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 election without traverse of group I and the species rs229527 and inhibitor of TL1A in the reply filed on 2/3/26 is acknowledged.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-4, 9, 12-14, and 51-59 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites a method of treating CD in a subject comprising administering an anti-TL1A antibody, “provided that” rs229527 is detected.
Recitation of “provided that rs229527 is detected” does not impart a clear method step. The metes and bounds of “provided that” are not definite and it is unclear whether the method requires a step of detecting rs229527. Claim 2 requires that rs229527 is detected, but it is unclear whether this occurred in the past tense or is required as an active method step.
Claim 4 recites “based on” monitoring expression levels of one or more genes. The specific metes and bounds for the criteria of being “based on” are not clear. The claim does not recite a clear step of increasing the dosage upon a specific expression requirement of a specific gene.
Claim 12 recites “based at least in part”, which is not definite language. The specific metes and bounds for being based at least in part on rs229527 being detected is not clear.
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, 9, 12-15, and 51-59 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 specification discloses that a CD patient is characterized as having or not having a mucosal-like CD expression signature (CD-PBmu) by detecting one or more polymorphisms that is predictive of a transcriptomic profile for the CD-PBmu subtype. Therefore, a CD patient may or may not have a CD-PBmu according to the specification and the specification does not adequately describe the specific genus of polymorphisms that are predictive of any transcriptomic profile for the CD-PBmu subtype. Without further description, recitation of “CD-PBmu” would not allow one to readily envision which genes or polymorphisms are necessarily included or excluded from the genus.
The specification discloses that: [0052] Patients having the one or more polymorphisms associated with the CD-PBmu subtype may be suitable for subtype-specific treatment, including administration with a therapeutic agent that targets a biomolecule provided in Table 1A, Table 1B, Table 20 or Table 3, or a biomolecule in a biological pathway of a biomolecule provided in Table 1A, Table 1B, Table 20 or Table 3. In some embodiments, the subtype-specific treatment comprises a therapeutic of Table 18B and/or a kinase modulator of a kinase in Table 18A. In some embodiments, the subtype-specific treatment comprises a modulator of microRNA 155 (miR-155). The specification does not describe the specific parameters required for the recited CD-PBmu.
Claim 4 requires monitoring expression levels of one or more genes associated with the CD-PBmu subtype. The specification does not adequately describe which genes are associated in any manner to any CD-PBmu subtype. Without further description of the structure required for the function, one would not be able to readily envision which genes have any possible association to any possible CD-PBmu subtype.
Claim 51 requires detection of one or more genes of a transcriptomic signature, but the specification does not adequately describe which specific genes have which specific signature required for the confirmation of what specific CD-PBmu subtype. Without further description of the genus, one would not be able to recognize which genes are required to have what level of expression to identify what subtype to be treated.
Claim 53 requires that the subtype is characterized by any mucosal-like transciptomic signature. The specification does not adequately describe how the subtype is “characterized” by the presence of any possible mucosal-like transciptomic signature.
Claim 55 requires for the subtype to be “associated” with perianal disease and/or fistula, etc. The specification does not adequately describe which subtypes have any possible association to each of the recited species of claim 55.
The MPEP states that for a generic claim, the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. See MPEP § 2163. If the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. See MPEP § 2163. Although the MPEP does not define what constitute a sufficient number of representative species, the courts have indicated what do not constitute a representative number of species to adequately describe a broad genus. In Gostelli, the courts determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gostelli, 872, F.2d at 1012, 10 USPQ2d at 1618. Additionally, in Carnegie Mellon University v. Hoffman-La Roche Inc., Nos. 07-1266, -1267 (Fed. Cir. Sept. 8, 2008), the Federal Circuit affirmed that a claim to a genus described in functional terms was not supported by the specification’s disclosure of species that were not representative of the entire genus. Furthermore, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents of the University of California v. Eli Lilly & Co. the court stated:
"A written description of an invention involving a chemical genus, like a description of a chemical species, 'requires a precise definition, such as by structure, formula, [or] chemical name,' of the claimed subject matter sufficient to distinguish it from other materials." Fiers, 984 F.2d at 1171, 25 USPQ2d 1601; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284985 (CCPA 1973) ("In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus ...") Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The Guidelines for Examination of Patent Applications under the 35 USC § 112, first paragraph, “Written Description” Requirement”, published at Federal Register, Vol. 66, No. 4, pp. 1099-1111 outline the method of analysis of claims to determine whether adequate written description is present. The first step is to determine what the claim as a whole covers, i.e., discussion of the full scope of the claim. Second, the application should be fully reviewed to understand how applicant provides support for the claimed invention including each element and/or step, i.e., compare the scope of the claim with the scope of the description. Third, determine whether the applicant was in possession of the claimed invention as a whole at the time of filing.
Thus, having analyzed the claims with regard to the Written Description guidelines, it is clear that the specification does not disclose a representative number of species for agents within the instant enormous genus that function as claimed. Thus, one skilled in the art would be led to conclude that Applicant was not in possession of the claimed invention at the time the application was filed.
Claims 1-4, 9, 12-15, and 51-59 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of detecting rs229527 and correlating to CD-PBmu subtype of Crohn’s disease, does not reasonably provide enablement for a method of treating any Crohn’s disease via delivery via any means of an anti-TL1A antibody. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
Factors to be considered in a determination of lack of enablement include, but are not limited to:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)
The claims are directed to a method of treating any Crohn’s disease, not necessarily subtype CD-PBmu, via delivery of an anti-TL1A antibody after detection of rs229527.
The specification does not demonstrate that detection of rs229527 alone necessarily correlates to the presence of Crohn’s disease in an otherwise undiagnosed person, but rather demonstrates that the presence of rs229527 in an individual with Crohn’s disease indicates that the individual has the CD-PBmu subtype of Crohn’s. The method recites detection of rs229527, which appears to be for stratifying a type of Crohn’s disease in a patient with Crohn’s disease but treatment of any Crohn’s disease.
Therefore, the method would treat this subtype rather than any Crohn’s disease. From a review of the prior art, it appears that delivery of an anti-TL1A antibody would treat Crohn’s disease. Therefore, the claims appear to be directed to a known method of treating Crohn’s disease via delivery of an anti-TL1A antibody (Takedatsu et al. (GASTROENTEROLOGY Vol. 135, No. 2, 2008, 552-567) “provided that” rs229527 is detected, which would indicate that the patient has the CD-PBmu subtype and therefore this is the subtype that is being treated. It appears that the “provided that” language of the claims intends to require detection of rs229527 as a step before the method of treatment and therefore the method treats the subtype.
The specification demonstrates stratifying Crohn’s patients into CD-PBmu vs CD-PBT subtypes based upon transcriptomic profiling, but does not demonstrate that rs229527 is detected in any type of Crohn’s disease.
Amendment of the claims to be directed to a method of detecting rs229527 in a subject with Crohn’s disease and correlating the presence of rs229527 with the CD-PBmu subtype of Crohn’s disease, followed by treating the subtype with an anti-TL1A antibody would overcome this rejection, for example.
Additionally, there is no guidance in the specification as filed that teaches how to deliver any anti-TL1A antibody via any means and predictably outcome of treating any Crohn’s disease wherein rs229527 has been detected in vivo.
For example, Chen et al. (Theranostics 2022, Vol. 12, Issue 8, 3719-3746) teach that antibodies have challenges in crossing various complex biological barriers in the body. Firstly, as a kind of protein, these antibodies are susceptible to enzymatic and chemical constituents in the physiological environment. Some antibody fragments are also rapidly metabolized in the body. Secondly, antibodies often cause off-target cytotoxicity and adverse events, such as cytokine release syndrome (CRS) and organ toxicity. Some adverse reactions even endanger patients’ lives, limiting the comprehensive application of antibody therapy to a certain extent. (page 3720) Chen et al. teach that antibodies are tolerated on different levels depending on the mode of delivery (pages 3730-3731).
The specification is not enabling for delivery via any means (i.e. oral) of an anti-TL1A antibody and the predictable treatment of any Crohn’s disease. The scope of the claims in view of the specification as filed together do not reconcile the unpredictability in the art to enable one of skill in the art to make and/or use the claimed invention, namely a broad method of treating any Crohn’s disease after detection of rs229527 via delivering an anti-TL1A antibody via any mode of administration encompassing in vivo effects.
MPEP 2164.01
Any analysis of whether a particular claim is supported by the disclosure in an application requires a determination of whether that disclosure, when filed, contained sufficient information regarding the subject matter of the claims as to enable one skilled in the pertinent art to make and use the claimed invention.
Also, MPEP 2164.01(a)
A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557,1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).
Given the teachings of the specification as discussed above, one skilled in the art could not predict a priori whether introduction of an anti-TL1A antibody in vivo by the broadly disclosed methodologies of the instantly claimed invention, would result in successful treatment of any Crohn’s disease after detection of rs229527 in vivo.
To practice the claimed invention, one of skill in the art would have to de novo determine; the stability of the molecule in vivo, delivery of the molecule to the whole organism, specificity to the target tissue in vivo, dosage and toxicity in vivo, and entry of the molecule into the cell in vivo and the effective action therein. Without further guidance, one of skill in the art would have to practice a substantial amount of trial and error experimentation, an amount considered undue and not routine, to practice the instantly claimed invention.
A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation (see MPEP 2164.01(a)).
Claim Rejections - 35 USC § 103
It is noted that the rejection has been withdrawn because there is no motivation or prior teaching in the art for the detection of rs229527 and the treatment of Crohn’s Disease.
Conclusion
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 nonprovisional extension fee (37 CFR 1.17(a)) 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 mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Amy R Hudson whose telephone number is (571)272-0755. The examiner can normally be reached M-F 8:00am-6:00pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Neil Hammell can be reached at 571-270-5919. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/AMY ROSE HUDSON/Primary Examiner, Art Unit 1636
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