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 .
DETAILED ACTION
Response to Amendment
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 allowance or after an Office action under Ex Parte Quayle, 25 USPQ 74, 453 O.G. 213 (Comm'r Pat. 1935). 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, prosecution in this application has been reopened pursuant to 37 CFR 1.114.
The Information Disclosure Statement (IDS) filed 6 February 2026 has been entered. Applicant’s amendment of the claims filed 3 February 2026 has been entered. Applicant’s remarks filed 3 February 2026 are acknowledged.
Claims 1-16, 19-20, 23, 25-30 and 33 are cancelled. Claims 34-48 have been added. Claims 17-18, 21-22, 24, 31-32 and 34-48 are pending and under examination.
New Grounds of Objections/Rejections
Claim Objections
Claim 35, 39-40 and 45-46 are objected to because of the following informalities:
In claim 35, the phrase in the last line, “is used in the detecting step”, should be deleted.
Claims 39 and 45 use an acronym without defining what it represents at the first use of the acronym (see for example, “JAK”). While the claims can reference acronyms, the material presented by the acronym must be clearly set forth at the first use of the acronym.
In claims 40 and 46, the term “anti-TNFa agent” should be “an anti-TNFa agent”.
Appropriate correction is required.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 17-18, 21-22, 24, 31-32, 34-36, 42 and 48 are rejected under 35 U.S.C. 101 because the claimed invention is not directed to patent eligible subject matter.
The 2019 Revised Patent Subject Matter Eligibility Guidance (published in the Federal Register (84 FR 50) on January 7, 2019) articulates the following steps to evaluate subject matter eligibility:
Step-1: Are the claims directed to a process, machine, manufacture or composition of matter?
The claims are directed to a process, and Step-1 is YES.
Step 2A-Prong One (2A-1): Are the claims directed to a judicially recognized exception?
Independent claim 17 recites:
“A method for diagnosing and treating ulcerative colitis or primary sclerosing cholangitis complicated with ulcerative colitis in a subject, the method comprising:
obtaining a blood sample from the subject;
detecting the presence or absence of an antibody that immunologically reacts with integrin aVb6 in the blood sample by contacting the blood sample with a full-length integrin aVb6 or a fragment thereof and detecting binding between the full-length integrin aVb6 or a fragment thereof and the antibody;
diagnosing the subject as having ulcerative colitis or primary sclerosing cholangitis complicated with ulcerative colitis when the presence of the antibody is detected; and
administering an amount of a therapeutic agent effective for treating ulcerative colitis or primary sclerosing cholangitis complicated with ulcerative colitis to the diagnosed subject;
wherein the therapeutic agent is an immunomodulator selected from an antibody and a small molecule drug.”
Independent claim 21 recites:
“A method for diagnosing and treating ulcerative colitis or primary sclerosing cholangitis in a subject, the method comprising:
obtaining a blood sample from the subject;
contacting the blood sample with a solid-phase support comprising an antigen immobilized thereon, the antigen being a full-length integrin aVb6 or a fragment thereof;
detecting the binding of the antigen to an antibody that immunologically reacts with integrin aVb6, thereby detecting the presence or absence of the antibody in the blood sample;
diagnosing the subject as having ulcerative colitis or primary sclerosing cholangitis when the presence of the antibody is detected; and
administering an amount of a therapeutic agent effective for treating ulcerative colitis or primary sclerosing cholangitis to the diagnosed subject;
wherein the therapeutic agent is an immunomodulator selected from an antibody and a small molecule drug.”
The claims recite the correlation between the presence of an antibody that immunologically reacts with integrin aVb6 in a blood sample of a subject and ulcerative colitis or primary sclerosing cholangitis. This type of correlation is a consequence of natural process, i.e., a law of nature, which belongs to a judicial exception. The claims recite a judicial exception, therefore, Step 2A-Prong One is Yes.
Step 2A-Prong Two (2A-2): Is the judicial exception integrated into a practical application?
The 2019 PEG defines the phrase “integration into a practical application” to require an additional element or a combination of additional elements in the claim to apply, rely on, or use the judicial exception. The claims do not recite additional element(s) demonstrating that the claims as a whole integrate the exception into a practical application. “One way to demonstrate such integration is when the additional elements apply or use the recited judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition. The application or use of the judicial exception in this manner meaningfully limits the claim by going beyond generally linking the use of the judicial exception to a particular technological environment, and thus transforms a claim into patent-eligible subject matter. Such claims are eligible at Step 2A, because they are not "directed to" the recited judicial exception.” See MPEP 2106.04(d)(2). Further, “The treatment or prophylaxis limitation must be "particular," i.e., specifically identified so that it does not encompass all applications of the judicial exception(s).” (ibid.) In the instant case, the treatment limitation is not "particular". The claims recite “administering an amount of a therapeutic agent effective for treating ulcerative colitis or primary sclerosing cholangitis complicated with ulcerative colitis to the diagnosed subject; wherein the therapeutic agent is an immunomodulator selected from an antibody and a small molecule drug”, however, the claims do not specify what these antibodies or small molecules are, and the claims merely instruct a doctor to generically “treat it”. The totality of these steps (without a particular treatment) does not integrate the exception into a practical application. Therefore, Step 2A-Prong Two is No.
Step-2B: If the claims are directed to a judicial exception and do not integrate the judicial exception, do the claims provide an inventive concept?
The courts have recognized determining the level of a biomarker in blood by any means as well-understood, routine, conventional activity in the life science arts when they are claimed in a merely generic manner (e.g., at a high level of generality) or as insignificant extra-solution activity. Mayo, 566 U.S. at 79, 101 USPQ2d at 1968; Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1362, 123 USPQ2d 1081, 1088 (Fed. Cir. 2017). See MPEP 2106.05(d) II. In the instant case, determining the present of an antibody that immunologically reacts with integrin aVb6 in a patient’s blood sample by using an assay, such as ELISA, would be well-understood, routine and conventional to one skilled in the art. A skilled artisan would readily know to use an assay as recited in the instant claims to determine the presence or absence of an antibody that immunologically reacts with integrin aVb6 in a patient’s blood sample. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception, and Step-2B is NO.
Based upon an analysis with respect to the claims as a whole, the claims are determined to be directed to a law of nature without significantly more. Accordingly, the instant claims are not patent-eligible.
Claim Rejections - 35 USC § 112
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 17-18, 21-22, 24, 31-32, 34-36, 42 and 48 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 claims contain 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.
Independent claims 17 and 21 have been amended to recite “administering an amount of a therapeutic agent effective for treating ulcerative colitis or primary sclerosing cholangitis … to the diagnosed subject; wherein the therapeutic agent is an immunomodulator selected from an antibody and a small molecule drug”. The claims are broad and encompass the use of a genus of antibodies and small molecules. However, the specification fails to provide adequate written description and evidence of possession of these molecules that are “immunomodulators” and “effective for treating ulcerative colitis or primary sclerosing cholangitis”. What Applicant has described in the specification are antibodies directed against TNFa, including infliximab, adalimumab, golimumab, and vedolizumab, and small molecules which include a steroid drug, a JAK inhibitor, 5-aminosalicyclic acid, azathioprine, mercaptopurine, tacrolimus, ciclosporin, and tofacitinib. The specification describes that these therapeutic agents are effective for treating a patient diagnosed as having ulcerative colitis or primary sclerosing cholangitis based on the presence of anti-integrin avb6 autoantibodies detected in a blood sample of the patient. Except for the therapeutic agents, i.e., the antibodies and small molecules set forth above, there is no adequate written description in the specification for the broad genus of antibodies and small molecules that can act as an immunomodulator and are effective for treating ulcerative colitis or primary sclerosing cholangitis. The specification does not teach the structural characteristics of the genus, nor provides sufficient teachings regarding the correlation of structure to function. The claims, as written, even encompass those not yet identified at the time of the invention. For example, Bassarab et al. (U.S. Patent No. 11,897,964 B2, Date of Patent: Feb. 13, 2024) discloses a newly identified antibody that specifically binds to human PSGL-1 and that can be used for treating ulcerative colitis. Leshchiner et al. (US 2020/0268736 A1, Pub. Date: Aug. 27, 2020) discloses small molecule compounds having the activity of modulating CARD9 and useful for treating ulcerative colitis. Clearly, there is no evidence that Applicant was in possession of the claimed genus.
To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making of the claimed product, or any combination thereof. In this case, there is no sufficient teachings regarding the structural characteristics of the genus, nor the correlation of structure to function. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states that “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” (See page 1117.) 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). As discussed above, the skilled artisan cannot envision the detailed structures of the encompassed genus of molecules, and therefore, conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that is part of the invention and reference to a method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483. In Fiddes, claims directed to mammalian FGF’s were found to be unpatentable due to lack of written description for that broad class. The specification provided only the bovine sequence.
Therefore, only the antibodies directed against TNFa, including infliximab, adalimumab, golimumab, and vedolizumab, and the small molecules of a steroid drug, a JAK inhibitor, 5-aminosalicyclic acid, azathioprine, mercaptopurine, tacrolimus, ciclosporin, and tofacitinib, but not the full scope of the claimed therapeutic agents, are adequately described in the disclosure.
Claims 17-18, 21-22, 24, 31-32, 34-36, 42 and 48 are further 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 for diagnosing and treating ulcerative colitis or primary sclerosing cholangitis in a subject, comprising, inter alia, administering an amount of a therapeutic agent effective for treating ulcerative colitis or primary sclerosing cholangitis, wherein the therapeutic agent is an immunomodulator selected from an anti-TNFa agent, a steroid drug, a JAK inhibitor, 5-aminosalicyclic acid, azathioprine, mercaptopurine, tacrolimus, ciclosporin, and tofacitinib, does not reasonably provide enablement for using the broad genus of antibodies and small molecules that act as an immunomodulator. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
As set forth above, the claims encompass the use of a broad genus of therapeutic agents that are immunomodulators, specifically, antibodies and small molecule drugs. The specification, however, fails to teach sufficient structural characteristics of these molecules, and there is no sufficient teaching regarding the correlation of structure to function. In the absence of the guidance from the specification, a skilled artisan cannot envision the detailed structures of these molecules, therefore, would not know how to make these molecules.
Further, regarding an immunosuppressant and/or anti-inflammatory drug, the specification does not show evidence that any immunosuppressant or anti-inflammatory drug can be used to a patient with ulcerative colitis or primary sclerosing cholangitis. Philpott et al (Postgrad. Med. J., 2014, Vol. 90:411–419) teaches that NSAIDs (anti-inflammatory drugs) can cause, precipitate or perpetuate ulcerative colitis (p. 414, col. 2, section “Drug-induced IBD). Yang et al. (Clin. J. Gastroenterol., 2023, Vol. 17(1):65–68) that leflunomide (an immunosuppressant) can induce collagenous colitis. These effects would contradict their use for treating a patient with ulcerative colitis. Therefore, the scope of patent protection sought by Applicant as defined by the claims fails to correlate reasonably with the scope of enabling disclosure set forth in the specification.
Clearly, the instant specification does not enable one of skill in the art to use the broad genus of molecules to treat a patient with ulcerative colitis or primary sclerosing cholangitis. See In re Wands', 858 F.2d at 737, 8 USPQ2d at 1404. The test of enablement is not whether any experimentation is necessary, but whether, if experimentation is necessary, it is undue. The factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is "undue" include, but are not limited to: (1) the breadth of the claims; (2) the nature of the invention; (3) the state of the prior art; (4) the level of one of ordinary skill; (5) the level of predictability in the art; (6) the amount of direction provided by the inventor; (7) the existence of working examples; and (8) the quantity of experimentation needed to make or use the invention based on the content of the disclosure.
Given the breadth of the claims, in light of the predictability of the art as determined by the number of working examples, the level of skill of the artisan, and the guidance provided in the instant specification and the prior art of record, it would require undue experimentation for one of ordinary skill in the art to make and use the claimed invention.
Allowable Subject Matter
Claims 37-41 and 43-47 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
CLAIMS 37-41 AND 43-47 ARE OBJECTED.
CLAIMS 17-18, 21-22, 24, 31-32, 34-36, 42 AND 48 ARE REJECTED.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Xiaozhen Xie, whose telephone number is 571-272-5569. The examiner can normally be reached on M-F, 8:30-5.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Vanessa L. Ford, can be reached on 571-272-0857. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/XIAOZHEN XIE/Primary Examiner, Art Unit 1674
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