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 .
Claim Status
Applicant’s amendments and remarks, filed 09/30/2025, are acknowledged.
Claims 2-3 and 7-25 are canceled.
Claims 1, 4-6, and 26 are amended.
Claims 27-40 are new.
Claims 1, 4-6, and 26-40 are pending.
As such, claims 1, 4-6, and 26-40 are pending examination and currently under consideration for patentability under 37 CFR 1.104.
DETAILED ACTION
Continued Examination Under 37 CFR 1.114
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 09/30/2025 has been entered.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 09/30/2025 was filed after the mailing date of the final Office action on 07/01/2025. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Withdrawn Rejections
Applicant’s arguments, see pages 8-10, filed 09/30/2025, with respect to claims 1, 4-8, 21-24, and 26 rejected under 35 USC 112(b) as allegedly being indefinite have been fully considered and are persuasive. The issue regarding the claims comprising indefinite language have been sufficiently addressed through amendments to the claims. Further, Examiner acknowledges that claims 7, 8, and 21-24 are canceled thus rendering the rejection moot. As such, the rejection under 35 USC 112(b) is withdrawn.
Applicant’s arguments, see page 10, filed 09/30/2025, with respect to claims 1, 4-8, and 21-24 rejected under 35 USC 112(a) as allegedly incorporating new matter have been fully considered and are persuasive. The issue regarding the specification failing to disclose Applicant’s possession for the genus of “means for binding TL1A” have been sufficiently addressed through amendments to the claims. Further, Examiner acknowledges that claims 7, 8, and 21-24 are canceled thus rendering the rejection moot. As such, the new matter rejection under 35 USC 112(a) is withdrawn.
Further, the rejection of claims 1, 4-8, 21-24, and 26 under 35 USC 112(a) as allegedly failing to comply with the written description requirement is modified in favor of the new limitations added in the amendment filed 09/30/2025. Specifically, Examiner acknowledges that Applicant amended claim 1 to recite different polymorphisms and introduced new claims 27-40. Applicant’s arguments, see page 10, filed 09/30/2025, with respect to claims 1, 4-8, 21-24, and 26 rejected under 35 USC 112(a) have been fully considered.
Applicant’s remarks, see pages 10 and 11, filed on 09/30/2025, with respect to claims 1, 6, and 26 provisionally rejected on the grounds of nonstatutory double patenting as being allegedly unpatentable over claims 1-5, 7, 10-15, 20, 22, and 37 of copending Application No. 18/326,912 have been fully considered and are persuasive. Examiner acknowledges that the present claims were amended to recite different polymorphisms which are not recited in copending Application No. 18/326,912. As such, the provisional rejection of claims 1, 6, and 26 on the grounds of nonstatutory double patenting is withdrawn.
New Objections and Rejections Necessitated by Amendment
Claim Objections
Claims 36 and 39 are objected to because of the following informalities:
Claim 36: “anti-escherichia coli” should read “anti-Escherichia coli”.
Claim 39: “(Signal Transducer and Activator of Transcription (STAT) pathway” should read “.
Appropriate correction is required.
Claim Interpretation
Examiner acknowledges that “perianal involvement” refers to perianal disease, which is a disease that affects the tissue around the anus or the rectum of a patient that has been diagnosed using standard endoscopic, histologic, and radiographic features (see [0369] of the specification).
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1, 4-6, and 26-40 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.
Claims 1, 28, and 29 recite SNPs “imm_6_128020485A”, “imm_6_128029073A”, and “imm_6_138303642T” which corresponds to claimed rsid numbers “rs525850A”, “rs658795A”, and “rs768755T”, respectively, according to Table 1. Therefore the scope of the invention is unclear because the claim appears to overlap in scope. As such, claims 1 and 28-29, and their dependent claims, are rejected.
The term “modified” in claim is a relative term which renders the claim indefinite. The term “modified” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. While the specification recites “a modified Montreal classification was used: non-stricturing/non-penetrating (B1), stricturing (B2a), stricturing and penetrating (B2b), and isolated internal penetrating (B3)” (see [0362] of the specification), Applicant is reminded that although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). As such, one would not be apprised as to what is encompassed by the term “modified” in reference to the Montreal classification system.
Further, claim 27 recites the limitation “according to the modified Montreal classification system”. This limitation incorporates a reference in the claim. MPEP2173.05(s) states:
Where possible, claims are to be complete in themselves. Incorporation by reference “is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience.” Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993).
As such, claim 27 is rejected.
Claim 36 recites “Cbir1”, “anti-OmpC”, and “ASCA” within parentheticals. It is not clear if the language recited in the parentheses is limiting, or if it is only exemplary (e.g., are all anti-flagellin encompassed or only Cbir1).
The term “modulator” in claim 39 is a relative term which renders the claim indefinite. The term “modulator” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. While the specification discloses that the modulator of the gene or gene expression product is an agonist, a partial agonist, antagonist, partial antagonist, or an allosteric modulator (see [0011], [0012], [0014]-[0017], [0018], and [0019]), the specification does not define what would be considered a “partial” agonist or antagonist. Therefore, one would not be apprised as to what is encompassed by the term “modulator”. As such, claim 39 is rejected.
Claim Rejections - 35 USC § 112(a) Written Description
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 4-6, and 26-40 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed. The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the application. These include “level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention.”
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, disclosure of drawings, or by disclosure of relevant identifying characteristics, for example, structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the Applicants were in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
Claim 1 is drawn to a method of treating Crohn’s disease (CD) in a subject, the method comprising administering to the subject a therapeutically effective amount of an anti-tumor necrosis factor ligand 1A (atni-TL1A) antibody, wherein the subject has at least one polymorphism selected from the group consisting of imm_12_54907064A, imm_3_49968323G, imm_6_128020485A, imm_6_128027316G, imm_6_128027478G, imm_6_128029073A, imm_6_128029246A, imm_6_128029476C, imm_6_138299141G, imm_6_138299199C, imm_6_138302337G, imm_6_138303642T, lkg_2_25392861G, rs11161618A, rs17456596G,rs177665C, rs2314737G, rs351758A, rs4325270T, rs445417A, rs525850A, rs6074737A, rs635624C, rs658795A, rs666478G, rs684093G, rs7130717G, rs7416358G, rs768755T, rs7774349A, and rs936126A, and wherein the subject has non-stricturing and non-penetrating CD.
Claim 4 is drawn to the method of claim 1, wherein at least one of the polymorphisms is imm_6_128020485A, imm_6_128027316G, imm_6_128027478G, imm_6_128029073A, imm_6_128029246A, imm_6_128029476C, lkg_2_25392861G, rs17456596G, rs2314737G, rs445417A, rs525850A, rs635624C, rs666478G, rs684093G, rs7130717G, or rs936126A.
Claim 5 is drawn to the method of claim 1, wherein the polymorphism is detected by a process comprising: a) contacting a sample obtained from the subject with a nucleic acid sequence comprising a detectable moiety, wherein the nucleic acid sequence is capable of hybridizing to at least 20 contiguous nucleobases between nucleobase 16 and nucleobase 46 of at least one of SEQ ID NOS: 13-82; and b) detecting binding between the nucleic acid sequence and the at least 20 contiguous nucleobases between nucleobase 16 and nucleobase 46 of at least one of SEQ ID NOS: 13-82.
Claim 6 is drawn to the method of claim 1, wherein the polymorphism is detected by sequencing genetic information contained in a sample obtained from the subject.
Claim 26 is drawn to the method of claim 1, wherein the anti-TL1A antibody comprises an amino acid sequence of SEQ ID NOS: 356 and 357.
Claim 27 is drawn to the method of claim 1, wherein the non-stricturing and non-penetrating CD has a classification of B1 according to the modified Montreal classification system.
Claim 28 is drawn to the method of claim 1, wherein the subject has two or more polymorphisms selected from the group consisting of imm_12_54907064A, imm_3_49968323G, imm_6_128020485A, imm_6_128027316G, imm_6_128027478G, imm_6_128029073A, imm_6_128029246A, imm_6_128029476C, imm_6_138299141G, imm_6_138299199C, imm_6_138302337G, imm_6_138303642T, lkg_2_25392861G, rs11161618A, rs17456596G,rs177665C, rs2314737G, rs351758A, rs4325270T, rs445417A, rs525850A, rs6074737A, rs635624C, rs658795A, rs666478G, rs684093G, rs7130717G, rs7416358G, rs768755T, rs7774349A, and rs936126A.
Claim 29 is drawn to the method of claim 28, wherein the subject has three or more polymorphisms selected from the group consisting of imm_12_54907064A, imm_3_49968323G, imm_6_128020485A, imm_6_128027316G, imm_6_128027478G, imm_6_128029073A, imm_6_128029246A, imm_6_128029476C, imm_6_138299141G, imm_6_138299199C, imm_6_138302337G, imm_6_138303642T, lkg_2_25392861G, rs11161618A, rs17456596G,rs177665C, rs2314737G, rs351758A, rs4325270T, rs445417A, rs525850A, rs6074737A, rs635624C, rs658795A, rs666478G, rs684093G, rs7130717G, rs7416358G, rs768755T, rs7774349A, and rs936126A.
Claim 30 is drawn to the method of claim 1, wherein the CD is located in the ileal region of the subject.
Claim 31 is drawn to the method of claim 30, wherein the subject further has one or more polymorphisms selected from the group consisting of an of rs936126A, imm_6_128020485A, imm_6_128027316G, imm_6_128027478G, imm_6_128029073A, imm_6_128029246A, and imm_6_128029476C.
Claim 32 is drawn to the method of claim 1, wherein the CD is located in the ileocolonic region of the subject.
Claim 33 is drawn to the method of claim 32, wherein the subject further has one or both of an rs2314737G and rs445417A polymorphism.
Claim 34 is drawn to the method of claim 1, wherein the CD is located in the colonic region of the subject.
Claim 35 is drawn to the method of claim 34, wherein the subject further has one or more of an rs635624C, rs684093G, and lkg_2_25392861G polymorphism.
Claim 36 is drawn to the method of claim 1, wherein the subject further has seropositivity for one or more of anti-flagellin (Cbirl), anti-I2, anti-Escherichia coli outer membrane porin C (anti- OmpC), and anti-Saccharomyces cerevisiae (ASCA).
Claim 37 is drawn to the method of claim 1, wherein the CD is CD with perianal involvement.
Claim 38 is drawn to the method of claim 37, wherein the CD is located in the colonic region of the subject.
Claim 39 is drawn to the method of claim 1, further comprising administering to the subject a therapeutically effective amount of one of a modulator of prolactin signaling, autophagy, and the Janus Kinase (JAK)/(Signal Transducer and Activator of Transcription (STAT) pathway.
Claim 40 is drawn to the method of claim 1, wherein the CD is located in the ileal region, ileocolonic region, or colonic region of the subject.
The specification discloses of therapeutic agents useful for the treatment of a disease or condition, or symptom of the disease or condition, disclosed herein (see [0049]). Specifically, the specification discloses of TL1A modulators wherein the modulator can be an antagonist of TL1A, inhibits TL1A expression or activity, inhibits TL1A-DR3 binding, or indirectly influence the effects of TL1A on DR3 or TR6/DcR3 on TL1A or DR3 (see [0228]). Further, the specification discloses that inhibitors of TL1A activities include antagonists to the TL1A receptors, antagonists to TL1A antigen, and antagonists to gene expression products involved in TL1A mediated disease (see [0228]). Antagonists as disclosed herein, may include, but are not limited to, an anti-TL1A antibody, an anti-TL1A-binding antibody fragment, or a small molecule (see [0228]). Lastly, the specification recites several species of exemplary anti-TL1A antibodies (see [0229]-[0249] and Table 2).
The specification also discloses of the genotypic, clinical, and serological associations with severe CD in 1919 patients (see Example 1). Particularly, the specification discloses that CD patients with a high CD polygenic risk score (PRS) may benefit from an earlier and more aggressive treatment regiment, than CD patients with a high ulcerative colitis (UC) PRS (see [0366]). The specification also discloses that a pathway analysis tool (Ingenuity Pathway Analysis) was used on polymorphisms detected in Example to determine which molecular pathways play a role in severe CD (see Example 2). In Example 3, the specification discloses that an inflammatory disease is treated in a subject, by first, determining a genotype comprising a polymorphism… [where] a sample of whole blood is obtained from the subject (see [0372]). An assay is performed on the sample obtained from the subject to detect a presence or absence of the genotype by Illumina ImmunoArray or polymerase chain reaction (PCR) under standard hybridization conditions; an assay is performed on the sample obtained from the subject to detect a presence of a serological marker selected from the group consisting of ASCA, ANCA, anti-OmpC antibody, anti-I2 antibody, or anti-Cbir1 antibody by ELISA accordingly to manufacture instructions (see [0372]). Lastly, Examples 4-6 provide the criteria of for phase 1a-2a clinical trials (see pages 170-175). Specifically, Example 5 disclose that 10 patients positive for rs911605A are administered the antibody; 5-10 patients negative for the genotype are administered the antibody; patients are monitored in real-time; central ready of endoscopy and biopsy is employed, with readers blinded to point of time of treatment and endpoints (see [0385]).
However, the specification fails to adequately describe the method as recited in the claims. Specifically, the specification fails to identify the structure of the large genera of anti-TL1A antibodies or demonstrate that the representative number of species have successfully treated CD as recited in the claims. Additionally, the specification fails to demonstrate that Applicant was in possession of the large genera of prolactin signaling, autophagy, and the Janus Kinase (JAK)/Signal Transducer and Activator of Transcription (STAT) pathway modulators as claimed.
Furthermore, it is possible given the language of claim 26 which includes "an amino acid sequence of SEQ ID NOS: 356 and 357", that any two amino acids in sequence would suffice to meet the limitations of the claim. Because function of protein is dependent on the presence of each specific amino acid residue, and with the possibility of added or deleted amino acids, a wide variety of polypeptides, is encompassed by the instant claim. In addition the phrase “an amino acid sequence” allows any fragment, including any two amino acids in sequence, to be encompassed in the instant claim. This would in theory encompass any possible protein on earth. These peptides have no correlation between their structure and function. The claim requires that the peptide have binding activity for TL1A that would treat CD, but the specification provides no guidance to which peptides are capable of the required function.
Although the specification discloses exemplary anti-TL1A antibodies and modulators of certain pathways, the claims are not limited to these antibodies or modulators and are inclusive of any anti-TL1A antibody that has the functions of binding to TL1A, and any modulator of prolactin signaling, autophagy, and the Janus Kinase (JAK)/Signal Transducer and Activator of Transcription (STAT) pathway. This indicates that there are hundreds, if not thousands, of possible therapeutic agents encompassed by the claims. Thus, the claims encompass a vast genus of anti-TL1A antibodies and modulators that have the claimed functions. However, the specification provides limited guidance on the structure and steps required for maintaining the claimed function(s). Therefore, the specification does not provide adequate written description to identify the broad and variable genus of anti-TL1A therapeutic antibodies and modulators because, inter alia, the specification does not disclose a correlation between the necessary structure of the substance and the function(s) recited in the claims; and thus, the specification does not distinguish the claimed genus from others, except by function. Further, the specification fails to provide method steps that result in treating severe CD patients. Although the term antibody does impart some structure, the structure that is common to antibodies is generally unrelated to its specific binding function; therefore, correlation is less likely for antibodies than for other molecules. Accordingly, the specification does not define any structural features commonly possessed by the members of the genus, because while the description of an ability of the claimed substance may generically describe the molecule’s function, it does not describe the substance itself. A definition by function does not suffice to define the genus because it is only an indication of what the substance does, rather than what it is; therefore, it is only a definition of a useful result rather than a definition of what achieves the result. In addition, because the genus of substances is highly variable (i.e. each substance would necessarily have a unique structure, See MPEP 2434), the generic description of the substance is insufficient to describe the genus. Further, given the highly diverse nature of antibodies, particularly in CDRs, even one of skill in the art cannot envision the structure of an antibody by only knowing its binding characteristics. Thus, the specification does not provide substantive evidence for possession of this large and variable genus, encompassing a potentially massive number of anti-TL1A therapeutic antibodies and modulators or variants thereof claimed only be a functional characteristic(s) and/or partial structure.
As currently presented, the claims describe treating a candidate solely by function, i.e. binding to TL1A. Thus, the genus of “means for binding TL1A” are extremely broad because the claims recite generic and incompletely described agents. One of ordinary skill in the art would not be reasonably apprised of the structure of the claimed “means for binding TL1A” without adequate descriptions of its component parts or overall makeup. The generically claimed “means for binding TL1A” does not impart enough structural information to permit one of ordinary skill in the art to reasonably recognize or understand that Applicant was in possession of the full scope of the genus of “means for binding to TL1A” recited in the claims. For instance, without knowing the structure of the “means for binding to TL1A”, one would not be able to adequately describe the claimed drug. Therefore, the specification does not provide adequate written description to identify the broad and variable genus of “means for binding to TL1A” because, inter alia, the specification does not disclose a correlation between the necessary structure of the “means for binding to TL1A” and the function(s) recited in the claims; and thus, the specification does not distinguish the claimed genus from others, except by function.
A biomolecule sequence described only by a functional characteristic, without any known or disclosed correlation between that function and the structure of the sequence, normally is not sufficient identifying characteristics for written description purposes, even when accompanied by a method of obtaining the agent. The specification does not adequately describe the correlation between the chemical structure and function of the genus, such as structural domains or motifs that are essential and distinguish members of the genus from those excluded. Thus, the genus of antibodies has no correlation between their structure and function.
MPEP § 2163.03(V) states:
While there is a presumption that an adequate written description of the claimed invention is present in the specification as filed, In re Wertheim, 541 F.2d 257, 262, 191 USPQ 90, 96 (CCPA 1976), a question as to whether a specification provides an adequate written description may arise in the context of an original claim. An original claim may lack written description support when (1) the claim defines the invention in functional language specifying a desired result but the disclosure fails to sufficiently identify how the function is performed or the result is achieved or (2) a broad genus claim is presented but the disclosure only describes a narrow species with no evidence that the genus is contemplated. See Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1349-50 (Fed. Cir. 2010) (en banc). The written description requirement is not necessarily met when the claim language appears in ipsis verbis in the specification. "Even if a claim is supported by the specification, the language of the specification, to the extent possible, must describe the claimed invention so that one skilled in the art can recognize what is claimed. The appearance of mere indistinct words in a specification or a claim, even an original claim, does not necessarily satisfy that requirement. “Enzo Biochem, Inc. v. Gen-Probe, Inc., 323 F.3d 956, 968, 63 USPQ2d 1609, 1616 (Fed. Cir. 2002).
Applicant has not shown possession of a representative number of species of methods of treating CD in a subject comprising administering to the subject a therapeutically effective amount of an anti-TL1A antibody and further comprising administering a therapeutically effective amount of a prolactin signaling, autophagy, and the JAK/STAT pathway modulators, provided a genotype comprising at least one polymorphism associated with at least one of stricturing disease and internal penetrating disease is detected in a sample obtained from the subject. The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure "indicates that the patentee has invented species sufficient to constitute the gen[us]." See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004) ("[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated.") (MPEP 2163).
The instant claims do not fully describe the required method, or present any form of specific threshold or other standards that would allow the method to achieve the required function. Accordingly, the specification also does not provide adequate written description to identify the broad genus of the claimed anti-TL1A therapeutic antibodies or modulators, claimed only be a function characteristic(s) and not structures per se, because inter alia, it does not describe a sufficient number and/or a sufficient variety of representative species to reflect the breadth and variation within the claimed genus. Consequently, based on the lack of information within the specification, there is evidence that a representative number and a representative variety of the numerous anti-TL1A therapeutic antibodies and modulators had not yet been identified and thus, the specification represents little more than a wish for possession. Therefore, one of skill in the art would not conclude that Applicant was in possession of the broad and highly variable genus of anti-TL1A therapeutic antibodies and modulators claimed only by a partial structure and functional characteristic(s). Thus the method described by the instant specification encompasses an overly broad genus, and there is no correlation between the steps of the method, the structure of the therapeutic antibodies, and the functional outcome.
Tӧrӧk et al. (Pharmacogenomics (2008) 9(7), 881–893; previously submitted in Office Action mailed 02/29/2024) teach of pharmacogenetics of Crohn’s disease (see entire document). Tӧrӧk et al. disclose that considerable interindividual differences in efficacy and side effects of commonly used medications in Crohn’s disease are partly owing to genetic polymorphisms and many genetic variants have been studied in genes possibly involved in the metabolism or mechanism of action of therapeutic agents such as glucocorticosteroids (GCs), azathioprine/6-mercaptopurine, methotrexate, calcineurin inhibitors or anti-TNF agents (see Abstract). This is further established by Bank et al. (The Pharmacogenomics Journal (2014) 14, 526–534; previously submitted in Office Action mailed 02/29/2024) who disclosed that associations between functional polymorphisms in the NFκB signaling pathway and response to anti-TNF treatment in Danish patients with inflammatory bowel disease (see entire document). Bank et al. disclose that antitumor necrosis factor-α (TNF-α) is used for treatment of severe cases of inflammatory bowel diseases (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC); however, one-third of the patients do not respond to the treatment (see Abstract). Bank et al. disclose that 19 functional polymorphisms that alter the NFκB -mediated inflammatory response (TLR2 (rs3804099, rs11938228, rs1816702, rs4696480), TLR4 (rs5030728, rs1554973), TLR9 (rs187084, rs352139), LY96 (MD-2) (rs11465996), CD14 (rs2569190), MAP3K14 (NIK) (rs7222094)), TNF-α signaling (TNFA (TNF-a) (rs361525), TNFRSF1A (TNFR1) (rs4149570), TNFAIP3(A20) (rs6927172)) and other cytokines regulated by NFκB (IL1B (rs4848306), IL1RN (rs4251961), IL6 (rs10499563), IL17A (rs2275913), IFNG (rs2430561)) were associated with response to anti-TNF therapy among patients with CD, UC or both CD and UC (P ≤ 0.05)… suggesting that polymorphisms in genes involved in activating NFκB through the Toll-like receptor (TLR) pathways, genes regulating TNF-α signaling and cytokines regulated by NFκB are important predictors for the response to anti-TNF therapy among patients with IBD (see Abstract). As such, the art indicates there are several species of polymorphisms associated with severe CD and these polymorphisms can affect how therapies used for treating CD will work.
In 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), it is noted that to show invention, a patentee must convey in its disclosure that is “had possession of the claimed subject matter as of the filing date. Demonstrating possession “requires a precise definition” of the invention. To provide this precise definition” for a claim to a genus, 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 at page 1358). Also, it is not enough for the specification to show how to make and use the invention, i.e., to enable it (see Amgen at page 1361). 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). Most significant to the present case, the Court held that "knowledge of the chemical structure of an antigen [does not give] the required kind of structure-identifying information about the corresponding antibodies" (Amgen at 1361). The idea that written description of an antibody can be satisfied by the disclosure of a newly-characterized antigen “flouts basic legal principles of the written description requirement” as it “allows patentees to claim antibodies by describing something that is not the invention, i.e., the antigen... And Congress has not created a special written description requirement for antibodies” (Amgen at page 1362).
Abbvie v. Centocor (Fed. Cir. 2014) is also relevant to the instant claims. In Abbvie, the Court held that a disclosure of many different antibodies was not enough to support the genus of all neutralizing antibodies because the disclosed antibodies were very closely related to each other in structure and were not representative of the full diversity of the genus. The Court further noted that functionally defined genus claims can be inherently vulnerable to invalidity challenge for lack of written description support especially in technology fields that are highly unpredictable where it is difficult to establish a correlation between structure and function for the whole genus or to predict what would be covered by the functionally claimed genus.
The instant case has many similarities to AbbVie above. First, the claims clearly attempt to define the genus of anti-TL1A therapeutic antibodies and modulators by the functions of specifically treating CD. As noted by AbbVie above, functionally defined genus claims can be inherently vulnerable to invalidity challenge for lack of written description. Second, there is no information in the specification based upon which one of skill in the art would conclude that the disclosed species for which applicant has identified as having the recited functions would be representative of the entire genus. The specification discloses no structure to correlate with the function. Therefore, the specification provides insufficient written description to support the genus encompassed by the claim.
Furthermore, regardless whether a compound is claimed per se or a method is claimed that entails the use of the compound, the inventor cannot lay claim to that subject matter unless he can provide a description of the compound sufficient to distinguish infringing compounds from non-infringing compounds, or infringing methods from non-infringing methods. Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920-23, 69 USPQ2d 1886, 1890-93 (Fed. Cir. 2004).
Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear 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.) 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.)
Further, the skilled artisan cannot envision the detailed chemical structure of the encompassed antibodies, 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 for isolating it. The nucleic acid and/or protein itself is required. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993) and Amgen Inc. V. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. In Fiddes v. Baird, 30 USPQ2d 1481, 1483, claims directed to mammalian FGF's were found unpatentable due to lack of written description for the broad class. The specification provided only the bovine sequence.
Finally, University of California v. Eli Lilly and Co., 43 USPQ2d 1398, 1404. 1405 held that: ... To fulfill the written description requirement, a patent specification must describe an invention and does so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (1997); In re Gosteli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (" [T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed."). Thus, an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious," and by using “such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2d 1966.
It is 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 (Fundamental Immunology, 3rd Edition, Raven Press, New York, Chapter 8, pages 292-295, 1993; previously submitted in Office Action mailed 02/29/2024) teaches that 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 (See pages 293-295). While some publications acknowledge that CDR3 is important for antigen binding, the conformations of other CDRs as well as the framework are equally important in antigen binding. For example, MacCallum et al. (Journal of Molecular Biology, 262:732-745, 1996; previously submitted in Office Action mailed 02/29/2024) analyzed antigen-contacting residues and combining site shape of various antibodies and state that although CDR3 of the heavy chain and light chain dominate, a number of residues outside of the standard CDR definitions make antigen contacts (See page 733). MacCallum et al. teach that antigens tend to bind to the antibody residues located at the center of the combining site where the six CDRs meet (See abstract and page 742) and less central CDR residues are only contacted by large antigens (See page 733 and 735). MacCallum et al. further teach that non-contacting residues are important in defining "canonical" backbone conformations.
The fact that not just one CDR is essential for antigen binding or maintaining the conformation of the antigen binding site, is further underscored by Casset et al. (Biochemical and Biophysical Research Communications, 307:198-205, 2003; previously submitted in Office Action mailed 02/29/2024), which discuss the importance of multiple CDRs in antigen contact. Casset et al. teach that all antibodies have six CDR residues, all of which are more or less involved in antigen recognition (See page 199). Casset et al. teach that peptide mimetics of antibody combining sites have previously only targeted CDR H3, since this CDR is typically at the center of most, if not all, antigen interactions; however, this strategy is flawed since other CDRs play an important role in the recognition of antigen (See page 199). Casset et al. construct a peptide mimetic of an anti-CD4 monoclonal antibody, containing antigen contact residues from five CDR regions, except L2 and additionally using a framework residue located just before the H3 and show that the peptide has high binding to CD4, thus signifying the contribution of multiple CDRs, and not a single CDR, in antigen recognition (See page 202 and Figure 4).
Vajdos et al. (Journal of Molecular Biology, 2002 Jul 5;320(2):415-28; previously submitted in Office Action mailed 02/29/2024) additionally teaches that, “... Even within the Fv, antigen binding is primarily mediated by the complementarity determining regions (CDRs), six hypervariable loops (three each in the heavy and light chains) which together present a large contiguous surface for potential antigen binding. Aside from the CDRs, the Fv also contains more highly conserved framework segments which connect the CDRs and are mainly involved in supporting the CDR loop conformations, although in some cases, framework residues also contact antigen. As an important step to understanding how a particular antibody functions, it would be very useful to assess the contributions of each CDR side-chain to antigen binding, and in so doing, to produce a functional map of the antigen-binding site. For example, Brown et al. (J Immunol. 1996 May;156(9):3285-91 at 3290 and Tables 1 and 2), describes how the VH CDR2 of a particular antibody was generally tolerant of single amino acid changes, however the antibody lost binding upon introduction of two amino changes in the same region.
Further, Sela-Culang et al. 2013 (The structural basis of antibody-antigen recognition; Frontiers in Immunology 4(302):1-13; previously submitted in Office Action mailed 02/29/2024) teach the hypervariable loops within the variable domains of antibody polypeptides are widely assumed to be responsible for antigen recognition while the constant domains are believed to mediate effector activation, but that recent analysis indicates that their clear functional separation between the two regions is an over-simplification (see abstract). Sela-Culang et al. teach some residues within the CDRs may not participate in antigen binding and some residues outside the CDRs (e.g. in framework regions and in the constant domains) often contribute critically to the integration with the antigen (see abstract). Sela-Culang et al. teach understanding the role of each structural element is essential for successful engineering of binding polypeptides (e.g. page 2, left column). Sela-Culang et al. teach almost all of the residues predicted to be part of an epitope may be considered as correct predictors as they will bind to some antibodies but also are false predictors as they don’t bind to the others and accordingly that predicting that a residue is not in an epitope may be either a true negative or a false negative depending on the anybody considered (page 2, right column). Sela-Culang et al. teach each CDR has its own unique amino-acid composition different from the composition of the other CDRs and that each CDR has a unique set of contact preferences favoring certain amino acids over others (page 5-6, bridging). Sela-Culang et al. teach the combined action of all six CDRs is the evolutionary response of the immune system that enables the antibody polypeptide to recognize virtually any surface patch on the antigen (page 6).
The claims encompass an extremely large number of possible antibodies and modulators that have specific required functions. In the instant application, neither the art nor the specification provide a sufficient representative number of antibodies/modulators or a sufficient structure-function correlation to meet the written description requirements.
Additionally, regarding the encompassed anti-TL1A antibodies and modulators that are proteins and peptides, protein chemistry is one of the most unpredictable areas of biotechnology. This unpredictability prevents prediction of the effects that a given number or location of mutation will have on a protein (such as TNF or a cytokine) as taught by Skolnick et al. (Trends Biotechnol. 2000 Jan;18(1):34-9; previously submitted with the Office Action mailed 01/30/2025), sequence-based methods for predicting protein function are inadequate because of the multifunctional nature of proteins (see e.g. abstract). Further, just knowing the structure of the protein is also insufficient for prediction of functional sites (see e.g. abstract). Sequence to function methods cannot specifically identify complexities for proteins, such as gain and loss of function during evolution, or multiple functions possible within a cell (see e.g. page 34, right column). Skolnick advocates determining the structure of the protein, then identifying the functionally important residues since using the chemical structure to identify functional sites is more in line with how a protein actually works (see e.g. page 34, right column).
The sensitivity of proteins to alterations of even a single amino acid in a sequence are exemplified by Burgess et al. (J. Cell Biol. 111:2129-2138, 1990; previously submitted with the Office Action mailed 01/30/2025) who teach that replacement of a single lysine residue at position 118 of acidic fibroblast growth factor by glutamic acid led to the substantial loss of heparin binding, receptor binding and biological activity of the protein and by Lazar et al. (Mol. Cell. Biol., 8:1247-1252, 1988; previously submitted with the Office Action mailed 01/30/2025) who teach that in transforming growth factor alpha, replacement of aspartic acid at position 47 with alanine or asparagine did not affect biological activity while replacement with serine or glutamic acid sharply reduced the biological activity of the mitogen. These references demonstrate that even a single amino acid substitution will often dramatically affect the biological activity and characteristics of a protein.
Further, Miosge (Proc Natl Acad Sci U S A. 2015 Sep 15;112(37):E5189-98; previously submitted with the Office Action mailed 01/30/2025) teach that Short of mutational studies of all possible amino acid substitutions for a protein, coupled with comprehensive functional assays, the sheer number and diversity of missense mutations that are possible for proteins means that their functional importance must presently be addressed primarily by computational inference (see e.g. page E5189, left column). However, in a study examining some of these methods, Miosge shows that there is potential for incorrect calling of mutations (see e.g. page E5196, left column, top paragraph). The authors conclude that the discordance between predicted and actual effect of missense mutations creates the potential for many false conclusions in clinical settings where sequencing is performed to detect disease-causing mutations (see e.g. page E5195, right column, last paragraph). The findings in their study show underscore the importance of interpreting variation by direct experimental measurement of the consequences of a candidate mutation, using as sensitive and specific an assay as possible (see e.g. page E5197, left column, top paragraph). Additionally, Bork (Genome Research, 2000,10:398-400; previously submitted with the Office Action mailed 01/30/2025) clearly teaches the pitfalls associated with comparative sequence analysis for predicting protein function because of the known error margins for high-throughput computational methods. Bork specifically teaches that computational sequence analysis is far from perfect, despite the fact that sequencing itself is highly automated and accurate (p. 398, column 1). One of the reasons for the inaccuracy is that the quality of data in public sequence databases is still insufficient. This is particularly true for data on protein function. Protein function is context dependent, and both molecular and cellular aspects have to be considered (p. 398, column 2). Conclusions from the comparison analysis are often stretched with regard to protein products (p. 398, column 3). Further, although gene annotation via sequence database searches is already a routine job, even here the error rate is considerable (p. 399, column 2). Most features predicted with an accuracy of greater than 70% are of structural nature and, at best, only indirectly imply a certain functionality (see legend for table 1, page 399). As more sequences are added and as errors accumulate and propagate it becomes more difficult to infer correct function from the many possibilities revealed by database search (p. 399, paragraph bridging columns 2 and 3). The reference finally cautions that although the current methods seem to capture important features and explain general trends, 30% of those features are missing or predicted wrongly. This has to be kept in mind when processing the results further (p. 400, paragraph bridging cols 1 and 2).
One key issue is the prediction of protein function based on sequence similarity, which could be one way to identify the functional proteins that are useful in the instant claims. Kulmanov et al (Bioinformatics, 34(4), 2018, 660–668; previously submitted with the Office Action mailed 01/30/2025), teach that there are key challenges for protein function prediction methods (see e.g. page 661, left column). These challenges arise from the difficulty identifying and accounting for the complex relationship between protein sequence structure and function (see e.g. page 661, left column). Despite significant progress in the past years in protein structure prediction, it still requires large efforts to predict protein structure with sufficient quality to be useful in function prediction (see e.g. page 661, left column). Another challenge is that proteins do not function in isolation. In particular higher level physiological functions that go beyond simple molecular interactions will require other proteins and cannot usually be predicted by considering a single protein in isolation (see e.g. page 661, left column). Due to these challenges it is not obvious what kinds of features should be used to predict the functions of a protein and whether they can be generated efficiently for a large number of proteins, such as the vast genus of proteins and peptides that may be encompassed by the instant claims (see e.g. page 661, left column).
The state of the art regarding the structure-function correlation cannot be relied upon because functional characteristics of any peptide/protein are determined by its structure as evidenced by Greenspan et al. 1999 (Defining epitopes: It's not as easy as it seems; Nature Biotechnology, 17:936-937; previously submitted with the Office Action mailed 01/30/2025). Greenspan et al. teach that as little as one substitution of an amino acid (e.g. alanine) in a sequence results in unpredictable changes in the 3-dimenstional structure of the new peptide sequence which, in turn, results in changes in the functional activity such as binding affinity of the peptide sequence (page 936, 1st column). Greenspan et al. teach that contribution of each residue (i.e. each amino acid) cannot be estimated with any confidence if the replacement affects the properties of the free form of the molecule (page 936, 3rd column).
Given not only the teachings of Skolnick et al., Lazar et al., Burgess et al., and Greenspan et al., but also the limitations and pitfalls of using computational sequence analysis and the unknown effects of alternative splicing, post translational modification and cellular context on protein function as taught by Bork, the claimed anti-TL1A therapeutic antibodies and modulators could not be predicted based on sequence identity. Clearly, it could not be predicted that a polypeptide or a variant that shares only partial homology with a disclosed protein or that is a fragment of a given SEQ ID NO. will function in a given manner.
Regarding modulators that are small molecules, the prediction of binding to a target, much less the inhibitory activity, is highly unpredictable. According to Guido et al. (Curr Med Chem. 2008;15(1):37-46; previously submitted with the Office Action mailed 01/30/2025), accurately predicting the binding affinity of new drug candidates remains a major challenge in drug discovery (see page 37). There are a vast number of possible compounds that may bind any particular target, many of which have likely not been discovered. Relying on virtual screening also lends unpredictability to the art regarding identification of molecules that would be capable of the required functions of the instant claims. Guido et al. teach that there are two main complex issues with predicting activity for a small molecule: accurate structural modeling and/or correct prediction of activity (see page 40). As taught by Clark et al. (J. Med. Chem., 2014, 57 (12), pp 5023–5038; previously submitted with the Office Action mailed 01/30/2025), even when guided by structural data, developing selective structure-activity relationships has been challenging owing to the similarities of the enzymes (see page 5028). Therefore, it is impossible for one of skill in the art to predict that any particular encompassed small molecule therapeutic would function to inhibit a particular protein, especially a particular protein family member, or treat disease.
Regarding modulators that are nucleic acid-based therapeutics, the efficacy of any possible DNA or RNA based therapeutic modality is highly unpredictable. This unpredictability stems from an inability to predict the effects of any particular sequence the expression or function of any target. As taught by Aagaard et al. (Advanced Drug Delivery Reviews 59 (2007) 75–86; previously submitted with the Office Action mailed 01/30/2025), the development of RNAi based therapeutics faces several challenges, including the need for controllable or moderate promoter systems and therapeutics that are efficient at low doses (see page 79), the ability of an unpredictable number of sequences to stimulate immune responses, such as type I interferon responses (see page 79), competition with cellular RNAi components (see page 83), the side effect of suppressing off targets (see page 80), and challenging delivery (see page 83). The success of antisense strategies, including anti-RNA and anti-DNA strategies are also highly unpredictable. Warzocha et al. (Leukemia and Lymphoma (1997) Vol. 24. pp. 267-281; previously submitted with the Office Action mailed 01/30/2025) teach that the efficacy of antisense effects varies between different targeted sites of RNA molecules and three-dimensional RNA structures (see page 269), while DNA-targeting strategies have numerous problems including a restricted number of DNA sequences that can form triple helices at appropriate positions within genes and the inaccessibility of particular sequences due to histones and other proteins (see page 269). These references demonstrate that variation in RNA or DNA based therapeutics will often dramatically affect the biological activity and characteristics of the intended therapeutic. McKeague et al. (J Nucleic Acids. 2012;2012:748913. Epub 2012 Oct 24; previously submitted with the Office Action mailed 01/30/2025) teach that aptamers have particular challenges because unlike antibodies or molecular imprinted polymers, their tertiary structure is highly dependent on solution conditions and they are easily degraded in blood. Further, they have less chemical diversity than other antagonist molecules (see page 2), and have issues associated with determining the Kd measurements for a given molecule (see page 13).
Given the teachings of Aagaard et al, Warzocha et al, and McKeague et al, the claimed nucleic acid therapeutics could not be predicted based on the targets selected or similarities to the disclosed example therapeutics. Therefore, it is impossible for one of skill in the art to predict that any particular encompassed nucleic acid based therapeutic, such as oligonucleotide aptamers, RNAi molecules and antisense oligonucleotides, would function to decrease expression or function of a target gene or protein, or treat disease.
Taken together, the specification fails to support the breadth of the claims in which severe CD is treated with any TL1A therapeutic antibodies and modulators as recited in the claims. This is not indicative of the breadth of the claims and one of ordinary skill in the art would not be reasonably apprised that Applicant was in possession of the method of treating as claimed. 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).
The claimed invention as a whole may not be adequately described where an invention is described solely in terms of a method of its making coupled with its function and there is no described or art-recognized correlation or relationship between the structure of the invention and its function (see MPEP 2163). A patent specification must set forth enough detail to allow a person of ordinary skill in the art to understand what is claimed and to recognize that the inventor invented what is claimed. In the case of DNA, an adequate written description requires a precise definition, such as by structure, formula, chemical name, or physical properties, not a mere wish or plan for obtaining the claimed chemical invention (see Lilly, 119 F.3d at 1566 (quoting Fiers, 984 F.2d 15 1171 ). Because the specification does not describe the amino acid sequences nor any core structures for potentially numerous different antibody amino acid sequences which would have the recited dissociation constant, one of skill in the art would reasonably conclude that applicant was not in possession of the claimed genus of all anti-TL1A therapeutic antibodies and modulators.
A key role played by the written description requirement is to prevent “attempt[s] to preempt the future before it has arrived.” Ariad at 1353, (quoting Fiers v. Revel, 984 F.2d at 1171). Upholding a patent drawn to a genus of antibodies and modulators that includes members not previously characterized or described could negatively impact the future development of species within the claimed genus of antibodies and modulators.
While “examples explicitly covering the full scope of the claim language” typically will not be required, a sufficient number of representative species must be included to “demonstrate that the patentee possessed the full scope of the [claimed] invention.” Lizardtech v. Earth Resource Mapping, Inc., 424 F.3d 1336, 1345, 76 USPQ2d 1724, 1732 (Fed. Cir. 2005).
In the absence of sufficient recitation of distinguishing characteristics, the specification does not provide adequate written description of the claimed genus. One of skill in the art would not recognize from the disclosure that the applicant was in possession of the genus. Possession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features (see, Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 927, 69 USPQ2d 1886, 1895 (Fed. Cir. 2004); accord Ex Parte Kubin, 2007-0819, BPAI 31 May 2007, opinion at p. 16, paragraph 1). 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).
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).
Applicant’s Arguments
Applicant respectfully requests reconsideration and withdrawal of the rejection of the amended claims under 35 USC 112(a). Applicant indicates that claim 1 has been amended to remove the phrase “means for binding TL1A” and respectfully submits that claim 1 as amended, and all claims depending thereon, are supported by the specification.
Response to Arguments
Applicant’s arguments, see page 10, filed 01/09/2026, with respect to the rejection of claims 1, 4-8, 21-24, and 26 under 35 USC 112(a) for failing to comply with the written description requirement have been fully considered and are persuasive. Specifically, the examiner acknowledges that the language “means for binding TL1A” has been removed; therefore, the rejection has been withdrawn. However, upon further consideration, a new ground of rejection is made in view of the amendments made to the claims. First, claim 1 was amended to recite “a method of treating Crohn’s disease (CD) in a subject, the method comprising administering to the subject a therapeutically effective amount of an anti-tumor necrosis factor ligand 1A (atni-TL1A) antibody”. Further, claim 39 is drawn to the method of claim 1, further comprising administering to the subject a therapeutically effective amount of one of a modulator of prolactin signaling, autophagy, and the Janus Kinase (JAK)/(Signal Transducer and Activator of Transcription (STAT) pathway. As stated in the rejection, the claims solely describe the anti-TL1A antibody and modulators solely by their function without providing the structure of these therapeutic agents.
While Applicant is entitled to use functional language in the description of claimed agents, according to MPEP 2163, an invention described solely in terms of a method of making and/or its function may lack written descriptive support where there is no described or art-recognized correlation between the disclosed function and the structure(s) responsible for the function. This matches the facts here. The claims require specific functionality for the anti-TL1A antibody and modulators, but neither the instant disclosure, nor the art, provide description of the corresponding structure for that functionality or a representative number of species for the agents/components. For example, the anti-TL1A antibody is defined by their ability to bind to a specific protein. In both the base claims and the dependent claims, for at least one agent/component in each claim, the claims only describe what the agent/component does, not what the agents/components are. Even when given possible sequences from which to select a fragment of a peptide that would bind to TL1A or modulate prolactin signaling, autophagy, or the Janus Kinase (JAK)/(Signal Transducer and Activator of Transcription (STAT) pathway, the question remains about which one(s) of the encompassed antibodies/agents would actually perform the claimed function. While methods to identify the antibodies/agents with the required function may be routine in the art, the fact that any experimentation is required to figure out exactly what is encompassed necessarily means that applicant has not sufficiently described the claimed subject matter.
There are thousands of possible anti-TL1A and modulators encompassed by the instant claims. Furthermore, it is possible given the language of claim 26 which includes "an amino acid sequence of SEQ ID NOS: 356 and 357", that any two amino acids in sequence would suffice to meet the limitations of the claim. Because function of protein is dependent on the presence of each specific amino acid residue, and with the possibility of added or deleted amino acids, a wide variety of polypeptides, is encompassed by the instant claim. In addition the phrase “an amino acid sequence” allows any fragment, including any two amino acids in sequence, to be encompassed in the instant claim. This would in theory encompass any possible protein on earth. These peptides have no correlation between their structure and function. The claim requires that the peptide have binding activity for TL1A that would treat CD, but the specification provides no guidance to which peptides are capable of the required function.
One of skill in the art could not immediately envisage the encompassed species in each genus from the guidance provided in the instant specification and claims. Applicant has supplied a few species of anti-TL1A antibodies and modulators, some of which are not included in the sequences of the instant claims and may comprise at least part of the epitope to which the antibody binds. Further, the claims are not limited to these species. The claims encompass all anti-TL1A antibodies that can bind to TL1A and modulators that can modulate prolactin signaling, autophagy, or the Janus Kinase (JAK)/(Signal Transducer and Activator of Transcription (STAT) pathway to treat CD. This encompasses an extremely broad genus of therapeutic agents with a specific function, for which no correlating structure is provided.
The Federal Circuit has explained that a specification cannot always support expansive claim language and satisfy the requirements of 35 U.S.C. 112 "merely by clearly describing one embodiment of the thing claimed." LizardTech v. Earth Resource Mapping, Inc., 424 F.3d 1336, 1346, 76 USPQ2d 1731, 1733 (Fed. Cir. 2005). Describing a composition by its function alone typically will not suffice to sufficiently describe the composition. See Eli Lilly, 119 F.3 at 1568, 43 USPQ2d at 1406 (Holding that description of a gene' s function will not enable claims to the gene "because it is only an indication of what the gene does, rather than what it is."); see also Fiers, 984 F.2d at 1169-71, 25 USPQ2d at 1605-06 (discussing Amgen Inc. v. Chugai Pharm. Co., 927 F.2d 1200, 18 USPQ2d 1016 (Fed. Cir. 1991)). An adequate written description of a chemical invention also requires a precise definition, such as by structure, formula, chemical name, or physical properties, and not merely a wish or plan for obtaining the chemical invention claimed. See, e.g., Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 927, 69 USPQ2d 1886, 1894-95 (Fed. Cir. 2004) (The patent at issue claimed a method of selectively inhibiting PGHS-2 activity by administering a non-steroidal compound that selectively inhibits activity of the PGHS-2 gene product, however the patent did not disclose any compounds that can be used in the claimed methods. While there was a description of assays for screening compounds to identify those that inhibit the expression or activity of the PGHS-2 gene product, there was no disclosure of which peptides, polynucleotides, and small organic molecules selectively inhibit PGHS-2. The court held that "[w]ithout such disclosure, the claimed methods cannot be said to have been described.").
Additionally, the Federal Circuit explained in Amgen that when an antibody is claimed, 35 U.S.C. § 112(a) requires adequate written description of the antibody itself even when preparation of such an antibody would be routine and conventional. Amgen Inc., v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017). A key role played by the written description requirement is to prevent “attempt[s] to preempt the future before it has arrived.” Ariad at 1353, (quoting Fiers v. Revel, 984 F.2d at 1171). Upholding a patent drawn to a genus of antibodies that includes members not previously characterized or described could negatively impact the future development of species within the claimed genus of antibodies. In the instant application, neither the art nor the specification provide a sufficient representative number of antibodies or a sufficient structure-function correlation to meet the written description requirements.
Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it. The protein itself is required. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993) and Amgen Inc. V. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. In Fiddes v. Baird, 30 USPQ2d 1481, 1483, claims directed to mammalian FGF's were found unpatentable due to lack of written description for the broad class. The specification provided only the bovine sequence. Further, arguments relating to the isolation of an antibody with specific characteristics may be more appropriately directed to the invention' s enablement, since the method of isolating would detail how to make the invention. However, the enablement of the invention has not been rejected by the Examiner.
As such, the written description rejection is maintained.
Conclusion
No claims are allowed.
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/DANAYA L MIDDLETON/Examiner, Art Unit 1674
/VANESSA L. FORD/Supervisory Patent Examiner, Art Unit 1674