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 02/10/2026, 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 Rejections and/or objections not reiterated from previous office actions are hereby withdrawn.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 12, 14, 15, 17, 19, 23, 28, 31 are under examination.
Claims 1-11, 16, 18, 20-22, 24-27, 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.
Withdrawn Rejections
The rejection of claims 12, 14, 19, 31 under 35 U.S.C. 103 as being unpatentable over Siegal et al. (US9,068,003; Issued: 06/30/2015) in view of Brand et al. (Am J Physiol Gastrointest Liver Physiol, 290: G827–G838, 2006) and Nestec et al. (WO2013059732) is withdrawn in view of applicant’s amendments to the claims.
Information Disclosure Statement(s)
The information disclosure statement (IDS) document(s) submitted is in compliance with the provisions of 37 CFR 1.97. Accordingly, the IDS document(s) has/have been fully considered by the examiner.
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 12-15, 17, 19, 23, 28, 31, 32 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:
Claim 12 is directed to a method for treating Crohn’s disease in a subject by “administering…a therapeutic agent…; wherein the subject is identified as having a CD-PBmu subtype by: (a) detecting an expression profile comprising an increase in a level of expression of at least 10 or more genes in the biological sample, relative to a reference expression profile; wherein the at least 10 or more genes comprises ADAMTS1, LCN2, ADAM28, TPSB2, PPIAP30, GFPT2, KIT, T PLTP, MFSD2A, IL22,LMCD1, IL6, TBC1D9, CHAC1, SEPP1, SOD3, RAB13, LYZ,CPA3, SDS, DYRK3, DAB2, TBC1D8, CRYAB, TBC1D3, LRRC32, SERPING1, UBD,FABP1, SYK, ALDOB, SEMA6B, NANOGNB, DSE, FPR3, TNXB, OR4A5, DCN,CHST15, ADAMDEC1, HDC, RRAD, CIS, or PLA2G2A, or a combination thereof, 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 step of identifying a subject as having a CD-PBmu subtype is based upon detecting an increase in the expression level of 10 or more of the genes set forth above (relative to an expression profile). In other words, the invention requires a known correlation between the claimed group of genes and the particular disorder (CD-PB mucosal subtype). However, a review of the specification fails to provide any evidence that the alternative group of genes set forth above have the property of being associated with a CD-PBmu subtype, as claimed. Moreover, a review of the prior art and post-filing art teaches that such knowledge is not trivial for the following reasons:
Gonsky et al. (Gastroenterology, May 2019, Vol. 156, Issue 6, Supplement S-110–S-111), for example, 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.
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.
Sharat et al. (WO 2012154987) teaches methods for selecting an anti-TNF therapy regimen in an individual with Crohn's disease [Abstract, 0002, 0017-0020]. In particular, unlike the instant claims, Sharat teaches an array of mucosal markers (broadly interpreted as genes associated with CD-PBmu) comprising AREG, EREG, HB-EGF, HGF, NRG1, NRG2, NRG3, NRG4, BTC, EGF, IGF, TGF-a, VEGF-A, VEGF-B, VEGF-C, VEGF-D, FGF1, FGF2, FGF7, FGF9, TWEAK and combinations thereof [0020]
In summary, the art teaches that Crohn’s disease is unpredictable in both its clinical presentation and evolution, and classification of subtypes requires accurate information concerning genes as well as the presence of ulceration, edema, spasm, stricture, fistula formation, and associated inflammatory mass. Accordingly, there is no expectation from the knowledge in the art that each of the claimed genes would function in the same way in the claimed method; it is only in the context of this specification that it was disclosed that all members of this group may behave in the same way in the context of the claimed invention. The inventor must be able to describe the item to be patented with such clarity that the reader is assured that the inventor actually has possession and knowledge of the unique method that makes it worthy of patent protection. The reader can certainly appreciate the goal but establishing goals does not make a patent. As the Court of Appeals for the Federal Circuit stated in a case involving similar issues, an inadequate patent description that merely identifies a plan to accomplish an intended result “is an attempt to preempt the future before it has arrived.” Fiers v. Revel, 984 F.2d 1164, 1171 (Fed. Cir.1993). As a result the amended claims fail to provide a known or disclosed correlation between structure and function.
In addition, the administering step recites a therapeutic agent that comprises a “modulator and/or antagonist of TNF Superfamily Member 15 (TL1A), or the gene encoding TL1A (TNFSF15). In this case, one of ordinary skill in the art of drug design would recognize that modulators and antagonists encompass entirely different compounds with different functional limitations, and that different modulators effect different genes. For example, antagonists include drugs that bind to receptors and block the action of agonists, e.g. antibodies, whereas modulators include substances that alter the activity or conformation of a receptor without activating it. At best, the instant specification teaches anti-TL1A antibodies [0137-0138]. However, this is not provide support for the full scope of the “therapeutic agent” presently embraced by the claims.
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).
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 12-15, 17, 19, 23, 28, 31, 32 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.
Claim 12 recites “administering…a therapeutic agent, wherein the therapeutic agent comprises a modulator and/or antagonist of TNF Superfamily Member 15 (TL1A), or the gene encoding TL1A (TNFSF15).” It is unclear as to the metes and bounds of the “therapeutic agent” being claimed. As discussed above, the artisan would recognize that a modulator and antagonist encompass distinct compounds and functions. The specification teaches antagonists that include anti-TL1A antibodies [0137-0138], for example. However, it is improper to import narrowing limitations into the claims. MPEP 2111.01. Clarification is requested via amendment. To advance prosecution, the examiner suggests amending the claim to recite “…administering to the subject a therapeutically effective amount of a therapeutic agent that modulates the activity or expression of the TL1A gene, wherein the agent comprises anti-TL1A antibodies”. This is only an example.
Claim 12 recites to the term “CD-PBmu subtype”. It is unclear as to the metes and bounds of this term such that the artisan would know how to avoid infringement, i.e. is this a clinical subtype, gene expression subtype, a profile subtype, or otherwise. Applicant is reminded of MPEP 2111.01, section IV: An applicant is entitled to be his or her own lexicographer and may rebut the presumption that claim terms are to be given their ordinary and customary meaning by clearly setting forth a definition of the term that is different from its ordinary and customary meaning(s). See In re Paulsen, 30 F.3d 1475, 1480, 31 USPQ2d 1671, 1674 (Fed. Cir. 1994). The specification does not provide any limiting definition for this term (nor does it define what “PB” means for that matter), but at best teaches [0007] that “patients having a mucosal-like expression profile may be characterized as having a CD-PBmu subtype.” However, examples are not limiting definitions. Clarification is requested via amendment. To advance prosecution and avoid confusion, the examiner suggests amending the claim to recite “CD-PB mucosal (CD-PBmu) subtype” for the very first mention of this term (whereas subsequent mentions can simply be “CD-PBmu subtype”).
Claim 12 recites “detecting…relative to a reference expression profile”. In this case, it is unclear as to the metes and bounds of the “reference expression profile” such that the artisan would know how to avoid infringement. The specification teaches “gene expression from a classified CD-PBT clustered tightly with non-JBD subjects and gene expression drifted from a peripheral toward a mucosal profile, classified as CD-PBmu(cosal).” [0027 and Figure 1B]. However, examples are not limiting definitions and this is not commensurate in scope with what is being claimed. Clarification is requested via amendment.
Claim 14 recites “wherein the at least 10 or more genes comprises…”. However, parent claim 12 already recites “10 or more genes” (that are different from those recited in claim 14). Therefore, it is unclear in what way claim 14 further limits the subject matter of parent claim 12 since it does not seek to add on to or further limit the gene group recited in parent claim 12 (but in fact appears to replace them). Clarification is requested via amendment. In addition, claim 14 is rejected under 35 USC 112 4th paragraph for failing to specify a further limitation of the claimed subject matter. To advance prosecution and avoid confusion, the examiner suggests amending the claim to recite “The method of claim 12, wherein the at least 10 or more genes further comprises….”.
Improper Markush Rejection
Claims 12 and 14 are rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984).
A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
A Markush claim contains an “improper Markush grouping” if:
(1) the species of the Markush group do not share a “single structural similarity,” or (2) the species do not share a common use. Members of a Markush group share a “single structural similarity” when they belong to the same recognized physical or chemical class or to the same art-recognized class. Members of a Markush group share a common use when they are disclosed in the specification or known in the art to be functionally equivalent. See MPEP § 2117.
In this case, the improper Markush grouping is considered to be each of the 10 or more genes listed in claims 12 and 14, respectively. The recited alternative species in the groups set forth here do not share a single structural similarity, as each different gene that could be detected is itself located in a separate region of the genome and has its own structure. The genes recited in the instant claims, do not share a single structural similarity since each consists of a different nucleotide sequences with different expression patterns. The only structural similarity present is that all detected positions are part of nucleic acid molecules. The fact that the markers comprise nucleotides per se does not support a conclusion that they have a common single structural similarity because the structure of comprising a nucleotide alone is not essential to the common activity of being correlated with CD-PBmu. Accordingly, while the different markers are asserted to have the property of being expressed in with CD-PBmu, they do not share a single structural similarity. MPEP 2117 (II)(A) provides the following guidance as to what constitutes a physical, chemical, or art recognized class:
A recognized physical class, a recognized chemical class, or an art-recognized class is a class wherein “there is an expectation from the knowledge in the art that members of the class will behave in the same way in the context of the claimed invention. In other words, each member could be substituted one for the other, with the expectation that the same intended result would be achieved”
The recited genes do not belong to a recognized chemical class because there is no expectation from the knowledge in the art that the genes will behave in the same manner and can be substituted for one another with the same intended result achieved. In other words, there is no expectation from the knowledge in the art that each of the recited genes would function in the same way in the claimed method; it is only in the context of this specification that it was disclosed that all members of this group may behave in the same way in the context of the claimed invention. Further, there is no evidence of record to establish that it is clear from their very nature that each of the recited genes possess the common property of being associated with CD-PBmu. Applicant is encouraged to provide evidence to the contrary. MPEP 2117 (II) further states the following:
Where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the compounds do not appear to be members of a recognized physical or chemical class or members of an art-recognized class, the members are considered to share a "single structural similarity" and common use when the alternatively usable compounds share a substantial structural feature that is essential to a common use. Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984).
The recited alternative species do not share a substantial common structure just because they are all nucleic acids. The sugar phosphate backbone of a nucleic acid chain is not considered to be a substantial common structural feature to the group of genes being claimed because it is shared by ALL nucleic acids. Further, the fact that the genes all have a sugar phosphate backbone does not support a conclusion that they have a common single structural similarity because the structure of comprising a sugar phosphate backbone alone is not essential to the asserted common use of being associated with CD-PBmu.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use. Following this analysis, the claims are rejected as containing an improper Markush grouping.
Conclusion
No claims are allowed.
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