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 07/22/2026, is acknowledged.
3. Claims 1, 4, 6, 10, 18, 19, 25, 28, 29, 32, 33, and 35-57 are pending.
4. Upon Applicant argument, the Examiner has extended the search to cover the species of both with and without antibiotic.
5. Applicant’s election without traverse the species of (i) intravenous administration, a 300 mg dose, and administration at 0, 2, and 6 weeks and every 4/8 weeks thereafter, (ii) a patient who has a modified Pouchitis Disease Activity Index (mPDAI) of 5 or greater and has a minimum endoscopic subscore of 2 at selection, had undergone proctocolectomy and ileal pouch anal anastomosis (IPAA) for ulcerative colitis, (iii) with/out antibiotic and (iv) a patient who had undergone proctocolectomy and IPAA for ulcerative colitis (UC), filed on 07/22/2026, is acknowledged.
6. Claims 1, 4, 6, 10, 18, 19, 25, 28, 29, 32, 33, and 35-57 are under examination as they read on method of treating chronic pouchitis in a human subject has a modified Pouchitis Disease Activity Index (mPDAI) of 5 or greater at selection, and had undergone proctocolectomy and ileal pouch anal anastomosis (IPAA) for ulcerative colitis (UC) comprising (i) intravenous administration of a 300 mg dose of vedolizumab at 0, 2, and 6 weeks and every 4/8 weeks thereafter vedolizumab, (ii) a patient who has a modified Pouchitis Disease Activity Index (mPDAI) of 5 or greater and has a minimum endoscopic subscore of 2 at selection, had undergone proctocolectomy and ileal pouch anal anastomosis (IPAA) for ulcerative colitis, (iii) with/out antibiotic and (iv) a patient who had undergone proctocolectomy and IPAA for ulcerative colitis (UC).
7. Applicant’s IDS, filed 07/22/2026, 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.
9. Claims 1, 4, 6, 10, 18, 19, 25, 28, 29, 32, 33, and 35-57 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by ClinicalTrails (NCT02790138, 5/31/2016, IDS).
NCT02790138 teaches the efficacy and safety of vedolizumab (comprising the claimed SEQ ID NOs) intravenous (IV) in participants with a proctocolectomy and ileal pouch anal anastomosis (IPAA) for ulcerative colitis (UC) who have developed chronic or recurrent pouchitis, or require continuous antibiotic treatment (see Brief Summary). The NCT`138 teaches that the efficacy and safety of 300 mg IV vedolizumab in the treatment of chronic pouchitis within 1 year of screening visit or requiring continuous antibiotics. The patient will receive vedolizumab 300 mg IV at Weeks 0, 2, 6, 14, 22, and 30 alone with concomitant antibiotic treatment with ciprofloxacin 500 mg twice daily through Week 4 (see Detailed Descripton). The NCT`138 teaches that total screening patients using PDAI endoscopic score wherein total score ranges 0 to 6, wherein maximum score indicates worsening of the disease. The Clinicaltrial teaches that inclusion of patients who has a history of ileal pouch anal anastomosis (IPAA) for ulcerative colitis (UC) completed at least 1 year prior to the Screen Visit, mPDAI ≥ 5. Patients (human) has a history of ileal pouch anal anastomosis (IPAA) for ulcerative colitis (UC) completed at least 1 year prior to the Screening Visit (criteria #4). Patient has pouchitis that is chronic or recurrent, defined by a modified Pouchitis Disease Activity Index (mPDAI) ≥5 and >2 episodes within 1 year of the Screening Visit or requiring long-term continuous low-dose antibiotic therapy taken daily on an ongoing basis (eg, ciprofloxacin 250-500 mg/day or metronidazole 500 mg/day taken for several weeks or months at a time) or frequent pulse antibiotic therapy (Criteria #5). Patient agrees to stop antibiotic therapy on Day 1 of the study and switch to ciprofloxacin through Week 4 of study ( Criteria #6). The overall time to participate in this study is 34 weeks (see Detailed Description).
Claims 28-29, 32, 37-39, 45-47 are included because while the prior art teachings may be silent as to the claimed outcome results of the claimed method; the method, the product used in the reference method are the same as the claimed method. The Courts have held that there is no requirement that those of ordinary skill in the art know of the inherent property. See MPEP 2131.01(d) and MPEP 2112 - 2113. It is noted that the CAFC recently held in Bristol-Myers Squibb Co. v. Ben Venue Laboratories Inc., 58 USPQ2d 1508 (CA FC 2001) that when a claimed process is not directed to a new use, consists of the same steps described in a prior art reference, and the newly discovered results of the known process directed to the same purpose are inherent, the process is not patentable.
“It is a general rule that merely discovering and claiming a new benefit of an old process cannot render the process again patentable.” In re Woodruff, 919 F.2d 1575, 1578 (Fed. Cir. 1990). When “a claimed new benefit or characteristic of an invention otherwise in the prior art” is an inherent property of the old invention, “the new realization alone does not render the old invention patentable.” Perricone v. Medicis Pharm. Corp., 432 F.3d 1368, 1377 (Fed. Cir. 2005).
The functions recited in the wherein clause flow naturally from the teachings of the prior art. Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985 (“The fact that appellant has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious.”), and Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347 (Fed. Cir. 1999) (“[T]he discovery of... a scientific explanation for the prior art's functioning, does not render the old composition patentably new to the discoverer.”)). Here, the recited functional outcome “ the human subject achieves remission of pouchitis”, “remission is defined as pouchitis having a modified Pouchitis Disease Activity Index (mPDAI) of <5 and a reduction in overall mPDAI score of ≥ 2 from baseline“, “remission is achieved by about 14 weeks following the initial dose of the anti-α4β7 antibody, or antigen binding fragment thereof “ would naturally and necessarily flow from inhibition of α4ß7 by administering Vedolizumab. Accordingly, the prior art teaches the same method, the product used in the reference method are the same as the claimed method. Therefore, the claimed functional outcome would naturally and necessarily flow from inhibition of α4ß7 with the Vedolizumab in treating chronic pouchitis patient has a mPDAI of 5 or greater, a minimum endoscopic subscore of 2 and IPAA for UC.
The reference teachings anticipate the claimed invention.
10. Claims 1, 4, 6, 10, 18, 19, 25, 28, 29, 32, 33, and 35-57 are rejected under 35 U.S.C. 103 as being unpatentable over Bethge et al. (BMJ Open Gastro Feb. 2017;4: e000127, IDS #5) or Mangla et al. (American Journal of Gastroenterology, (October 2016); 111(1):S824‐S825, Abstract #: 1729), each in view of ClinicalTrils (NCT02790138, 5/31/2016, IDS #2).
Bethge et al reported a case of a successful combination therapy of vedolizumab (VDZ) (comprising the claimed SEQ ID NOs) and ETA in a patient with ulcerative colitis with pouchitis and SPA. A 41-year-old patient underwent proctocolectomy with IPAA as a result of refractory pancolitis. Thereafter, he developed severe chronic refractory pouchitis. Subsequently various combinations of antibiotics, mesalazine, steroids and probiotics were administered with only transient response. Owing to increased joint pain and ongoing pouch inflammation treatment with a TNF-inhibitor adalimumab was initiated 3 years after surgery. Owing to persistent pouchitis (chronic) and a severe impact on his quality of life, inhibition of α4/β7-integrin was initiated with the therapeutic antibody vedolizumab (VDZ) at standard dose (300 mg at 0, 2 and 6 weeks) and anti-TNF therapy was stopped. The application intervals were continued every 8 weeks. After 6 weeks of therapy with VDZ, the clinical symptoms of pouchitis disappeared, but SpA substantially worsened with clinical enthesiopathy, peripheral arthritis, significant vertebral pain, further stiffening, a rise in C reactive protein and a BASDAI-Index of 24. Therapy with TNF-inhibitor etanercept (ETA) (50 mg/week) was started in addition to VDZ. After 20 weeks of VDZ endoscopic and histopathological assessment of the pouch revealed normal, uninflamed mucosa (figure 1). After 10 months of treatment the patient is still without any symptoms of pouchitis or joint pain. No side effects of the combination of α4/β7-integrin and TNF-inhibition were seen (Case Report, 2nd & 3d ¶, Fig. 1). Bethge teaches that VDZ was highly effective for the long lasting, refractory pouchitis. VDZ seems to be effective for maintaining remission as well. Especially for patients who suffer from chronic antibiotic refractory pouchitis and show a loss of response this seems to be an alternative therapeutic option. (Discussion, 3rd ¶). Fig. 1 shows that (A) refractory pouchitis with a PDAI of 10, (B) pouch with normal mucosa and PDAI of 4 in week 20 after VDZ; (C) histological aspect of chronic refractory pouchitis, (D) histological aspect of uninflamed pouch mucosa after therapy. PDAI, Pouchitis Disease Activity Index; VDZ, vedolizumab.
Mangla et al teach that restorative proctocolectomy with ileal‐pouch anal anastomosis (IPAA) is the surgical treatment of choice in patients with ulcerative colitis. Pouchitis is the most common complication after IPAA and its treatment has not been standardized. Vedolizumab has been used in the treatment of ulcerative colitis but its use in inflammatory conditions of the pouch has not been evaluated. Retrospective chart review was performed on patients with IPAA and pouchitis in our institution who had been exposed to vedolizumab. Pouchitis was confirmed by evaluation of clinical, endoscopic, and laboratory parameters. We identified 4 patients with ulcerative colitis who underwent restorative proctocolectomy with IPAA and were exposed to vedolizumab after IPAA. A Caucasian male with IPAA and pouch repair/reconstruction and a history of chronic untreated pouchitis developed moderate pouchitis mainly affecting the proximal pouch, refractory to antibiotics, adalimumab and infliximab. He achieved complete mucosal healing one month after four vedolizumab infusions (See Figures). A Caucasian male with recurrent pouchitis refractory to steroids, antibiotics, adalimumab and certolizumab pegol developed prepouch ileitis and pouch inflammation suggestive of Crohn's disease (CD) that responded to three vedolizumab infusions along with antibiotics with mucosal healing after one month. A Caucasian female intolerant to infliximab and adalimumab developed CD of the pouch requiring diverting loop ileostomy due to anal pain. Seven months later she developed pouchitis that responded to three vedolizumab infusions and steroids with repeat pouchoscopy after two weeks revealing scant/rare pouch ulcerations and anal‐ IPAA stricture. A Hispanic female developed proximal pouch and pouch inlet inflammation and cuffitis refractory to antibiotics and adalimumab. She received five vedolizumab infusions, and methotrexate was initiated four weeks after the first vedolizumab infusion. She did not respond to vedolizumab and repeat pouchoscopy one week after the last infusion revealed deep pouch ulcerations and cuffitis. ESR and CRP decreased after treatment in 3 out of 4 patients (See Table). Vedolizumab was successful in the treatment of inflammatory conditions of the pouch in three out of four IPAA patients. Inflammatory markers improved in three out of four patients. Further studies are needed to examine its potential role for treating refractory pouchitis.
The reference teachings differ from the claimed invention only in the recitation that that the administration is intravenously in claim 32; further comprising administering an antibiotic, wherein the antibiotic is discontinued by 4 weeks following the initial administration of the anti-α4β7 antibody in claim 19, wherein the antibiotic is ciprofloxacin in claim 36, 43, 52.
The teachings of the ClinicalTrils (NCT02790138 has been discussed, supra.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to administer the VDZ antibody intravenously as taught by the NCT`138, and further administer an antibiotic such as ciprofloxacin together with the VDZ and discontinue the antibiotic treatment after 4 weeks in the treatment of chronic pouchitis taught by Bethge et al and Mangla et al reafferences because "[I]t is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456 (CCPA 1955); see also In re Peterson, 315 F.3d 1325 (Fed. Cir. 2003). "Only if the 'results of optimizing a variable' are 'unexpectedly good' can a patent be obtained for the claimed critical range." In re Geisler, 116 F.3d 1465, 1469 (Fed. Cir. 1997) (quoting In re Antonie, 559 F.2d 618, 620 (CCPA 1977)). "[D]iscovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." In re Boesch, 617 F.2d 272, 276 (CCPA 1980).
It is obvious to continue treatment with antibiotic along with the anti-α4β7 antibody in the chronic pouchitis treatment and to eliminate the antibiotic after one month after the initial anti-α4β7 antibody treatment since VDZ alone was effective to treat chronic pouchitis as taught by Bethge and Mangla et al references.
From the reference teachings, 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.
11. 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.
12. Claims 1, 4, 6, 10, 18, 19, 25, 28, 29, 32, 33, and 35-57 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 7, 11, 14-15, 33, 38-39 and 41-43 of copending Application No. 17655541 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the `541 application claims methods of treating chronic pouchitis in a human subject, said method comprising selecting a human subject having chronic pouchitis, wherein the human subject has a modified Pouchitis Disease Activity Index (PDAI) of 5 or greater, has a minimum endoscopic subscore of 2, and has a proctocolectomy and ileal pouch anal anastomosis (IPAA) for ulcerative colitis (UC), and intravenously administering a therapeutically effective dose of 300 mg of a humanized anti-α4β7 antibody, or antigen binding fragment thereof, to the subject at weeks 0 and 2, and administering ciprofloxacin to the human subject, wherein ciprofloxacin is discontinued by 4 weeks following the initial administration of the humanized anti-α4β7 antibody, or antigen binding fragment thereof, such that chronic pouchitis is treated, wherein the humanized antibody, or antigen binding fragment thereof, comprises a heavy chain variable region comprising a CDR3 domain as set forth in SEQ ID NO: 4, a CDR2 domain as set forth in SEQ ID NO: 3, and a CDR1 domain as set forth in SEQ ID NO: 2; and comprises a light chain variable region comprising a CDR3 domain as set forth in SEQ ID NO: 8, a CDR2 domain as set forth in SEQ ID NO: 7, and a CDR1 domain as set forth in SEQ ID NO: 6,wherein the human subject achieves remission of pouchitis by about 14 weeks following the initial dose of the humanized antibody, wherein remission is defined as pouchitis having a modified Pouchitis Disease Activity Index (mPDAI) of <5 and a reduction in overall mPDAI score of >2 from baseline, wherein the antibody, or antigen binding fragment thereof, comprises a heavy chain variable region as set forth in SEQ ID NO: 1 and a light chain variable region as set forth in SEQ ID NO: 5.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
11. No claim is allowed.
12. The art made of record and not relied upon is considered pertinent to applicant's disclosure:
(i) Schmid et al. Successful treatment of pouchitis with Vedolizumab, but not fecal microbiota transfer (FMT), after proctocolectomy in ulcerative colitis. Int J Colorectal Dis (2017) 32:597–598, published online: Jan 17, 2017, IDS #7.
Schmid et al teach a successful treatment of pouchitis with 300 mg i.v. at weeks 0, 2, 6, and every 8 weeks Vedolizumab (comprising the claimed SEQ ID NO) after proctocolectomy with IPAA in ulcerative colitis in a human patient. After five doses, pouch and ileal ulcerations had healed completely (apart from one fourth of the circumference of the afferent limb entry), the stenosis was easily traversable, and edema and mucous exudates were no longer present. Schmid et al found good clinical and endoscopic response encouraging further investigations on clinical response and mucosal healing. Clinically, the patient is now in excellent condition, reports about ten daily stools without any abdominal discomfort (see the entire document).
(ii) Philpott et al. Efficacy of Vedolizumab in Patients with Antibiotic and Anti-tumor Necrosis Alpha (TNFa) Refractory Pouchitis. Inflammatory bowel diseases, (1 January 2017) Vol. 23, No. 1, pp. E5-E6, IDS #4.
Philpott et al present 4 cases of patients with refractory pouchitis who after 3 months of open-label vedolizumab therapy were noted to have improved symptoms and measurable improvement in the endoscopic appearance of the pouch. They speculate that the gut-specific immune modulation mediated by vedolizumab results in these notable responses to therapy. This warrants further study to validate the use of this medication in antibiotic and anti-tumor necrosis factor a refractory pouchitis, along with better understanding of the mechanism of this form of pouch dysfunction.
(iii) Bo et al. Efficacy of Vedolizumab in Patients with Antibiotic and Anti-tumor Necrosis Alpha Refractory Pouchitis. Inflammatory Bowel Diseases, Volume 23, Issue suppl_1, February 2017, Page S14, https://doi.org/10.1097/01.MIB.0000512551.05295.7f.
Bo et al teach that refractory pouchitis is a risk factor for pouch failure and surgical excision. While TNFα inhibitors have been reported to be effective as treatment for pouchitis there is no data regarding the use of vedolizumab in refractory pouchitis. In this study we evaluated the clinical and endoscopic response to vedolizumab in refractory pouchitis. Bo et al teach that three patients were identified as having refractory pouchitis with loss or lack of response to antibiotics, corticosteroids, and at least one TNFα inhibitor along with a variety of other modalities of therapy. Each patient underwent pouch endoscopy before initiation of vedolizumab and repeat endoscopy within 4 months of initiation of treatment. Vedolizumab was administered as per standard dosing regimen. The Pouch Disease Activity Index (PDAI) endoscopic subscore was evaluated by the 2 investigators independently and reported as an average. The clinical record was reviewed to determine patient reported response to therapy. Pouch endoscopy 4 months after initiation of vedolizumab which revealed improved mucosa of the pouch with PDAI score of 1. She noted improvement in symptoms of diarrhea. All 3 patients had improved endoscopic scores and reported clinical improvement in terms of diarrhea and pain. Bo et al conclude that vedolizumab in open label use for chronic antibiotic- and anti-TNFα refractory, chronic pouchitis demonstrated improvement in both symptoms and endoscopy scores.
(iv) Jamot, S., Won the Battle, Lost the War: Crohn’s Flare After Fecal Microbiota Transplant (FMT) for Recurrent C. difficile Infection. American Journal of Gastroenterology, (October 2016) Vol. 111, Supp. Supplement 1, pp. S833-S834. Abstract Number: 1744.
Jamot presents the case of a 36-year-old man with complicated past GI history since diagnosis of UC at age seven with colectomy and J-pouch formation by age nine. Recurrent episodes of pouchitis post-surgery and ulcers in the pouch and of the ileum above the pouch led to an eventual diagnosis of Crohn’s disease of the pouch. The patient was treated with infliximab with improvement in symptoms but no significant improvement on endoscopy. Treatment was switched to vedolizumab with good clinic (see abstract).
13. 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.
Information regarding the status of an application may be obtained from Patent Center. Status information for published applications may be obtained from Patent Center. Status information for unpublished applications is available through Patent Center for authorized users only. Should you have questions about access to Patent Center, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) Form at https://www.uspto.gov/patents/uspto-automated- interview-request-air-form.
August 23, 2026 /MAHER M HADDAD/ Primary Examiner, Art Unit 1644
Prosecution Insights