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
Information Disclosure
The information disclosure statements submitted 03/27/2025 and 07/10/2025 have been considered.
Response to Amendments
The amendments made to the claims 07/10/2025 have been entered.
Election/Restrictions
In view of the amendments made to the claims, search and examination has bene broaden to include irinotecan.
Status of Claims
Claims 1-24 are currently pending.
Claims 3 and 13 are withdrawn.
Claims 1-2, 4-12, and 14-24 are under examination.
Withdrawn Rejections
In view of the amendments made to the claims, the 102 rejection made in the previous office action has been withdrawn. Elements of the 102 rejection have been include in the now modified 103 rejection below.
Maintained Rejections
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 1-2, 4-12, and 14-24 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ganloev (WO2019/135157) in view of Kawai (BMC Cancer, 2021, 21:116, published online 02/04/2021), Wiseman (Drugs, 1996, Vol. 52(4): 606-623), and Taieb (British Journal of Cancer, 2019, 121:434-442).
In regards to claim 1, 6-7, and 9, Ganloev on p. 4-5 para. [0011] teaches a method of treating patients diagnosed with colorectal cancer or metastatic colorectal cancers comprising administering bevacizumab followed by administering (b) a dose of 85 mg/m2 oxaliplatin, (c) followed by administering a 400 mg/m2 dose of 5-fluorouracil (5-FU), (d) followed by administering a dose of 60 mg/m2 of 6R-MTHF, (e) followed by administering a dose of 2,400 mg/m2 of 5-FU, and (f) followed by administering a dose of 60 mg/m2 of 6R-MTHF. Ganloev in the same paragraph discloses the method further comprising administering bevacizumab at a dose of 5 mg/kg.
In regards to claims 1 and 2, Ganloev on p. 27-28, para. [0086] teaches a treating a patient with stage IV metastatic colorectal cancer, wherein the patient has been diagnosed with metastatic colorectal colon cancer confirmed by sigmoidectomy.
In regards to claim 4-5, Ganloev on p. 6, para. [0017] contemplates repeating steps every two weeks.
In regards to claim 8, the instant claims differs from the art in the timing of administering bevacizumab. The art teaches administration as the first step (see rejection of claim 9 above). Claim 8 specifies administration after administering oxaliplatin. This difference does not seem to amount to a significant change considering that the outcomes of both methods are similar (See rejection of claims 16 and 17 below). It would be within the skillset of one of ordinary skill in the art to alter the methods in Ganloev so that bevacizumab is administer prior to oxaliplatin.
The MPEP section 2144.05 states
“The adjustment of particular conventional working conditions (e.g., determining result effective amounts of the ingredients beneficially taught by the cited references), is deemed merely a matter of judicious selection and routine optimization which is well within the purview of the skilled artisan. Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical.
“[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). Accordingly, this type of modification would have been well within the purview of the skilled artisan and no more than an effort to optimize results.”
In regards to claims 10-12, Ganloev on p. 18, para. [0051]-[0052] contemplates reconstituting 6-MTHF in aqueous media and from a hemisulfate salt.
In regards to claim 14, Ganloev on p. 18, para. [0050] contemplates addition of citric acid and/or ascorbic acid.
In regards to claim 15, Ganloev on p. 19, para. [0053] discusses diastereomeric purity.
In regards to claims 16-17, Ganloev on p. 8, para. [0024] contemplates results of practicing its method which include “no progression of said solid tumors after 2, 4, 8, 16, or 24 weeks of treatment...”.
In regards to claims 18-23, Ganloev on p. 5-6, para. [0012]-[0015] discusses administration times.
Ganloev discusses irinotecan on p. 1, l. 27-29 where it states “Standard first-line systemic therapy for metastatic colorectal cancer, in accordance with current European Society for Medical Oncology (ESMO) guidelines is chemotherapy with 5-Fu, LV, oxaliplatin/irinotecan and bevacizumab.” This is further affirmed by Kawai.
Kawai in its abstract states “Irinotecan (IRI) and oxaliplatin (Ox) are standard therapeutic agents of the first-line treatments for metastatic colorectal cancer (mCRC).
Ganloev does not explicitly discuss continuous intravenous infusion of irinotecan. This is addressed by Wiseman.
Wiseman in sec. Clinical Efficacy teaches continuous intravenous infusion of irinotecan. Additionally, Wisemen teaches doses of irinotecan ranging from 30mg/m2/day by continuous intravenous infusion for 5 days and dose amounts of 200 mg/m administered once every 3 to 4 weeks.
None of Ganloev, Kawai, or Wisemen discuss BRAF-mutant metastatic colon cancer. This is addressed by the teachings of Taieb.
In regards to claim 24, Taieb discusses treatment options for BRAF-mutant metastatic colon cancer. Taieb on p. 437, sec. Current Systemic Treatments for BRAF-MT-MCRC states A more aggressive strategy, involving combination of doublet with EGFR inhibitor, cetuximab, or triplet with bevacizumab, which inhibits vascular endothelial growth factor (VEGF) might be of interest in [metastatic colorectal cancer] patients with BRAF-mt tumours, as suggested by some clinical data, although these data are based on small subgroups.”
Ganloev continues “In a 2010 study by Masi et al., patients with wild-type and mutated BRAF CRC tumours had similar median PFS and OS when the treatment was based on the triplet FOLFOCIRI (folinic acid, fluorouracil, oxaliplatin and irinotecan) with bevacizumab, suggesting that this aggressive therapeutic strategy could also lead to the loss of the negative prognostic impact of BRAF mutation.”
Taieb essentially teaches that combination therapy comprising oxaliplatin and additional chemotherapeutic agents, including 5-FU (fluorouracil) shows promising results in treating metastatic colorectal cancer.
Ganloev teaches a method of treating metastatic colorectal cancer comprising administering oxaliplatin, 5-FU, 6R-MTHF, and further comprising bevacizumab Ganloev additionally teaches it’s method is effective in treating metastatic colorectal cancer. Kawai teaches that standard procedure for treating colorectal cancer and/or metastatic colorectal cancer includes administration of either oxaliplatin or irinotecan. This teaching establishes irinotecan as an alternative to oxaliplatin. Wiseman teaches continuous intravenous infusion of irinotecan. Taieb teaches the efficacy of similar treatments in treating BRAF-mutant metastatic colorectal cancer.
Therefore, it would have been prima facie obvious at the time of the effective filing date for one of ordinary skill in the art to apply the method of Ganloev towards treating BRAF-mutant metastatic colorectal cancer with a reasonable assumption of success.
One of ordinary skill in the art would find motivation to apply the method as Taieb states triplet chemotherapy methods have found success in treating BRAF-mutant metastatic colorectal cancer.
Double Patenting
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.
Co-pending Application 18/075,391
Claims 1-2, 4-12, and 14-24 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 17-21, 32-36, 40, 46-49, 51-54, and 68-74 of copending Application No. 18/075,391 (reference application) in view of Kawai (BMC Cancer, 2021, 21:116, published online 02/04/2021), and Wiseman (Drugs, 1996, Vol. 52(4): 606-623). Although the claims at issue are not identical, they are not patentably distinct from each other because the reference application is drawn to methods of treating colorectal cancer or metastatic colorectal cancer comprising steps similar if not identical to those instantly claimed.
The reference claims are drawn to methods of treating patients diagnosed with colorectal cancer or metastatic colorectal cancer comprising the steps of administering bevacizumab, oxaliplatin, 5-FU, and 6R-MTHF in particular order.
The instant claims are identical except they claim continuous intravenous infusion of irinotecan in place of oxaliplatin. This difference is addressed by Kawai and Wiseman, as discussed in the 103 rejection above.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Applicant in their arguments states that Ganloev does not teach continuous intravenous infusion of a composition comprising 180 mg/m2 of irinotecan. Similar arguments are made in regards to the double patenting rejection.
Applicant states “Ganloev does not teach or suggest the specifically defined dose of a continuous intravenous (IV) infusion of a pharmaceutical composition comprising 180 mg/m2 (of BSA) irinotecan as required by the amended claims. This is repeated in the section regarding the double patenting rejection.
These arguments are addressed by the modifications made to the rejections above. Kawai teaches that irinotecan is also standard first line treatment for metastatic colorectal cancer. Wiseman additionally teaches continuous intravenous infusion of irinotecan.
The 103 rejection and the double patenting rejection are maintained.
New Double Patenting Rejections
U.S. Patent 10,292,984
Claims 1 and 16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 10,292,984 in view of Wiseman (cited above).
The reference claims are drawn to methods comprising steps of administering 5-FU and 6R-MTHF. The steps involved administering 5-FU first, followed 6R-MTH. The method optionally includes administering irinotecan in no specific order. The reference specification in col. 5, Table 1, teaches dose amounts of irinotecan at 180 mg/m2. The reference specification in col. 4 l. 15-16 also teaches that doses of 6R-MTHF can be repeated. While the reference specification does not teach repeated steps of 5-FU, it would be obvious to one of ordinary skill in the art to repeat said step of administering the 5-FU in view of the teaching that 6R-MTHF may be repeated. The reference claims also claim 6R-MTHF dose amounts of 60 mg/m2. Where the reference claims are drawn to 500 mg/m2 of 5-FU, it would be within the skillset of one ordinary skill to modify the claim to instead use 400 mg/m2. Reference claims 3 and 6 are drawn to embodiments wherein the human subject suffers from colorectal cancer.
Wiseman teaches continuous intravenous administration of irinotecan.
U.S. Patent 10,328,079
Claims 1 and 16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-23 of U.S. Patent No. 10,328,079 in view of Wiseman (cited above).
The reference claims are drawn to methods comprising administering 10-1000 mg/m2 of 5-FU, 5-1000 mg/m2 of 6R-MTHF, administering a second dose of 5-FU, and optionally administering a final dose of 5-1000 mg/m2 of 6R-MTHF. Reference claim 2 specifies the methods involved administering to a human diagnosed with colorectal cancer or metastatic colorectal cancer. Reference claim 6 claims additionally administering the anticancer drug irinotecan.
Wiseman discusses dose of irinotecan. The reference specification in col. 17/18 Table 1 teaches irinotecan dose amounts of 180 mg/m2. Wiseman teaches continuous intravenous administration of irinotecan.
U.S. Patent 10,639,311
Claims 1 and 16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 10,639,311 in view of Wiseman (cited above).
The reference claims are drawn to a method comprising administering 400 mg/m2 of 5-FU followed by 60-240 mg/m2 of 6R-MTHF, followed by 2400 mg/m2 of 5-FU. Reference claim 5 further comprises administering irinotecan. The reference specification in col. 4, l. 19-20 teaches doses of 6R-MTHF can be repeated. The reference specification in col. 6, table 1 teaches doses of irinotecan at 180 mg/m2. Reference claim 4 specifies that the human subject suffers from colorectal cancer.
Wiseman teaches continuous intravenous administration of irinotecan.
U.S. Patent 11,389,452
Claims 1 and 16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-41 of U.S. Patent No. 11,389,452 in view of Wiseman.
The reference claims are drawn to methods comprising administering 400 or 500 mg/m2 of 5-FU and 30-240 mg/m2 of 6R-MTHF to a subject suffering from colorectal cancer. Reference claim 6 specifies a method further comprising administering irinotecan. The reference specification in col. 4 l. 16-17 teaches that doses of 6R-MTHF can be repeated. One of ordinary skill in the art would find it obvious to also repeat doses of 5-FU in view of the teaching that doses may be repeated. The reference specification in col. 5, Table 1 teaches irinotecan doses of 180 mg/m2. Wiseman teaches continuous intravenous administration of irinotecan.
Conclusion
No claims allowed.
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/L.G./Examiner, Art Unit 1624
/SUSANNA MOORE/Primary Examiner, Art Unit 1624