%, or 99% sequence identity to SEQ ID NOs: 104 and 201. Likewise, claims 13 and 14 recite that the administered anti-TL1A antibody comprises heavy and light chain sequence variants that have at least 96%, 97%, 98%, or 99% sequence identity to SEQ ID NOs: 505 and 514. These limitations are broadly interpreted by the Examiner as reading upon variants, fragments, and/or derivatives of the recited SEQ ID NOs. However, the specification does not teach any variant, fragment, or derivative of the heavy and light chain variable regions other than full-length amino acid sequences of SEQ ID NOs: 104 and 201. The specification also does not teach any variant, fragment, or derivative of the heavy and light chains other than the full-length amino acid sequences of SEQ ID NOs: 505 and 514.
The art recognizes that protein function cannot be predicted from structure alone (Bork, 2000, Genome Research 10:398-400; Skolnick et al., 2000, Trends in Biotech. 18(1):34-39, especially p. 36 at Box 2; Doerks et al., 1998, Trends in Genetics 14:248-250; Smith et al., 1997, Nature Biotechnology 15:1222-1223; Brenner, 1999, Trends in Genetics 15:132-133; Bork et al., 1996, Trends in Genetics 12:425-427). See also Tokuriki et al. (Current Opinion in Structural Biology 19: 596-604, 2009), who teach that mutations are generally destabilizing. For instance, Tokuriki et al. teach at page 596, right column, last paragraph, that “as mutations accumulate, protein fitness declines exponentially...or even more than exponentially...So by the time an average protein accumulates, on average, five mutations, its fitness will decline to <20%.” Further, at page 598, left column, last paragraph, Tokuriki et al. note that 50% of mutations are destabilizing, and >15% of mutations are highly destabilizing, and of the about 5% of mutations that are stabilizing values...many of these mutations result in inactive protein. Indeed, Tokuriki et al. conclude that “a more comprehensive understanding of how mutations affect protein fitness within living cells is needed, including their combined effects on function, thermodynamic and kinetic stability, and clearance through aggregation and degradation” (see page 602, left column, 2nd paragraph). Fenton et al. (Medicinal Chemistry Research 29:1133-1146, 2020) also state that while it is well known that most substitutions at conserved amino acid positions (which they call “toggle” switches) abolish function, it is also true that substitutions at nonconserved positions (which they call “rheostat” positions) are equally capable of affecting protein function. They conclude that substitutions at rheostat positions have highly unpredictable outcomes on the activities and specificities of protein-based drugs. Bhattacharya et al. (PLoS ONE 12(3): e0171355, 2017) state that the range of possible effects of even single nucleotide variations at the protein level are significantly greater than currently assumed by existing software prediction methods, and that correct prediction of consequences remains a significant challenge (p. 18). Furthermore, when multiple mutations are introduced, there is even less predictability. For evidence thereof, see Guo et al. (PNAS USA 101(25):9205-10, 2004), who state that the effects of mutations on protein function are largely additive (page 9207, left column, full paragraph 2). Fenton et al. supra, also acknowledge this (see abstract).
The amino acid sequences and conformations of each of the heavy and light chain CDRs are critical in maintaining the antigen binding specificity and affinity which is characteristic of the parent immunoglobulin. It is expected that all of the heavy and light chain CDRs in their proper order and in the context of framework sequences which maintain their required conformation, are required in order to produce a protein having antigen-binding function and that proper association of heavy and light chain variable regions is required in order to form functional antigen binding sites (Paul, page 293, first column, lines 3-8 and line 31 to column 2, line 9 and lines 27-30). Even minor changes in the amino acid sequences of the heavy and light variable regions, particularly in the CDRs, may dramatically affect antigen-binding function as evidenced by Rudikoff et al. (Proc Natl Acad Sci USA. Vol 79, page 1979, 1982) and Zhang et al. (mAbs 7(1): 42-52, 2005; page 45, column 2)). Zhang et al. also indicate that minor variations in variable heavy and light chain CDR1s and CDR2s may lead to loss of antigen binding (page 46, column 1).
Additionally, it is not well established in the art that all variable domains are amenable to modifications much less even conservative. Numerous publications acknowledge that conservative substitutions would in fact change the binding ability of antibodies if not substantially reduce the affinity. Brummell et al. (Biochemistry 32:1180-1187 (1993)) found that mutagenesis of the four HCDR3 contact residues for the carbohydrate antibody (Salmonella B O-polysaccharide) in no instance improved affinity but 60% of the mutants resulted in a 10-fold drop in binding constant (affinity electrophoresis value of 0.85), while still other mutants were lower (Table 1 and p. 1183, Col. 2, ¶2 to p. 1184, Col. 1, ¶1). Brummell demonstrate that no substitution retained antigen binding affinity similar to the wild type antibody despite targeted, conservative substitutions in known contact sites. Kobayashi et al. (Protein Engineering 12:879-844 (1999)) disclose that a scFv for binding a DNA oligomer containing a (6-4) photoproduct with Phe or Tyr substitutions at Trp 33 retained “a large fraction of the wild-type binding affinity, while the Ala substitution diminished antigen binding” (Table 1). However, Kobayashi et al. note “replacing Trp 33 with Phe or Ala alters the local environment of the (6-4) photodimer since binding is accompanied by large fluorescence increases that are not seen with the wild-type scFv” (p. 883, Col. 2, ¶3). Burks et al. (PNAS 94:412-417 (1997)) disclose scanning saturation mutagenesis of the anti-digoxin scFv (26-10) which also binds digitoxin and digoxigenin with high affinity and with 42-fold lower affinity to ouabain. 114 mutant scFvs were characterized for their affinities for digoxin, digitonin, digoxignenin and oubain. Histogram analysis of the mutants (Figure 2) reveals that “not all residues are optimized in even high affinity antibodies such as 26-10, and that the absence of close contact with the hapten confers higher plasticity, i.e., the ability to tolerate a wider range of substitutions without compromising binding (p. 415, Col. 2, ¶4- p. 416, ¶1).
Vasudevan et al. (Blood Cells Mol Diseases 32: 176-181, 2004) indicate that the single amino acid substitution at position 108 in the H3 loop of monoclonal antibody AP7.4 alters the shape of the loop and changes the binding specificity from integrin αIIbβ3 to integrin αvβ3 (page 177, column 1; Table 1; page 180 through page 181, column 1). Jang et al. (Molec. Immunol. 35:1207-1217 (1998)) teach that single amino acid mutations to the CDRH3 of a scFV derived from 2C10, an anti-dsDNA autoantibody, reduced the binding activity about 20-50% compared to the unmutated scFv (Table 4). Brorson et al. (J. Immunol. 163:6694-6701 (1999)) teach that single amino acid substitutions to the CDRs of IgM Abs for the bacterial protein, levan, are ablated. Colman (Research in Immunol. 145:33-36 (1994)) teaches that single amino acid changes within the interface of an antibody-antigen complex are important and that inasmuch as the interaction can tolerate amino acid sequence substitutions, “a very conservative substitution may abolish binding” while “in another, a non-conservative substitution may have very little effect on the binding” (p. 35, Col. 1, ¶1).
Additionally, the relevant art teaches that while CDR3 is important for antigen-binding, the conformations of other CDRs as well as framework residues also influence binding. MacCallum et al. (J Mol Biol. 262: 732-745, 1996) analyzed many different antibodies for interactions with antigen and state that although CDR3 of the heavy and light chain dominate, a number of residues outside the standard CDR definitions make antigen contacts (see page 733, right column) and non-contacting residues within the CDRs coincide with residues as important in defining canonical backbone conformations (see page 735, left col). De Pascalis et al. (The Journal of Immunology. 169: 3076-3084, 2002) demonstrate that grafting of the CDRs into a human framework was performed by grafting CDR residues and maintaining framework residues that were deemed essential for preserving the structural integrity of the antigen binding site (see page 3079, right column). Although abbreviated CDR residues were used in the constructs, some residues in all 6 CDRs were used for the constructs (see page 3080, left column). The fact that not just one CDR is essential for antigen binding or maintaining the conformation of the antigen binding site is underscored by Casset et al. (Biochemical and Biophysical Research Communications 307: 198-205, 2003), who constructed a peptide mimetic of an anti-CD4 monoclonal antibody binding site by rational design and the peptide was designed with 27 residues formed by residues from 5 CDRs (see entire document). Casset et al. also teach that although CDR H3 is at the center of most if not all antigen interactions, clearly other CDRs play an important role in the recognition process (page 199, left column) and this is demonstrated in this work by using all CDRs except L2 and additionally using a framework residue located just before the H3 (see page 202, left column). Vajdos et al. (J Mol Biol. 320: 415-428, 2002) teach that antigen binding is primarily mediated by the CDRs more highly conserved framework segments which connect the CDRs are mainly involved in supporting the CDR loop conformations and in some cases framework residues also contact antigen (page 416, left column). Holm et al. (Mol Immunology. 44: 1075-1084, 2007) describe the mapping of an anti-cytokeratin antibody where although residues in the CDR3 of the heavy chain were involved in antigen binding, unexpectedly a residue in CDR2 of the light chain was also involved (abstract). Chen et al. (J Mol Biol. 293: 865-881, 1999) describe high affinity variant antibodies binding to VEGF wherein the results show that the antigen binding site is almost entirely composed of residues from heavy chain CDRs, CDR-H1, H2, H3 (page 866). Wu et al. (J Mol Biol. 294: 151-162, 1999) state that it is difficult to predict which framework residues serve a critical role in maintaining affinity and specificity due in part to the large conformational change in antibodies that accompany antigen binding (page 152 left col) but certain residues have been identified as important for maintaining conformation. Sela-Culang et al. (Front Immunol 4: 302, 2013) also teach that it is now well-established that some of the framework residues may play an important role in antigen binding (page 7, column 1, last full paragraph through entirety of column 2).
The level of skill required to generate the antibodies is that of a molecular immunologist, and one of ordinary skill in the art would have been required to identify candidate amino acid residues for substitution in the heavy/light chain (variable) regions and/or CDR domains, perform the mutagenesis on the heavy/light chain (variable) regions and CDR domains, produce and express the modified antibodies, and measure binding characteristics (e.g., binding specificity, equilibrium dissociation constant (KD), dissociation and association rates (K off and Kon respectively), and binding affinity and/or avidity compared with the parent antibody). The technology to perform these experiments was available at the time of application filing, but the amount of experimentation required to generate even a single heavy/light chain variable region-modified and/or CDR-modified antibody meeting all of the claim limitations would not have been routine, much less could one of ordinary skill in the art predict that any one or combination of all the heavy/light chain variable region and/or CDR amino acid deletions, substitutions, or additions encompassed by the claims would result in just any antibody clone having retained the TL1A binding activity. Because of this lack of guidance in the instant specification, the extended experimentation that would be required to determine which amino acid sequences and modifications would be acceptable to retain occluding structural and functional activity, and the fact that the relationship between the sequence of a protein/peptide and its tertiary structure (i.e. its activity) are not well understood and are not predictable, it would require an undue amount of experimentation for one of skill in the art to arrive at the large number of heavy/light chain variable region polypeptides and heavy/light chain polypeptides of the encompassed claims. Applicant has not provided sufficient guidance to enable one of ordinary skill in the art to make and use the genus of anti-TL1A antibodies in the claims in a manner reasonably correlated with the scope of the claims. The scope of the claims must bear a reasonable correlation with the scope of enablement. See In re Fisher, 166 USPQ 19 24 (CCPA 1970).
Due to the large quantity of experimentation necessary to generate and screen antibody variants of the heavy/light chain variable regions of SEQ ID NOs: 104 and 201 and the heavy/light chains of SEQ ID NOs: 505 and 514 that are still capable of binding TL1A and treating IBD; the lack of direction/guidance presented in the specification regarding same; lack of working examples; the teachings of the prior art; the complex nature of the invention; the unpredictability of the effects of CDR and heavy/light chain alterations on antibody activity; and the breadth of the claims, undue experimentation would be required of the skilled artisan to use the claimed 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 (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.
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)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
5. Claims 1, 6, and 10-12 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by McGovern et al. (US 2018/0305459; cited on the IDS of 20 May 2024).
McGovern et al. teach a method of treating inflammatory bowel disease (IBD), ulcerative colitis, Crohn’s disease, and colonic fibrosis comprising administering an anti-TL1A antibody, meeting the limitations of instant claims 1 and 10-12 (page 2, [0016]; page 5, [0032-0033]); pages 6-7, [0045]). McGovern et al. disclose that the antibody may be humanized, meeting the limitations of instant claim 6 (page 7, [0045]).
McGovern et al. teach that the administered an anti-TL1A antibody comprises a heavy chain variable region amino acid sequence of SEQ ID NO: 150 and a light chain variable region amino acid sequence of SEQ ID NO: 151 (page 9, [0062]; Table 1, page 17). It is noted that the heavy chain variable region amino acid sequence of SEQ ID NO: 150 of McGovern et al. is 97.7% identical to the amino acid sequence of SEQ ID NO: 104 of the instant application, meeting the limitations of instant claim 1 (see sequence alignment, below). Additionally, the TL1A antibody light chain variable region amino acid sequence of SEQ ID NO: 151 of McGovern et al. is 96.6% identical to the amino acid sequence of SEQ ID NO: 201 of the instant application, meeting the limitations of instant claim 1 (see sequence alignment, below).
SEQ ID NO: 150 of McGovern et al.
Publication No. US20180305459A1
GENERAL INFORMATION
APPLICANT: CEDARS-SINAI MEDICAL CENTER
TITLE OF INVENTION: METHODS OF PREDICTING NON-RESPONSE TO ANTI-TNF TREATMENT IN SUBJECTS WITH INFLAMMATORY BOWEL DISEASE
FILE REFERENCE: 52388-729.201
CURRENT APPLICATION NUMBER: US/15/957,457
CURRENT FILING DATE: 2018-04-19
PRIOR APPLICATION NUMBER: 62/487,971
PRIOR FILING DATE: 2017-04-20
NUMBER OF SEQ ID NOS: 240
SEQ ID NO 150
LENGTH: 116
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide
Qy= instant SEQ ID NO: 104
Db=SEQ ID NO: 150 of McGovern et al.
Query Match 97.7%; Score 597; Length 116;
Best Local Similarity 96.6%;
Matches 112; Conservative 3; Mismatches 1; Indels 0; Gaps 0;
Qy 1 QVQLVQSGAEVKKPGASVKVSCKASGFDIQDTYMHWVKQRPGQGLEWMGRIDPASGHTKY 60
|||||||||||||||||||||||||||||||||||||:| ||||||||||||||||||||
Db 1 QVQLVQSGAEVKKPGASVKVSCKASGFDIQDTYMHWVRQAPGQGLEWMGRIDPASGHTKY 60
Qy 61 DPKFQVRVTITRDTSTSTVYLELSSLRSEDTAVYYCARSGGLPDVWGQGTTVTVSS 116
|||||||||:||||||||||:|||||||||||||||||||||||||||||||||||
Db 61 DPKFQVRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARSGGLPDVWGQGTTVTVSS 116
SEQ ID NO: 151 of McGovern et al.
Publication No. US20180305459A1
GENERAL INFORMATION
APPLICANT: CEDARS-SINAI MEDICAL CENTER
TITLE OF INVENTION: METHODS OF PREDICTING NON-RESPONSE TO ANTI-TNF TREATMENT IN SUBJECTS WITH INFLAMMATORY BOWEL DISEASE
FILE REFERENCE: 52388-729.201
CURRENT APPLICATION NUMBER: US/15/957,457
CURRENT FILING DATE: 2018-04-19
PRIOR APPLICATION NUMBER: 62/487,971
PRIOR FILING DATE: 2017-04-20
NUMBER OF SEQ ID NOS: 240
SEQ ID NO 151
LENGTH: 106
TYPE: PRT
ORGANISM: Artificial Sequence
OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide
Query Match 96.6%; Score 542; Length 106;
Best Local Similarity 96.2%;
Matches 102; Conservative 2; Mismatches 2; Indels 0; Gaps 0;
Qy= instant SEQ ID NO: 201
Db=SEQ ID NO: 151 of McGovern et al.
Qy 1 EIVLTQSPGTLSLSPGERATLSCRASSSVSYMYWYQQKPGQAPRPLIYATSNLASGIPDR 60
|||||||||||||||||||||||||||||||||||||||||||| |||||||||||:|||
Db 1 EIVLTQSPGTLSLSPGERATLSCRASSSVSYMYWYQQKPGQAPRLLIYATSNLASGVPDR 60
Qy 61 FSGSGSGTDFTLTISRLEPEDFAVYYCQQWEGNPRTFGGGTKLEIK 106
|||||||||:|||||||||||||||||||| |||||||||||||||
Db 61 FSGSGSGTDYTLTISRLEPEDFAVYYCQQWSGNPRTFGGGTKLEIK 106
McGovern et al. also teach an anti-TL1A antibody comprising a heavy chain variable region amino acid sequence of SEQ ID NO: 148 and a light chain variable region amino acid sequence of SEQ ID NO: 149 (page 9, [0062]). It is noted that the heavy chain variable region amino acid sequence of SEQ ID NO: 148 of McGovern et al. is 96.7% identical to the amino acid sequence of SEQ ID NO: 104 of the instant application. Meanwhile, the TL1A antibody light chain variable region amino acid sequence of SEQ ID NO: 149 of McGovern et al. is 97.3% identical to the amino acid sequence of SEQ ID NO: 201 of the instant application.
SEQ ID NO: 148 of McGovern et al.
Qy= instant SEQ ID NO: 104
Db=SEQ ID NO: 148 of McGovern et al.
Query Match 96.7%; Score 591; Length 116;
Best Local Similarity 94.8%;
Matches 110; Conservative 5; Mismatches 1; Indels 0; Gaps 0;
Qy 1 QVQLVQSGAEVKKPGASVKVSCKASGFDIQDTYMHWVKQRPGQGLEWMGRIDPASGHTKY 60
|||||||||||||||||||:|||||||||||||||||:| ||||||||||||||||||||
Db 1 QVQLVQSGAEVKKPGASVKLSCKASGFDIQDTYMHWVRQAPGQGLEWMGRIDPASGHTKY 60
Qy 61 DPKFQVRVTITRDTSTSTVYLELSSLRSEDTAVYYCARSGGLPDVWGQGTTVTVSS 116
|||||||||:||||||||||:|||||||||||||||:|||||||||||||||||||
Db 61 DPKFQVRVTMTRDTSTSTVYMELSSLRSEDTAVYYCSRSGGLPDVWGQGTTVTVSS 116
SEQ ID NO: 149 of McGovern et al.
Qy= instant SEQ ID NO: 201
Db=SEQ ID NO: 149 of McGovern et al.
Query Match 97.3%; Score 546; Length 106;
Best Local Similarity 98.1%;
Matches 104; Conservative 0; Mismatches 2; Indels 0; Gaps 0;
Qy 1 EIVLTQSPGTLSLSPGERATLSCRASSSVSYMYWYQQKPGQAPRPLIYATSNLASGIPDR 60
|||||||||||||||||||||||||||||||||||||||||||| |||||||||||||||
Db 1 EIVLTQSPGTLSLSPGERATLSCRASSSVSYMYWYQQKPGQAPRLLIYATSNLASGIPDR 60
Qy 61 FSGSGSGTDFTLTISRLEPEDFAVYYCQQWEGNPRTFGGGTKLEIK 106
|||||||||||||||||||||||||||||| |||||||||||||||
Db 61 FSGSGSGTDFTLTISRLEPEDFAVYYCQQWSGNPRTFGGGTKLEIK 106
The applied reference has a common inventor (Targan, S.) and Applicant (Cedars-Sinai Medical Center) with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2). This rejection under 35 U.S.C. 102(a)(2) might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C. 102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B) if the same invention is not being claimed; or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed in the reference and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement.
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.
Copending Application No. 18/316,811
6. Claims 1-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 7, 9, 20, 22, 26-28, 47, 80, 82, 85, and 90 of copending Application No. 18/316,811. Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are directed to treating inflammatory bowel disease in a subject comprising administering the same anti-TL1A antibody. Claim 1 of the instant application is directed to a method of treating inflammatory bowel disease (IBD) in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of an antibody or antigen binding fragment thereof that binds to TL1A, wherein the antibody or antigen binding fragment thereof comprises: (a) a heavy chain variable region comprising an amino acid sequence at least 96% identical to SEQ ID NO: 104 and (b) a light chain variable region comprising an amino acid sequence at least 96% identical to SEQ ID NO: 201.
Meanwhile, claim 7 of the ‘811 application recites a method treating Crohn’s disease or ulcerative colitis in a subject in need thereof comprising administering to the subject a therapeutically effective amount of an inhibitor of TL1A activity or expression…wherein the TL1A inhibitor is an antibody or antigen binding fragment thereof that binds to TL1A, comprising a heavy chain variable domain comprising an amino acid sequence at least about 97% identical to SEQ ID NO: 104, and a light chain variable domain comprising an amino acid sequence at least about 97% identical to SEQ ID NO: 201.
It is noted that the amino acid sequences of SEQ ID NOs: 104 and 201 of the ‘811 application are 100% identical to the amino acid sequences of SEQ ID NOs: 104 and 201 of the instant application.
Claim 5 of the instant application and claim 9 of the ‘811 application recite that the heavy chain variable domain comprises SEQ ID NO: 104 and the light chain variable domain comprises SEQ ID NO: 201.
Furthermore, claim 20 of the ‘811 application also recites a method of treating an inflammatory, a fibrotic, or a fibrostenotic disease or condition comprising administering a therapeutically effective amount of an inhibitor of TL1A, wherein the inhibitor is an antibody or antigen binding fragment thereof that binds to TL1A and comprises: a heavy chain variable region comprising SEQ ID NO: 301
X1VQLVQSGAEVKKPGASVKVSCKAS[HCDR1]WVX2QX3PGQGLEX4G[HCDR2]|RX5
TX6TX7DTSTSTX8YX9ELSSLRSEDTAVYYCAR[HCDR3]WGQGTTVTVSS, and
a light chain variable region comprising SEQ ID NO: 303
EIVLTQSPGTLSLSPGERATLSC[LCDR1]WYQQKPGQAPRX10X11TY[LCDR2]GIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC[LCDR3]FGGGTKLEIK, wherein each of X1-X11 is independently selected from A, R, N, D, C, Q, E, G, H, I, L, K, M, F, P, S, T, W, Y, or V.
Claim 26 of the ‘811 application recites that the HCDR1 is set forth by SEQ ID NO: 1, the HCDR2 is set forth by SEQ ID NO: 2, the HCDR3 is set forth by SEQ ID NO: 6, the LCDR1 is set forth by SEQ ID NO: 10, the LCDR2 is set forth by SEQ ID NO: 11, and the LCDR3 is set forth by SEQ ID NO: 12.
First, it is noted that the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 amino acid sequences of SEQ ID NOs: 1, 2, 6, 10, 11, and 12 are identical between the instant application and the ‘811 application (see below).
Qy=instant SEQ ID NO: 1
Db= SEQ ID NO: 1 of the ‘811 application
US-18-316-811-1
Query Match 100.0%; Score 58; DB 1; Length 10;
Best Local Similarity 100.0%;
Matches 10; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 GFDIQDTYMH 10
||||||||||
Db 1 GFDIQDTYMH 10
Qy=instant SEQ ID NO: 2
Db= SEQ ID NO: 2 of the ‘811 application
US-18-316-811-2
Query Match 100.0%; Score 94; DB 1; Length 17;
Best Local Similarity 100.0%;
Matches 17; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 RIDPASGHTKYDPKFQV 17
|||||||||||||||||
Db 1 RIDPASGHTKYDPKFQV 17
Qy=instant SEQ ID NO: 6
Db= SEQ ID NO: 6 of the ‘811 application
US-18-316-811-6
Query Match 100.0%; Score 37; DB 1; Length 7;
Best Local Similarity 100.0%;
Matches 7; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 SGGLPDV 7
|||||||
Db 1 SGGLPDV 7
Qy=instant SEQ ID NO: 10
Db= SEQ ID NO: 10 of the ‘811 application
US-18-316-811-10
Query Match 100.0%; Score 48; DB 1; Length 10;
Best Local Similarity 100.0%;
Matches 10; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 RASSSVSYMY 10
||||||||||
Db 1 RASSSVSYMY 10
Qy=instant SEQ ID NO: 11
Db= SEQ ID NO: 11 of the ‘811 application
US-18-316-811-11
Query Match 100.0%; Score 31; DB 1; Length 7;
Best Local Similarity 100.0%;
Matches 7; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 ATSNLAS 7
|||||||
Db 1 ATSNLAS 7
Qy=instant SEQ ID NO: 12
Db= SEQ ID NO: 12 of the ‘811 application
US-18-316-811-12
Query Match 100.0%; Score 55; DB 1; Length 9;
Best Local Similarity 100.0%;
Matches 9; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QQWEGNPRT 9
|||||||||
Db 1 QQWEGNPRT 9
Second, in the ‘811 application, when the CDR sequences and appropriate “X’s” are inserted into the “formula” of claim 20, the resulting heavy and light chain variable region sequences are identical to the amino acid sequences of SEQ ID NOs: 104 and 201 of the instant application (see comparisons, below).
Instant SEQ ID NO: 104 (CDRs in bold, underlined)
QVQLVQSGAEVKKPGASVKVSCKASGFDIQDTYMHWVKQRPGQGLEWMGRIDPASGHTKYDPKFQVRVTITRDTSTSTVYLELSSLRSEDTAVYYCARSGGLPDVWGQGTTVTVSS
SEQ ID NO: 301 of ‘811
X1VQLVQSGAEVKKPGASVKVSCKAS[HCDR1]WVX2QX3PGQGLEX4G[HCDR2]|RX5
TX6TX7DTSTSTX8YX9ELSSLRSEDTAVYYCAR[HCDR3]WGQGTTVTVSS
wherein each of X1-X11 is independently selected from A, R, N, D, C, Q, E, G, H, I, L, K, M, F, P, S, T, W, Y, or V
Instant SEQ ID NO: 201 (CDRs in bold, underlined)
EIVLTQSPGTLSLSPGERATLSCRASSSVSYMYWYQQKPGQAPRPLIYATSNLASGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQWEGNPRTFGGGTKLEIK
SEQ ID NO: 301 of ‘811
EIVLTQSPGTLSLSPGERATLSC[LCDR1]WYQQKPGQAPRX10X11TY[LCDR2]GIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC[LCDR3]FGGGTKLEIK
wherein each of X1-X11 is independently selected from A, R, N, D, C, Q, E, G, H, I, L, K, M, F, P, S, T, W, Y, or V
Instant claim 27 recites that the antibody comprises a human IgG1 heavy chain constant region. Claim 28 of the ‘811 application recites that the antibody comprises a human IgG1 Fc region.
Instant claim 13 recites treating IBD comprising administering an antibody that binds to TL1A, wherein the antibody comprises: (a) a heavy chain comprising an amino acid sequence at least 96% identical to SEQ ID NO: 505 and (b) a light chain comprising an amino acid sequence at least 96% identical to SEQ ID NO: 514. Meanwhile, claim 28 of the ‘811 application recites that the administered antibody of claim 7 comprises a heavy chain comprising any one of SEQ ID NOs: 501-513 or a light chain comprising SEQ ID NO: 514. It is noted that the amino acid sequence of SEQ ID NO: 505 of the ‘811 application is 100% identical to the amino acid sequence of SEQ ID NO: 505 of the instant application. The amino acid sequence of SEQ ID NO: 514 of the ‘938 application is also 100% identical to the amino acid sequence of SEQ ID NO: 514 of the instant application (see alignments, below).
Qy=instant SEQ ID NO: 505
Db= SEQ ID NO: 505 of the ‘811 application
US-18-316-811-505
Query Match 100.0%; Score 2375; DB 1; Length 446;
Best Local Similarity 100.0%;
Matches 446; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QVQLVQSGAEVKKPGASVKVSCKASGFDIQDTYMHWVKQRPGQGLEWMGRIDPASGHTKY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QVQLVQSGAEVKKPGASVKVSCKASGFDIQDTYMHWVKQRPGQGLEWMGRIDPASGHTKY 60
Qy 61 DPKFQVRVTITRDTSTSTVYLELSSLRSEDTAVYYCARSGGLPDVWGQGTTVTVSSASTK 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 DPKFQVRVTITRDTSTSTVYLELSSLRSEDTAVYYCARSGGLPDVWGQGTTVTVSSASTK 120
Qy 121 GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS 180
Qy 181 LSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVF 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 LSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVF 240
Qy 241 LFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYR 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 LFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYR 300
Qy 301 VVSVLTVLHQDWLNGKEYKCKVSNKALAAPIEKTISKAKGQPREPQVYTLPPSRDELTKN 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 VVSVLTVLHQDWLNGKEYKCKVSNKALAAPIEKTISKAKGQPREPQVYTLPPSRDELTKN 360
Qy 361 QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN 420
Qy 421 VFSCSVMHEALHNHYTQKSLSLSPGK 446
||||||||||||||||||||||||||
Db 421 VFSCSVMHEALHNHYTQKSLSLSPGK 446
Qy=instant SEQ ID NO: 514
Db= SEQ ID NO: 514 of the ‘811 application
RESULT 1
US-18-316-811-514
Query Match 100.0%; Score 1114; DB 1; Length 213;
Best Local Similarity 100.0%;
Matches 213; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EIVLTQSPGTLSLSPGERATLSCRASSSVSYMYWYQQKPGQAPRPLIYATSNLASGIPDR 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EIVLTQSPGTLSLSPGERATLSCRASSSVSYMYWYQQKPGQAPRPLIYATSNLASGIPDR 60
Qy 61 FSGSGSGTDFTLTISRLEPEDFAVYYCQQWEGNPRTFGGGTKLEIKRTVAAPSVFIFPPS 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 FSGSGSGTDFTLTISRLEPEDFAVYYCQQWEGNPRTFGGGTKLEIKRTVAAPSVFIFPPS 120
Qy 121 DEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTL 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 DEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTL 180
Qy 181 SKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 213
|||||||||||||||||||||||||||||||||
Db 181 SKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 213
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Copending Application No. 18/546,938
7. Claims 1-12 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 11, 31, 36,42, 54, and 214-228 of copending Application No. 18/546,938 in view of Poulton et al. (U.S. Patent 10,138,296; cited on the IDS of 20 May 2024).
Claim 1 of the instant application is directed to a method of treating inflammatory bowel disease (IBD) in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of an antibody or antigen binding fragment thereof that binds to TL1A, wherein the antibody or antigen binding fragment thereof comprises: (a) a heavy chain variable region comprising an amino acid sequence at least 96% identical to SEQ ID NO: 104 and (b) a light chain variable region comprising an amino acid sequence at least 96% identical to SEQ ID NO: 201.
Meanwhile, claim 1 of the ‘938 application recites a pharmaceutical composition comprising an antibody or antigen binding fragment thereof that binds to TL1A at a concentration greater than about 95 mg/ml. Claim 222 of the ‘938 application recites that the TL1A antibody or antigen binding fragment thereof comprises a heavy chain variable domain comprising an amino acid sequence at least 97% identical to any of one of SEQ ID NOs: 101-169 and a light chain variable domain comprising an amino acid sequence at least 97% identical to any one of SEQ ID NOs: 201-220.
It is noted that the amino acid sequence of SEQ ID NO: 104 of the ‘938 application is 100% identical to the amino acid sequence of SEQ ID NO: 104 of the instant application. The amino acid sequence of SEQ ID NO: 201 of the ‘938 application is also 100% identical to the amino acid sequence of SEQ ID NO: 201 of the instant application (see alignments, below).
Qy=instant SEQ ID NO: 104
Db= SEQ ID NO: 104 of the ‘938 application
US-18-546-938-104
Query Match 100.0%; Score 611; DB 1; Length 116;
Best Local Similarity 100.0%;
Matches 116; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QVQLVQSGAEVKKPGASVKVSCKASGFDIQDTYMHWVKQRPGQGLEWMGRIDPASGHTKY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QVQLVQSGAEVKKPGASVKVSCKASGFDIQDTYMHWVKQRPGQGLEWMGRIDPASGHTKY 60
Qy 61 DPKFQVRVTITRDTSTSTVYLELSSLRSEDTAVYYCARSGGLPDVWGQGTTVTVSS 116
||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 DPKFQVRVTITRDTSTSTVYLELSSLRSEDTAVYYCARSGGLPDVWGQGTTVTVSS 116
Qy=instant SEQ ID NO: 201
Db= SEQ ID NO: 201 of the ‘938 application
US-18-546-938-201
Query Match 100.0%; Score 561; DB 1; Length 106;
Best Local Similarity 100.0%;
Matches 106; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EIVLTQSPGTLSLSPGERATLSCRASSSVSYMYWYQQKPGQAPRPLIYATSNLASGIPDR 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EIVLTQSPGTLSLSPGERATLSCRASSSVSYMYWYQQKPGQAPRPLIYATSNLASGIPDR 60
Qy 61 FSGSGSGTDFTLTISRLEPEDFAVYYCQQWEGNPRTFGGGTKLEIK 106
||||||||||||||||||||||||||||||||||||||||||||||
Db 61 FSGSGSGTDFTLTISRLEPEDFAVYYCQQWEGNPRTFGGGTKLEIK 106
Additionally, the amino acid sequences of SEQ ID NOs: 104 and 201 in both applications comprise the same HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 amino acid sequences of SEQ ID NOs: 1, 2, 6, 10, 11, and 12, respectively (see bolded and underlined residues in the alignments directly above).
The claims of the ‘938 application do not recite that the pharmaceutical composition comprising the TL1A antibody is administered to treat a subject with inflammatory bowel disease.
Poulton et al. teach that the TL1A/DR3 signaling pathway has been implicated in several human biological systems, which are associated with human diseases (column 1, lines 55-57). Poulton et al. disclose that inhibiting TL1A interaction with DR3 has been shown to promote a therapeutic benefit in several immune-related conditions, such as experimental autoimmune encephalomyelitis, colitis, ulcerative colitis, Crohn’s disease, inflammatory bowel disease, skin disease, asthma, and arthritis (column 1, lines 59-64). Poulton et al. teach recombinant antibodies against TL1A and that such antibodies may be useful for treating a gastrointestinal disease, such as IBD, Crohn’s disease, ulcerative colitis, eosinophilic esophagitis, or irritable bowel syndrome (column 5, lines 12-27). More specifically, Poulton et al. disclose the treatment of rat models of inflammatory bowel disease with anti-TL1A antibodies (column 43, line 39 through column 44, line 54; Figures 12, 19, 20, 21, 22).
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to modify the pharmaceutical composition comprising TL1A antibodies of the claims of the ‘938 application by administering such antibodies to treat inflammatory bowel disease, as taught by Poulton et al. The person of ordinary skill in the art would have been motivated to make that modification because inhibiting the TL1A interaction with DR3 has been shown to promote a therapeutic benefit in several immune-related conditions, such as experimental autoimmune encephalomyelitis, colitis, ulcerative colitis, Crohn’s disease, inflammatory bowel disease, skin disease, asthma, and arthritis (Poulton et al., column 1, lines 59-64). The person of ordinary skill in the art reasonably would have expected success because Poulton et al. clearly indicate that the administration of anti-TL1A antibodies successfully treats IBD in rat models at the time the invention was made.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
8. Claims 1-12 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 4, 6-8, 12, 16, 21, 28, 30, 31, 36, 42, 46, 64, and 65 of copending Application No. 18/724,826. Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are directed to treating inflammatory bowel disease in a subject comprising administering the same anti-TL1A antibody. Claim 1 of the instant application is directed to a method of treating inflammatory bowel disease (IBD) in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of an antibody or antigen binding fragment thereof that binds to TL1A, wherein the antibody or antigen binding fragment thereof comprises: (a) a heavy chain variable region comprising an amino acid sequence at least 96% identical to SEQ ID NO: 104 and (b) a light chain variable region comprising an amino acid sequence at least 96% identical to SEQ ID NO: 201.
Meanwhile, claim 1 of the ‘826 application, for example, recites a method treating an inflammatory disease or condition in a subject comprising administering to the subject a first composition comprising a first therapeutically effective amount of an inhibitor of TL1A and administering to the subject a second composition comprising a second therapeutically effective amount of an inhibitor of IL-23. Claim 8 of ‘826 recites that the inflammatory disease or condition is selected from the group consisting of IBD, Crohn’s disease, ulcerative colitis, inderminate colitis, and moderately to severely active UC. Claim 16 recites that the inhibitor is an anti-TL1A antibody or antigen binding fragment thereof. Claim 42 recites that the anti-TL1A antibody comprises a heavy chain variable domain comprising an amino acid sequence at least 96% identical to any one of SEQ ID NOs: 101-169 and a light chain variable domain comprising an amino acid sequence at least 96% identical to any one of SEQ ID NOs: 201-220.
It is noted that the amino acid sequences of SEQ ID NOs: 104 and 201 of the ‘826 application are 100% identical to the amino acid sequences of SEQ ID NOs: 104 and 201 of the instant application. The HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 amino acid sequences of SEQ ID NOs: 1, 2, 6, 10, 11, and 12 are identical between the ‘826 application and the instant application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Copending Application No. 19/129,758
9. Claims 1-12 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, 6, 21, 40, 42, 83, 102, 103, 112, 115, 132, 135, and 142 of copending Application No. 19/129,758. Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are directed to treating inflammatory bowel disease in a subject comprising administering the same anti-TL1A antibody.
Claim 1 of the instant application is directed to a method of treating inflammatory bowel disease (IBD) in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of an antibody or antigen binding fragment thereof that binds to TL1A, wherein the antibody or antigen binding fragment thereof comprises: (a) a heavy chain variable region comprising an amino acid sequence at least 96% identical to SEQ ID NO: 104 and (b) a light chain variable region comprising an amino acid sequence at least 96% identical to SEQ ID NO: 201.
Meanwhile, claim 1 of the ‘758 application recites a method of treating an inflammatory, a fibrotic, or a fibrostenotic disease or condition in a subject, the method comprising: administering to the subject a therapeutically effective amount of an inhibitor of TL1A activity or expression, wherein the subject is selected based on a Predictive Response Index (PRI) above a cutoff, wherein the PRI is calculated from a combination of polymorphisms determined from a sample from the subject and the PRI above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of at least about 29%.
Claim 132 of the ‘758 application recites that the inflammatory, fibrotic, or fibrostenotic disease or condition comprises inflammatory bowel disease, Crohn's disease, obstructive Crohn's disease, ulcerative colitis, intestinal fibrosis, intestinal fibrostenosis, rheumatoid arthritis, or primary sclerosing cholangitis (meeting the limitations of instant claims 1 and 10-12).
Claim 103 of the ‘758 application recites that the anti-TL1A antibody comprises a heavy chain variable domain comprising an amino acid sequence at least 90% identical to any one of SEQ ID NOs: 101-135 or 310-312 and a light chain variable domain comprising an amino acid sequence at least 90% identical to any one of SEQ ID NOs: 201-206 or 303.
It is noted that the amino acid sequences of SEQ ID NOs: 104 and 201 of the ‘758 application are 100% identical to the amino acid sequences of SEQ ID NOs: 104 and 201 of the instant application. The HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 amino acid sequences of SEQ ID NOs: 1, 2, 6, 10, 11, and 12 are identical between the ‘758 application and the instant application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Copending Application No. 19/137,697
10. Claims 1-12 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 4, 6-8, 12, 16, 21, 28, 30, 31, 36, 41, 42, 46, 64, 67, and 68 of copending Application No. 19/137,697. Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are directed to treating inflammatory bowel disease in a subject comprising administering the same anti-TL1A antibody.
Claim 1 of the instant application is directed to a method of treating inflammatory bowel disease (IBD) in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of an antibody or antigen binding fragment thereof that binds to TL1A, wherein the antibody or antigen binding fragment thereof comprises: (a) a heavy chain variable region comprising an amino acid sequence at least 96% identical to SEQ ID NO: 104 and (b) a light chain variable region comprising an amino acid sequence at least 96% identical to SEQ ID NO: 201.
Meanwhile, claim 1 of the ‘697 application recites a method of treating an inflammatory disease or condition in a subject comprising administering to the subject a first composition comprising a first therapeutically effective amount of an inhibitor of TL1A and administering to the subject a second composition comprising a second therapeutically effective amount of an inhibitor of S1PR. Claim 8 of the ‘697 application recites that the inflammatory disease or condition is selected from the group consisting of IBD, ulcerative colitis, indeterminate colitis, and moderately to severely active ulcerative colitis. Claim 12 recites that the TL1A inhibitor is an anti-TL1A antibody. Lastly, claim 42 of the ‘697 application recites that the anti-TL1A antibody comprises a heavy chain variable domain comprising an amino acid sequence at least 96% identical to any one of SEQ ID NOs: 101-169 and a light chain variable domain comprising an amino acid sequence at least 96% identical to any one of SEQ ID NOs: 201-220.
It is noted that the amino acid sequences of SEQ ID NOs: 104 and 201 of the ‘697 application are 100% identical to the amino acid sequences of SEQ ID NOs: 104 and 201 of the instant application. The HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 amino acid sequences of SEQ ID NOs: 1, 2, 6, 10, 11, and 12 are identical between the ‘697 application and the instant application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Copending Application No. 19/145,064
11. Claims 1-12 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 4, 6-8, 12, 16, 21, 28, 30, 31, 36, 42, 46, and 61 of copending Application No. 19/145,064. Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are directed to treating inflammatory bowel disease in a subject comprising administering the same anti-TL1A antibody.
Claim 1 of the instant application is directed to a method of treating inflammatory bowel disease (IBD) in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of an antibody or antigen binding fragment thereof that binds to TL1A, wherein the antibody or antigen binding fragment thereof comprises: (a) a heavy chain variable region comprising an amino acid sequence at least 96% identical to SEQ ID NO: 104 and (b) a light chain variable region comprising an amino acid sequence at least 96% identical to SEQ ID NO: 201.
Meanwhile, claim 1 of the ‘064 application recites a method of treating an inflammatory disease or condition in a subject comprising administering to the subject a first composition comprising a first therapeutically effective amount of an inhibitor of TL1A and administering to the subject a second composition comprising a second therapeutically effective amount of an inhibitor of TNF. Claim 8 of the ‘064 application recites that the inflammatory disease or condition is selected from the group consisting of IBD, ulcerative colitis, indeterminate colitis, and moderately to severely active ulcerative colitis. Claim 12 recites that the TL1A inhibitor is an anti-TL1A antibody. Lastly, claim 42 of the ‘064 application recites that the anti-TL1A antibody comprises a heavy chain variable domain comprising an amino acid sequence at least 96% identical to any one of SEQ ID NOs: 101-169 and a light chain variable domain comprising an amino acid sequence at least 96% identical to any one of SEQ ID NOs: 201-220.
It is noted that the amino acid sequences of SEQ ID NOs: 104 and 201 of the ‘064 application are 100% identical to the amino acid sequences of SEQ ID NOs: 104 and 201 of the instant application. The HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 amino acid sequences of SEQ ID NOs: 1, 2, 6, 10, 11, and 12 are identical between the ‘064 application and the instant application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Copending Application No. 19/145,066
12. Claims 1-12 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 4, 6-8, 12, 16, 21, 28, 30, 31, 36, 41, 42, 46, 55, 58, and 59 of copending Application No. 19/145,066. Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are directed to treating inflammatory bowel disease in a subject comprising administering the same anti-TL1A antibody.
Claim 1 of the instant application is directed to a method of treating inflammatory bowel disease (IBD) in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of an antibody or antigen binding fragment thereof that binds to TL1A, wherein the antibody or antigen binding fragment thereof comprises: (a) a heavy chain variable region comprising an amino acid sequence at least 96% identical to SEQ ID NO: 104 and (b) a light chain variable region comprising an amino acid sequence at least 96% identical to SEQ ID NO: 201.
Meanwhile, claim 1 of the ‘066 application recites a method of treating an inflammatory disease or condition in a subject comprising administering to the subject a first composition comprising a first therapeutically effective amount of an inhibitor of TL1A and administering to the subject a second composition comprising a second therapeutically effective amount of an inhibitor of integrin. Claim 8 of the ‘066 application recites that the inflammatory disease or condition is selected from the group consisting of IBD, ulcerative colitis, indeterminate colitis, and moderately to severely active ulcerative colitis. Claim 12 recites that the TL1A inhibitor is an anti-TL1A antibody. Lastly, claim 42 of the ‘066 application recites that the anti-TL1A antibody comprises a heavy chain variable domain comprising an amino acid sequence at least 96% identical to any one of SEQ ID NOs: 101-169 and a light chain variable domain comprising an amino acid sequence at least 96% identical to any one of SEQ ID NOs: 201-220.
It is noted that the amino acid sequences of SEQ ID NOs: 104 and 201 of the ‘066 application are 100% identical to the amino acid sequences of SEQ ID NOs: 104 and 201 of the instant application. The HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 amino acid sequences of SEQ ID NOs: 1, 2, 6, 10, 11, and 12 are identical between the ‘066 application and the instant application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowable.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
Bamios et al. J Immunol 171: 4868-4874, 2003 (cited on the IDS of 20 May 2024; teach that TL1A is upregulated during chronic intestinal inflammation in ulcerative colitis and Crohn’s disease and in mouse models of chronic intestinal inflammation)
References that teach administration of anti-TL1A antibodies reduce colonic inflammation in mouse models (such as colitis)
Takedatsu et al. Gastroenterol 135: 552-567, 2008 (cited on the IDS of 20 May 2024)
Shih et al. Gastroenterol 142(5): S84, 2012 (cited on the IDS of 20 May 2024)
Shih et al. Nature 7(6): 1492-1503, 2014 (cited on the IDS of 20 May 2024)
Clarke et al. MABS 10(4): 664-677, 2018 (cited on the IDS of 20 May 2024)
Li et al. Pathol Res Practice 214: 217-227, 2018
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BEB
Art Unit 1647
12 August 2026
/BRIDGET E BUNNER/Primary Examiner, Art Unit 1647
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