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
The Amendment filed 7/27/2026 in response to Office Action of 4/27/2026, is acknowledged and has been entered. Claims 1-9 and 11-14 are now pending. Claims 1 and 12 are amended. Claim 14 is new.
Prior Rejections: The 112(a) written description rejections cited in previous Office Action dated 4/27/2026 are hereby withdrawn in view of claim amendments to incorporate the sequences of the anti-CD26 antibody. The 112(a) WD regarding claim 8 (deposit) is withdrawn due to amendment to the specification demonstrating public availability of the biological deposit
Claims 1-9 and 11-14 are currently being examined.
New Rejection
(Necessitated by Amendments)
Claim Rejections - 35 USC § 103
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.
Claims 1-6 and 8-14 are rejected under 35 U.S.C. 103 as being unpatentable over Bacigalupo et al (Treatment of Patients with Steroid Refractory Acute Graft Vs Host Disease (SR-GvHD): A Matched Paired Analysis of Anti-CD26 (Begelomab) Compared to Other Treatment; blood, vol 128, dec 2016; pg 671), in view of Clinical Trial NCT02411084 (Version History 1/3/2020) and Francesco et al (US20150017178 A1; Published 1/15/2015).
It is noted that the instant specification discloses that Begelomab is an example of the anti-CD26 antibody encompassed by claim 1
The sequences of begelomab (SEQ ID Nos: 1, 2, 3, 5 7-11;) is disclosed on pages 14-15 of the instant specification, and comparison with sequences demonstrates it includes these CDRs from the claims.
Bacigalupo teaches a method of treating GvHD comprising administering an anti-CD26 monoclonal antibody (begelomab). Bacigalupo teaches that the antibody is administered at dose of 4.5 mg/m2/day for five days, followed by 5 additional biweekly doses for an additional 6 doses. Bacigalupo teaches that there were no adverse events attributable to Begelomab. Bacigalupo teaches that begelomab induced a high remission rate on day 28. [Whole Abstract]
However, Bacigalupo does not teach that the anti-CD26 antibody is administered at a dose range between 8.0 mg/m2/day – 25.0 mg/m2/day every other day for a total of 16 doses.
NCT02411084 teaches a method of treating GvHD comprising administering a CD26 monoclonal antibody, begelomab. NCT02411084 teaches that begelomab has been shown to inhibit immune response and therapeutic improvements. NCT02411084 teaches that begelomab is administered for 5 consecutive days, followed by every 3 days. Regarding claims 4 and 5, NCT02411084 teaches that begelomab is an IgG2b monoclonal antibody. [Whole document]
Francesco teaches a method of treating GvHD comprising administering an anti-CD26 monoclonal antibody, comprising administering the agent for five consecutive days. [Abstract, 0273] Regarding claims 3-5, Francesco teaches that the antibody is a full-length antibody, a monoclonal antibody, and has an isotype selected from IgG2, specifically IgG2b isotype. [0105] Regarding claim 8, Francesco teaches that the anti-CD26 antibody is produced from a hybridoma cell line deposited at CBA-ICLC of Genoa (Italy) as deposit number PD 12002. [0019, 0048-0050] Francesco teaches that the doses of the anti-CD26 antibody can depend on factors, including BSA, age, weight, and purpose of administration. Francesco teaches that for use in the treatment of GvHD a dose of at least 4.5 mg/m2/day, which includes 8 and 10 mg/m2/day can be administered. [0190-0191] Furthermore, Francesco teaches that the pharmaceutical composition for administration to patients comprises the antibody in an amount between 0.1 and 10 mg/m2/day. [0192]
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to treat GvHD comprising administering an anti-CD26 antibody at a dose between 8-25 mg/m2/day for five consecutive days, followed by every other day for 16 doses, at the instantly claimed doses. One would have been motivated to, and have a reasonable expectation of success, because: (1) the prior art demonstrates the use and success of using an anti-CD26 antibody for the treatment of GvHD, (2) the prior art above teaches administering the anti-CD26 antibody for five consecutive days, (3) Bacigalupo and NCT02411084 both teach the use of an anti-CD26 antibody administered for 5 days consecutively, and teach that it’s administered every 3 days afterwards, (4) Bacigalupo teaches that there were no adverse events attributable to Begelomab, and (5) Francesco teaches that for use in the treatment of GvHD a dose of 10 mg/m2/day can be administered.
Bacigalupo recognizes the need in the art to treat GvHD comprising administering an anti-CD26 antibody. Given the recognized need to treat GvHD, the known successes of using this antibody, and known methods of administering an anti-CD26 antibody for five consecutive days at known doses, followed by doses administered after this period, one of skill in the art could have pursued administering an anti-CD26 antibody every other day at dose range between 8-25 mg/m2/day after administering it for five consecutive days in the method Bacigalupo, with a reasonable expectation of success.
Claim(s) 7 is rejected under 35 U.S.C. 103 as being unpatentable over Bacigalupo et al (Treatment of Patients with Steroid Refractory Acute Graft Vs Host Disease (SR-GvHD): A Matched Paired Analysis of Anti-CD26 (Begelomab) Compared to Other Treatment; blood, vol 128, dec 2016; pg 671), Clinical Trial NCT02411084 (Version History 1/3/2020) and Francesco et al (US20150017178 A1; Published 1/15/2015), as applied to claims 1-6 and 8-13, above, and further in view of Trill et al (Production of monoclonal antibodies in COS and CHO cells, Current Opinion in Biotechnology, volume 6, Issue 5, 1995, Pages 553-560).
The teachings of cited art are recited above. However, they do not teach that the anti-CD26 antibody is produced in Chinese hamster ovary (CHO) cells. (claim 7)
Trill teaches the known methods of using of Chinese hamster ovary cells (CHO) for producing monoclonal antibodies. [Whole document]
It is noted that claim(s) 7 require the anti-CD26 antibody is produced in Chinese hamster ovary (CHO) cells. This limitation would have been obvious to those of ordinary skill in the art because: (1) the prior art all teach the method and use of the instantly claimed anti-CD26 antibody, and (2) Trill teaches the known methods of producing antibodies comprising utilizing CHO cells.
Response to Arguments
Applicant amended claim 1 to recite that the antibody concentration ranges from 8.0 mg/m²/day to 25 mg/m²/day. Applicant argues that Bacigalupo's disclosed dose of 4.5 mg/m²/day fall outside of this range and that the disclosed dose is barely over half the dosage of the lowest dose in Applicant's claimed range, and five times lower than the highest claimed dose. The Applicant argues that the other cited sources do not appear to disclose treatment regimens that are any closer to the dose range in amended claim 1. Applicant argues that a person of ordinary skill in the art would not have had a reasonable expectation of success in modifying the disclosed antibody therapy to those with much higher doses, as a person of ordinary skill would expect potential adverse effects from such a dosage increase. Applicant argues that the cited art does not disclose administration schedules that would render the method of claim 1 obvious. Applicant argues that while the total number of doses is the same, the individual doses are even smaller in comparison to those claimed than the dosages in Bacigalupo, and the frequency of maintenance doses in NCT02411084 (every three days) is less than that in claim 1 (every other day). Applicant argues that the combined effect of lower individual dosage and less frequent doses compound the differences in overall dosage between the prior art and the claimed method, making it even less likely that a person of ordinary skill in the art would have a reasonable expectation of success in safely administering the claimed dosage without adverse effects.
Applicants’ arguments have been considered but are not persuasive. The amendments of the claims have been addressed in the above rejection. With regards to the dosing schedule, the Examiner relied on the combination of references to render this obvious. Bacigalupo, NCT02411084 and Francesco all teach that the antibody is administered once daily for five days, followed by additional doses. Bacigalupo teaches that these additional doses were administered biweekly, whereas the clinical trial administered the antibody every 3 days. The Applicant argues that a person of ordinary skill in the art would not have a reasonable expectation of success to safely administer the antibody without adverse effects. However, contrary to Applicant’s arguments, the cited art demonstrates that administration of the antibody did not result in adverse events that were due to the antibody. Thus, since the cited art demonstrates the safety in administering twice a week and every 3 days, one of skill in the art could have pursued administering an anti-CD26 antibody every other day after administering it for five consecutive days in the method Bacigalupo, with a reasonable expectation of success.
Conclusion
THIS ACTION IS MADE FINAL. 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 SARAH A ALSOMAIRY whose telephone number is (571)272-0027. The examiner can normally be reached Monday-Friday 7:30 AM to 5:30 PM.
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/SARAH A ALSOMAIRY/ Examiner, Art Unit 1646
/Zachariah Lucas/ Supervisory Patent Examiner, Art Unit 1600
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