DETAILED ACTION
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2 Applicant's amendment, filed on 08/11/2025, is acknowledged.
3. Claims 1-5, 7-8, 10-14, 17-20, 24-37 are pending.
4. Upon reconsideration the Examiner has extended the search to cover a human patient who has perianal fistulizing moderately to severely active Crohn’s disease and had a lack of an adequate response with, lost response to, or was intolerant to treatment with an immunomodulator and/or a corticosteroid. Accordingly, Applicant traversal is moot.
4. Applicant’s election with traverse the species of (i) a human patient who has perianal fistulizing moderately to severely active Crohn’s disease and had a lack of an adequate response with, lost response to, or was intolerant to treatment with an immunomodulator and/or a corticosteroid (ii) and measuring a PDAI score, filed on 08/11/2025, is acknowledged.
5. Claims 3-5, 13-14, 18-20, 22, 24, 27-28, 32, 36 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected inventions.
6. Claims 1, 2,7-8, 10-12, 16-17, 25-26, 29-31, 33-35, 37 are under examination as they read on the species of (i) a human patient who has perianal fistulizing moderately to severely active Crohn’s disease and had a lack of an adequate response with, lost response to, or was intolerant to treatment with an immunomodulator and/or a corticosteroid (ii) and measuring a PDAI score.
7. Applicant’s IDS, filed 8/11/2025, is acknowledged.
8. The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
9. Claims 1, 2,7-8, and 34 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Sandborn et al (N Engl J Med, Aug. 2013;369:711-21, IDS#10-11).
Sandborn-2013 et al teach that in an integrated study with separate induction and maintenance trials, Sandborn et al assessed intravenous vedolizumab therapy (300 mg) (comprising claimed SEQ ID NOs: 1-9) in adults with active Crohn’s disease. In the induction trial, 368 patients were randomly assigned to receive vedolizumab or placebo at weeks 0 and 2 (cohort 1), and 747 patients received open-label vedolizumab at weeks 0 and 2 (cohort 2); disease status was assessed at week 6. In the maintenance trial, 461 patients who had had a response to vedolizumab were randomly assigned to receive placebo or vedolizumab every 8 or 4 weeks until week 52 (i.e., 0, 2, 6, 10, 14, 18 . . . wks or 0, 2, 6, 14, 22, . . . wks from the initial dose, up to 52 wks) (abstract). Among patients in cohorts 1 and 2 who had a response to induction therapy, 39.0% and 36.4% of those assigned to vedolizumab every 8 weeks and every 4 weeks, respectively, were in clinical remission at week 52 (as measured by clinical remission (i.e., had a score on the Crohn’s Disease Activity Index [CDAI]), as compared with 21.6% assigned to placebo (P<0.001 and P = 0.004 for the two vedolizumab groups, respectively, vs. placebo). Sandborn concluded that vedolizumab-treated patients with active Crohn’s disease were more likely than patients receiving placebo to have a remission, but not a CDAI-100 response, at week 6; patients with a response to induction therapy who continued to receive vedolizumab (rather than switching to placebo) were more likely to be in remission at week 52. Adverse events were more common with vedolizumab (see abstract). Sandborn et al teach that among the eligible patients are those who had had no response to or had had unacceptable side effects from one or more of the following: glucocorticoids, immunosuppressive agents (i.e., azathioprine, mercaptopurine, or methotrexate), or TNF antagonists (page 712, under Patients). Antibiotics treatment was permitted (page 712, right col., 1st ¶ under Patients).
Sandborn-2013 et al teach that study visits were scheduled at weeks 0, 2, 4, and 6 in the trial of induction therapy and every 4 weeks thereafter during the trial of maintenance therapy until week 52. Adverse events, CDAI score, neurologic symptoms of PML as assessed by means of questionnaires (see the Supplementary Appendix), the use of concomitant medications, and the presence or absence of fistulae were evaluated at all visits.
Table 1. Demographic and Baseline Clinical Characteristics and History of Crohn’s Disease Medication among Patients in the Induction Trial.
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191
1377
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140
1381
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Sandborn teaches that information regarding draining fistulae (manifest as anal fistula) is shown in Figure S6 in the Supplementary Appendix. Table S4 shows:
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272
1461
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379
1460
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Fig. S6 illustrates the maintenance trial: closure of draining fistulae in patients with draining fistulae at baseline.
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458
851
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Regarding the “at least 50% of the perianal draining fistulae are closed 30 weeks after the initial dose”, the prior art teaches the same method of treating the same target population with the same antibody regimen, the claimed results of at least 50% of perianal draining fistulae are closed would be inherent.
Claim 7 is included because although Sandborn et al is silent with regard "100% of the draining perianal fistula are closed by the treatment" per se; the method, the product used in the reference method are the same as the claimed method. Therefore “100% of the draining perianal fistula are closed by the treatment” is considered inherent properties.
The reference teachings anticipate the claimed invention.
10. The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
11. Claims 1, 2,7-8, 10-12, 16-17, 25-26, 29-31, 33-35, 37 are rejected under 35 U.S.C. 103 as being unpatentable over Sandborn et al (N Engl J Med, Aug. 2013;369:711-21, IDS), in view of the Sandborn et al (GASTROENTEROLOGY 2002;122:512–530, IDS#26).
The teachings of Sandborn-2013 have been discussed, supra.
The reference teachings differ from the instant claims only in the recitation that the treatment is further measured by a Perianal Disease Activity Index (PDAI) scope of the human patient, and wherein the PDAI score of patients is reduced by at least 3 points from baseline in claims 11, 30, 31.
Sandborn-2002 et al described an instrument to measure the severity of perianal Crohn’s disease called the Perianal Disease Activity Index (PDAI) (Table 3) and its validation in patients undergoing treatment with metronidazole. The PDAI incorporates 5 items: discharge, pain, restriction of sexual activity, type of perianal disease, and degree of induration. Each category is graded on a 5-point Likert scale ranging from no symptoms (score of 0) to severe symptoms (score of 4). A higher score indicates more severe disease. The PDAI has been used as a secondary endpoint in a placebo-controlled trial of infliximab for the closure of perianal fistulas. It is likely that the PDAI will become the perianal Crohn’s disease equivalent of the CDAI. The authors recommend that the fistula drainage assessment be used to measure fistula closure in patients whose symptoms are predominantly because of actively draining enterocutaneous or perianal fistulas. However, once additional prospective trials have been performed with the PDAI score as a secondary endpoint, and the minimum clinically significant difference in the PDAI and the cut-off value indicating remission have been determined, the PDAI may become the preferred instrument to measure the disease activity of perianal fistulas. Table 12 shows that the endpoint decrease in PDAI ≥ 2
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to measure the severity of perianal Crohn’s disease using PDAI score and its validation in patients undergoing treatment with vedolizumab for the closure of perianal fistulas because PDAI is equivalent of the CDAI and because PDAI is the preferred instrument to measure the disease activity of perianal fistulas.
From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
12. Claims 1, 2,7-8, 10-12, 16-17, 25-26, 29-31, 33-35, 37 are rejected under 35 U.S.C. 103 as being unpatentable over Sandborn et al (N Engl J Med, Aug. 2013;369:711-21, IDS), in view of the WO/2012/151247/US 12286479 and Sandborn et al (GASTROENTEROLOGY 2002;122:512–530, IDS).
The teachings of Sandborn-2013 and Sandborn-2002 references have been discussed, supra.
The reference teachings differ from the instant claims only in the recitation that of a fourth and subsequent doses of 108 mg of the humanized antibody by subcutaneous administration every 2, 3 or four weeks after the third subsequent dose in claim 25.
US 12286479 claims priority to WO/2012/151247, their teachings are identical. The teachings of the `479 is used in the rejection.
The `479 claims methods for treating inflammatory bowel disease (IBD) in a human patient in need thereof, the method comprising intravenously administering an initial dose of 300 mg of a humanized antibody having binding specificity for human α4β7 integrin to the human patient, intravenously administering a second dose of 300 mg of the humanized antibody to the human patient 2 weeks after the initial dose, intravenously administering a third dose of 300 mg of the humanized antibody to the human patient 6 weeks after the initial dose, and subcutaneously administering a dose of 108 mg of the humanized antibody to the human patient via a prefilled syringe or an autoinjector every two weeks starting at 14 weeks after the initial dose, wherein the IBD is ulcerative colitis or Crohn's disease, wherein the treated human patient is in clinical remission, and wherein the humanized antibody is an IgG1 isotype and comprises the following CDRs: Light chain: CDR1 SEQ ID NO: 11 CDR2 SEQ ID NO: 12 CDR3 SEQ ID NO: 13 Heavy chain: CDR1 SEQ ID NO: 8 CDR2 SEQ ID NO: 9 CDR3 SEQ ID NO: 10 (see issued claim 12), wherein the antibody is vedolizumab (see issued claim 16), wherein the treated human patient having ulcerative colitis has mucosal healing (see issued claim 18), the Crohn's disease is moderately to severely active Crohn's disease (see issued claim 20), wherein the human patient has Crohn's disease and has a clinical response for at least 6 months or at least 9 months (see issued claims 26-27), wherein the treated human patient reduces or discontinues use of corticosteroids (see issued claim 30).
Those of skilled in the art would have had a reason to adapt the dosing regimen taught by the `479 patent in treatment of human patient suffering from perianal fistulizing Crohn’s disease taught by Sandborn-2013 et al because the efficacy of the subcutaneous vedolizumab 108 mg every 2 weeks following IV doses of 300 mg of VDZ at weeks 0, 2 and 6 achieved clinical response.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to measure the severity of perianal Crohn’s disease using PDAI score and its validation in patients undergoing treatment with vedolizumab for the closure of perianal fistulas because PDAI is equivalent of the CDAI and because PDAI is the preferred instrument to measure the disease activity of perianal fistulas.
From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
13. The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
14. Claims 1, 2,7-8, 10-12, 16-17, 25-26, 29-31, 33-35, 37 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11884731.
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the `731 patent are directed to methods for treating a human patient suffering from perianal fistulizing Crohn's disease, the method comprising identifying a human patient having fistulizing moderately to severely active Crohn's disease and who had a lack of an adequate response with, loss response to, or was intolerant to treatment with a tumor necrosis factor-alpha antagonist and has at least one perianal draining fistula(e), administering a humanized antibody having binding specificity for human α4β7 integrin to the human patient, wherein the humanized antibody is administered to the human patient according to the following dosing regimen: a. an initial dose of 300 mg of the humanized antibody as an intravenous infusion; b. followed by a second subsequent dose of 300 mg of the humanized antibody as an intravenous infusion at about two weeks after the initial dose; c. followed by a third subsequent dose of 300 mg of the humanized antibody as an intravenous infusion at about six weeks after the initial dose; d. followed by a fourth and subsequent doses of 300 mg of the humanized antibody as an intravenous infusion every eight weeks after the third subsequent dose of the humanized antibody as needed; and e. administering antibiotics during weeks 0 to 6 of treatment with the humanized antibody; wherein at least 50% of the perianal draining fistulae are closed 30 weeks after the initial dose; wherein the Perianal Disease Activity Index (PDAI) score of the patient is reduced by at least 3 points from baseline; and wherein the humanized antibody comprises an antigen binding region of nonhuman origin and at least a portion of an antibody of human origin, wherein the humanized antibody has binding specificity for the α4β7 complex, wherein the antigen-binding region comprises the CDRs: Light chain: CDR1 SEQ ID NO:7 CDR2 SEQ ID NO:8 and CDR3 SEQ ID NO:9; and Heavy chain: CDR1 SEQ ID NO:4 CDR2 SEQ ID NO:5 and CDR3 SEQ ID NO:6, wherein said human patient further has an abdominal fistula(e), an enterocutaneous fistula(e), or a combination thereof, wherein perianal fistula(e) closure is measured by magnetic resonance imaging (MRI) assessment, wherein 100% of the draining perianal fistula(e) are closed by the treatment, wherein the patient further had a lack of an adequate response with, loss response to, or was intolerant to treatment with an azathioprine, 6-mercaptopurine, or methotrexate, wherein the human patient further had a lack of an adequate response with or loss of response to a corticosteroid, wherein the humanized antibody is vedolizumab. The claims of the `731 anticipate the instant claims.
With respect to claim 25 and dependent claims thereof, the specification of the `731 teaches the use of vedolizumab subcutaneously at 108 mg at two, three or four weeks intervals after the use of VDZ intravenous infusion 300 mg at zero, two, and six weeks, which renders the instant claims obvious.
15. No claim is allowed.
16. Any inquiry concerning this communication or earlier communications from the examiner should be directed to MAHER M HADDAD whose telephone number is (571)272-0845. The examiner can normally be reached on Monday-Friday from7:00AM to 4:30PM. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu, can be reached at telephone number 571-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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October 23, 2025
/MAHER M HADDAD/ Primary Examiner, Art Unit 1644