DETAILED OFFICE ACTION
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 amendment filed on 30 December 2025 is acknowledged and entered. Following the amendment, claim 1 is amended.
Currently, claims 1, 3-5, 12-17, 20, 21 and 27 are pending, and claims 1, 5, 21 and 27 are under consideration. Claims 3, 4, 12-17 and 20 remain withdrawn from further consideration as being drawn to a non-elected species.
Prior Art Rejections
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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 of this title, 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 5, 21 and 27 remain rejected under 35 U.S.C. 103 as being unpatentable over
Westhovens et al. (J Rheumatol. 2006 May; 33(5):847-53); CELLTRION, Inc. (“HIGHLIGHTS OF PRESCRIBING INFORMATION” for INFLECTRA (infliximab-dyyb), 4/2016); and Clinical Trial EudraCT Number 2016-002125-11 (8/23/2016, this is the corrected date, i.e., the Date of Competent Authority Decision in section N of the reference (see explanation below)), for the reasons of record set forth in the last Office Action mailed on 7/1/2025, at pages 3-5.
Applicants argument filed on 30 December 2025 has been fully considered, but is not deemed persuasive for the reasons below.
At page 7 of the response, the applicant made similar argument as previously: the deficiencies of Westhovens have been argued many times previously, again, Westhovens discloses a Phase I study to assess the safety, clinical response and pharmacokinetics of SC and IM doses of an experimental formulation of infliximab in patients with rheumatoid arthritis, in contrast, as discussed previously, the claimed invention relates to treatment of inflammatory bowel disease, not RA; Westhovens teaches a dose of only 100 mg every 2 weeks in RA patients, and that intravenous infliximab can be used to treat CD patients; however, it would have been extremely difficult for one of ordinary skill in the art to accurately predict that 120 mg of infliximab administered subcutaneously every 2 weeks in CD; as discussed previously, in Example 3 of the present application, 5 mg/kg intravenous administration of infliximab is compared with 120 mg, 180 mg, and 240 mg of subcutaneous administration; and if the average weight of an adult is assumed to be 60 kg, then infliximab of 5 mg/kg will correspond to the dosage of 300 mg, NOT 120 mg as claimed.
This argument is not persuasive for the reasons of record. Applicants argument is against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). In the instant case, it is the combined teachings of the three cited references, which render the claimed methods obvious. Further, the instant rejection is the obviousness type of rejection under 35 U.S.C. 103; and if Westhovens had taught treating CD (not RA) with infliximab as claimed, the claims would have been rejected under 35 U.S.C. 102 (anticipation). Furthermore, it is unclear as to why it would have been extremely difficult for one of ordinary skill in the art to accurately predict that 120 mg of infliximab administered subcutaneously every 2 weeks in CD, as Westhovens’ Phase I study assessed the pharmacokinetics of SC with 100 mg infliximab, even though it was carried out in RA patients. Furthermore, as discussed previously, Westhovens demonstrated the favorable ACR response in the patients 100 mg SC doses every 2 weeks, which provides guidance for treating other diseases that are indications for using infliximab such as Crohn’s disease (also taught by Westhovens). There is no evidence that Westhovens’ regimen of infliximab 100 mg SC doses every 2 weeks would not be effective for CD; and 120 mg every 2 weeks would be critical for IBD or CD. Furthermore, even if the SC dosage of infliximab for CD may need adjusted, mere optimizing the SC dosage of infliximab for CD based on the teachings of the prior art does not constitute a novel inventive concept, as such would be routine in the art and is well within the purview of a person of ordinary skill in the art. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See also, MPEP 2144.05. II..
At pages 7-8 of the response, the applicant argues that as evidenced by the data, the proportion of patients achieving CDAI-70 or CDAI-100 was higher when infliximab was administered at 120 mg every two weeks than when at 180 mg or 240 mg every 2 weeks (Tables 19 and 20); and the number of patients positive for drug- specific antibodies (AIDA) and neutralizing antibodies (NAb) after 6 weeks of treatment was significantly lower when infliximab was administered at 120 mg (or 240 mg) as a single dose compared to 5 mg/kg (IV) (Table 16 of the specification), while the effect of reducing disease activity was similar or superior (Tables 19 to 21); and that SC 120 mg of infliximab is a significantly lower dose, produces similar or better therapeutic effects, which is an unexpected result which could not have been rendered obvious based on the teachings and suggestions of Westhovens., either alone or in combination with the other two newly cited documents, and certainly would not have been obvious to one of ordinary skill in the art.
This argument is not persuasive for the reasons of record and above. It is unclear what is so “unexpected”, since Westhovens has already demonstrated the favorable treatment response of 100 mg SC doses every 2 weeks over the 3 mg/kg IV regimen in RA patients. As discussed previously, Westhovens teaches that ACR20 was achieved 2 weeks after the last injection by 86.7% of subjects receiving single SC doses, 85.7% receiving SC doses every 2 weeks, 85.7% receiving both IV and SC doses, 57.1% receiving multiple IM doses, and 80.0% receiving SC doses every 4 weeks. Westhovens also teaches that no treatment-related serious adverse events were observed, and there were no serious injection site reactions, and a low-titer infliximab antibody response was detected in 27% of subjects receiving single SC doses, 5% receiving multiple SC doses, and 43% receiving IM doses (abstract, for example). Thus, Westhovens has demonstrated the superiority of SC administration over IM and IV, and that 100 mg SC doses every 2 weeks is a better and effective regimen. Therefore, the argued superiority of SC administration of 120 mg infliximab (vs. IV administration of 5 mg/kg) is not an issue here because such had been demonstrated by the prior art.
At pages 8-9 of the response, the applicant made argument based on the previously filed declaration by Dr. Jean-Frederic Columbel, and argued that the declaration establishes that, in the opinion of Dr. Columbel: (1) The teachings, conclusions and data of Westhovens relate soley to rheumatoid arthritis do not automatically serve as a "guide" for appropriately treating inflammatory bowel disease; and (2) The SC dose of 120 mg of infliximab administered every 2 weeks, as claimed, cannot be considered obvious; and in Crohn's disease and ulcerative colitis, higher doses of infliximab have been consistently required in clinical trials and clinical practice as compared to the doses of infliximab required for treatment of rheumatoid arthritis; thus, one of ordinary skill in the art certainly would not have predicted based upon the disclosure of Westhovens that a lower dose of infliximab (i.e., 120 mg) would be effective in treatment of inflammatory bowel disease (versus rheumatoid arthritis).
This argument is not persuasive for the following reasons: first, the declaration is not based on the instant reference (it is based on the previous rejection), which comprises different/ additional references, and new ground of rejection. Thus, certain arguments are no longer relevant, for example, the reference NCT02883452 is no cited in the instant rejection. Further, with respect to the argument that in Crohn's disease and ulcerative colitis, higher doses of infliximab have been consistently required in clinical trials, applicant is reminded that the requirements for patentability differ from that for FDA approval, which requires clinical trials, while such is not required for patentability.
At page 9 of the response, the applicant argues that CELLTRION discloses the intravenous use of INFLECTRA (a biosimilar), in contrast, the claimed invention recites the subcutaneous administration of infliximab; that (again), while CELLTRION describes IV administration at a dose of 5 mg/kg for IBD, when this dose is converted for use in an adult weighing 60 kg, the total dose utilized is approximately 300 mg, not 120 mg as claimed; and that as above, based upon the experiments and results set forth in the specification, the lower dose of 120 mg achieves superior efficacy as compared to higher doses, which result is completely unexpected.
This argument is not persuasive for the reasons of record and above.
At pages 9-10 of the response, the applicant argues that Clinical Trial EudraCT Number 2016-002125-11 discloses the date cited by the Examiner (i.e., July 1, 2016) is the "[d]ate on which this record was first entered in the EudraCT database", which is not the date that the information contained therein was first disclosed to the public and thus publicly available; that the examiner is requested to provide the exact date the disclosure of the document was made publicly available.
This argument is not persuasive for the following reasons: while applicant is correct as to that the date on which this record was first entered in the EudraCT database is not the public date, the public date of this reference has been corrected to 8/23/2016 (from 7/1/2016) upon further search and investigation. This date is located in the “N” section of the reference provided (9th page). For reference support, see, for example, the following is the result of a Google search:
Google Search result (1/6/2026): when first entered information in eudract is public access - Google Search
AI Overview:
Information entered into EudraCT becomes publicly accessible (via the EU Clinical Trials Register) automatically once a trial is approved by the relevant National Competent Authority (NCA) and Ethics Committee, with protocol details released by default unless commercially confidential, while results are released after the sponsor submits them post-trial, though now largely transitioned to the new CTIS system.
Protocol Information (Pre-CTIS Era)
Immediate Publication: Once a trial was approved by the NCA and Ethics Committee, the protocol-related details (like objectives, design, countries, etc.) were made public in the European Clinical Trials Register (EU CTR).
Confidentiality: Sponsors could request certain data to be kept confidential if it was commercially sensitive, but the default was public access.
Transition to CTIS (Clinical Trials Information System)
New System: As of January 31, 2025, most new EU/EEA trials use the CTIS under Regulation (EU) 536/2014, replacing EudraCT for new applications.
CTIS Transparency: CTIS also has public access by default, with exceptions for personal data, commercially confidential info, etc..
In essence: EudraCT's goal was transparency, making trial details public upon authorization and results public upon submission, a principle largely continued in the new CTIS system.
In addition, “EudraCT & EU CTR Frequently asked questions” (4/16/2021) by EUROPEAN MEDICINES AGENCY discloses that what is the "Date on which this record was first entered in the EudraCT database? This is the date when the National Competent Authority uploaded the CTA in the system. This is not the date of the authorisation. The date of authorisation is visible in Section N when you search for a trial and click on the country code and go to the detailed view of the trial in the EU CT (page 8, item 10.).
At page 10 of the response, the applicant repeatedly argues that Clinical Trial EudraCT Number 2016-002125-11 relates to the treatment of RA not IBD as claimed; that as firmly established by the previously filed Expert Declaration of Dr. Colombel (as described above), the treatment of RA does not serve as a guide to treating IBD.
This argument is not persuasive for the reasons of record and above.
Conclusion:
No claim is allowed.
Advisory Information:
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 extension fee 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 should be directed to Examiner DONG JIANG whose telephone number is 571-272-0872. The examiner can normally be reached on Monday - Friday from 9:30 AM to 7:00 PM. If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Vanessa 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.
/DONG JIANG/
Primary Examiner, Art Unit 1646
1/8/26