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 .
Applicant's amendments and remarks, filed 06/15/2026, are acknowledged. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Status of Claims
Claims 33-38 are newly added.
Claims 12, 14, 17, 19, 28, 31, 33-38 are under examination.
Claims 1-11, 13, 15, 16, 18, 20-27, 29, 30, 32 are cancelled.
Priority
This application is a continuation of International Application No. PCT/US19/63770, filed November 27, 2019, which claims the benefit of US Provisional Application Serial Number 62/773,020, filed November 29, 2018, US Provisional Application Number 62/820,061, filed March 18, 2019, and US Provisional Application Number 62/849,622, filed May 17, 2019.
Claim Rejections - 35 USC § 112 1st paragraph
The following is a quotation of the first paragraph of 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.
This is a written description rejection.
Claims 12, 14, 17, 19, 28, 31, 33-38 are rejected under 35 U.S.C. 112, 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(s), at the time the application was filed, had possession of the claimed invention.
To satisfy the written-description requirement, the specification must describe every element of the claimed invention in sufficient detail so that one of ordinary skill in the art would recognize that the inventor possessed the claimed invention at the time of filing. Vas-Cath, 935 F.3d at 1563; see also Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572 (Fed. Cir. 1997) (patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that “the inventor invented the claimed invention”). Whether the specification shows that applicant was in possession of the claimed invention is not a single, simple determination, but rather is a factual determination reached by considering a number of factors. Factors to be considered in determining whether there is sufficient evidence of possession include: A) Partial structure; B) Physical and/or chemical properties; C) Functional characteristics; D) Known or disclosed correlation between structure and function; E) Method of making; and F) Combinations of A-E. See also MPEP 2163 and the 2011 Supplementary Guidelines to analysis under 35 USC 112 (Computer-Implemented Functional Claim Limitations).
Based on a consideration of the above factors, the level of skill and knowledge in the art, and the specification, the instant claims fail to meet the written description requirement for the following reasons:
Amended claim 12 and newly added claim 37 are directed to a method for treating Crohn’s disease in a subject by “administering to the subject a therapeutically effective amount of an anti-TL1A antibody, wherein the subject is identified as having a Crohn's Disease-Peripheral blood-mucosal (CD- PBmu) subtype by: (a) detecting an expression profile comprising an increase in a level of expression…in the biological sample obtained from the subject relative to a reference…profile; and (b) identifying the subject as having a CD-PBmu subtype based upon the expression profile that is detected in (a).”
In both claims, it is unclear how the subject is identified as having CD-PBMu subtype for the specific genes being claimed. Firstly, it is noted at the outset that the “wherein” clause recites product-by-process type limitations directed to how the patients have been identified (at a previous point in time) as well as past tense limitations directed to samples being “obtained” from a subject. However, these are simply inferred steps [not positive process limitations] and, as such, the claims appear to be missing essential subject matter. That being said, to the extent that applicant intends for the “detecting” and “identifying” steps to be positive process limitations, the above steps are not limited to any particular acts or operations and amount to functional language specifying desired results and/or specific functions, i.e. the claims broadly read on mentally analyzing data to detect expression profiles and identifying CD-PBMu subsets. A careful review of the specification, however, teaches that a defining hallmark for the CD-PBmu subtype, validated in an additional patient cohort (n=19), was profoundly downregulated expression of pro-inflammatory cytokines, chemokines and adhesion molecules following surgery [0279, FIGS. 4A-4B, Table 4]. However, this is not commensurate in scope with what is being claimed (i.e. the instant claims recite detecting an “increase in a level of expression” from the specific set of 15 genes (claim 12) and 27 genes (claim 37), which is a markedly different result that is not commensurate in scope with what is being claimed. In addition, the specification teaches performing RNA expression analysis using particular cells (purified CD3+ T-cells isolated from paired blood and mucosal tissue samples) from post-surgical CD patients and those without IBD, and using a particular bioinformatics tool (xCell) for analyzing and clustering transcriptional profiles to determine differences in transcriptomic signatures [0278, Figures 1A, 1B, 1C], wherein the CD-PBMu phenotype is defined by a distinctive peripheral T-cell subset composition [Figure 1D, 1E]. However, these disclosures are not commensurate in scope with what is presently being claimed and it is improper to import narrowing limitations into the claims. MPEP 2111.01. As such, the specification does not provide sufficient guidance as to the development, training, and/or validation of bioinformatics algorithms or predictive models for the full scope what is encompassed by the instant claims. Moreover, a review of the prior art and post-filing art teaches that such knowledge is not trivial for the following reasons:
Aran et al. (Genome Biology, 2017, 18:220, pp.1-14), which teaches a novel gene signature-based method and pipeline (xCell) for characterizing the tumor microenvironment using gene expression and cytometry data. In particular, unlike the claimed method, they use human cell type transcriptomes from various sources and apply a specific bioinformatics pipeline/protocol for gene expression enrichment analysis using a compendium of gene signature data, and perform validation of enrichment scores in expression profiles [Figure 1, pages 6-7, and “Methods” pages 10-12].
Potdar et al. (Gastroenterology, May 2021, Vol. 160, Issue 6, Supplement S-514) teaches determining a genetic panel for determining CD-PBmu based on a genetic association analyses of CD PBmu vs CD-PBT subjects, wherein combined genetic and transcriptomic pipeline was applied to identify a SNP-gene panel of 32 unique genes mapping to a total of 84 SNPs characterizing the CD-PBmu compared to CD-PBT subtype (Figure 1B). In this case, unlike the instant claims, the reference expression profile is related to CD-PBT and includes 32 genes mapping to distinct SNPs.
Sipos et al. (Disease Markers, 2011, 30, pp. 1–17) teaches peripheral blood based discrimination of ulcerative colitis and Crohn’s disease from nonIBD colitis by genomewide gene expression profiling. In particular, unlike the claimed method, Sipos teaches a molecular diagnostic assay using easily accessible peripheral blood using Affymetrix HGU133 Plus 2.0 microarrays for transcriptional profiles in blood/biopsy samples from UC, CD, noninflammatory bowel disease (nonIBD) colitis, and healthy patients. To identify differentially expressed features Significance Analysis of Microarrays was used along with ROC analysis. See entire.
Gonsky et al. (Gastroenterology, May 2019, Vol. 156, Issue 6, Supplement S-110–S-111), teaches determining and validating a CD-PBmu gene expression signature derived from whole blood (CD patients failing anti-TNF therapy, n=204) and the mucosal-like expression profile in peripheral CD-PBmu in data derived from ileal tissue (pediatric CD patients, 4 studies n> 600), and refining the results into a unique 44-gene panel to facilitate clinical application.
In summary, the cited art (and post-filing art) teaches that methods for the identification of CD-PBMu subtypes requires obtaining gene expression data from specific types of cells, and specific computational analysis techniques that are trained and validated on particular test and reference data sets, so that meaningful determinations of differential expression can be made. Therefore, after careful consideration, the instant specification fails to disclose that applicant had knowledge of the necessary information to achieve the claimed invention for the full scope of what is being claimed. For these reasons, the specification fails to meet the written description provision due to lack of information for performing the claimed functions. MPEP §2161.01- §2163.07(b).
Response to Arguments
Applicant’s arguments have been fully considered but are moot in view of the modified rejection, as set forth above, which is necessitated by amendment.
Claim rejections - 35 USC § 112, 2nd Paragraph
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 12, 14, 17, 19, 28, 31, 33-38 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention. Claims that depend directly or indirectly from claim(s) 12 is/are also rejected due to said dependency.
Amended claim 12 and newly added claim 37 recite “administering to the subject a therapeutically effective amount of an anti-TL1A antibody, wherein the subject is identified as having a Crohn's Disease-Peripheral blood-mucosal (CD- PBmu) subtype by: (a) detecting an expression profile comprising an increase in a level of expression…in the biological sample obtained from the subject relative to a reference…profile; and (b) identifying the subject as having a CD-PBmu subtype based upon the expression profile that is detected in (a).” In this case, the claimed “wherein” clause recites TWO product-by-process type limitations directed to how the patient sub-type is/was “identified” at some previous point in time (presumably before said “administering”) as well as a past-tense limitation (directed to a sample that was obtained from a subject). As a result, it is unclear what limiting effect of the claimed method is/are intended as limitations directed to the nature of the data, per se, have no limiting effect and claim scope is not limited by claim language that “suggests” but does not limit a claim to a particular function. See MPEP 2111.04. Stated differently, is the “wherein” clause further limiting the structural and/or biological conditions necessary for the subject being treated, how to decide whether to administer anti-TL1A, or otherwise. Notably a “‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’” Hoffer v. Microsoft Corp., 405 F.3d 1326, 1329, 74 USPQ2d 1481, 1483 (Fed. Cir. 2005). Clarification is requested via amendment. This rejection could be overcome, for example, by deleting the ‘wherein' clauses and replacing them with positive process limitations using active language, e.g. a) obtaining a sample from a patient…; b) detecting an expression profile…; c) identifying the subject as having….; and d) administering to the subject…an effective amount of an anti-TL1A antibody. This is only exemplary.
Claim 28 recites “adjusting a dosage amount or frequency of administration of the anti-TL1A antibody for the treatment of the CD, based on the CD-PBmu subtype.” In this case, the term “adjusting” is relative and the specification does not provide any limiting definitions, specific properties, or scoring criteria indicating the scope of this term. The specification [00178] teaches toxicity and therapeutic efficacy determined by standard pharmaceutical procedures including, but not limited to, the determination of the LD5o and the ED5o. However, such limitations are not commensurate in scope with what is being claimed. MPEP 2111.01. As a result, it is also unclear in what way the adjusting is performed “based on the based CD-PBmu subtype.” A review of the specification [0174, 0177] provides examples of daily dosages but does not provide any limiting definition that would serve to clarify what quantitative information and/or computational operations are encompassed to make decisions regarding the claimed “adjusting”. Clarification is requested via amendment.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PABLO S WHALEY whose telephone number is (571)272-4425. The examiner can normally be reached between 1pm-9pm EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Anita Coope can be reached at 571-270-3614. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/PABLO S WHALEY/Primary Examiner, Art Unit 3619
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