DETAILED ACTION
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 .
Status of Claims
Claims 1, 3, 5-6, 9-11, 19, 21-22, 24-25, 33 and 66 are pending in the instant application. Claims 2, 4, 7-8, 12-18, 20, 23, 26-32, 34-65, 67-70 are cancelled via the amendment filed 12/19/2024.
Priority
This is a 35 U.S.C. 371 National Stage filing of International Application No. PCT/US2022/034757 filed June 23rd, 2022, which claims priority to provisional application No. 63/214,744, filed June 24th, 2021.
Information Disclosure Statement
The Information Disclosure Statement (IDS) filed 02/13/2024 was considered by the Examiner.
Claim Rejections - 35 USC § 103
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 (i.e., changing from AIA to pre-AIA ) 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, 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.
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.
Claim(s) 1, 6, 9-11, 19, 21-22, 24, 33 and 66 is/are rejected under 35 U.S.C. 103 as being unpatentable over Fu et al (WO 2020061103 A1, published March 26th, 2020, as listed on the IDS).
Determining the scope and contents of the prior art. (See MPEP § 2141.01)
Fu teaches a method of treating cancer in a patient which method comprises administering to the patient, in need of such treatment, a therapeutically effective amount of the following compound (claim 46):
PNG
media_image1.png
131
270
media_image1.png
Greyscale
.
This compound is embraced by instant Formula I.
Fu further teaches that the compounds of the disclosure may be used in combination with one or more other drugs in the treatment of disease or conditions for which compounds of this disclosure or the other drugs may have utility (page 100, paragraph 4). Fu teaches that the other drug is a CDK4/6 inhibitor including palbociclib, ribociclib, abemaciclib, and trilaciclib (page 107, paragraph 6).
Ascertainment of the differences between the prior art and the claims. (See MPEP § 2141.02)
Fu does not teach an explicit embodiment where the compound above was administered to a patient with a CDK4/6 inhibitor.
Finding of prima facie obviousness --- rationale and motivation (See MPEP § 2142-2143)
Regarding claim 1, while the prior art does not explicitly teach an embodiment where the compound above with a CDK4/6 inhibitor was administered to a patient, Fu teaches the compounds and their utility in treating cancer. A person having ordinary skill in the art would have been motivated to screen the example compounds of the prior art in the particular utilities to determine which combination would provide optimum treatment outcome.
Regarding claim 6, Fu teaches that the cancer to be treated is colorectal cancer (page 95) and head and neck cancer (page 96).
Regarding claims 9-10, as seen above, Fu teaches the CDK4/6 inhibitor includes palbociclib.
Regarding claims 11 and 24, Fu teaches that a suitable dosage level of the compound of formula I, above, may be about 0.1 to about 500 mg per day (page 97, paragraph 2). This range overlaps with the range as instantly claimed, 50 mg/day to about 500 mg/day. As the ranges overlap the claimed range, a prima facie case of obviousness exists (MPEP § 2144.05).
Regarding claim 19, Fu also teaches that the drugs to be used in combination with the compound above include ALK inhibitors and EGFR inhibitors (page 102).
Regarding claims 21-22, Fu teaches that the preferred manner of administration is oral using a daily dosage regimen (pages 97-98).
Regarding claim 33, Fu also teaches that the drugs to be used in combination with the compound of formula I above includes aromatase inhibitors (page 102).
Regarding claim 66, Fu teaches that the compound of formula I can be administered in combination with an CDK4/6 inhibitor as shown in the rejection of claim 1. While Fu does not specifically teach a kit comprising the compound of formula I and an CDK4/6inhibitor, one of ordinary skill in the art would have a reasonable expectation to make a kit comprising a compound of formula I and an CDK4/6 inhibitor because it is commonly known in the art that compounds are contained in packaging and could be packaged together.
For example, Fu teaches kits (formulations presented in unit-dose or multi-dose containers to be mixed with sterile liquid carrier):
The formulations may be presented in unit-dose or multi-dose containers, for example sealed ampoules and vials, and may be stored in powder form or in a freeze dried (lyophilized) condition requiring only the addition of the sterile liquid carrier, for example, saline or sterile pyrogen-free water, immediately prior to use. Extemporaneous injection solutions and suspensions may be prepared from sterile powders, granules and tablets of the kind previously described.
Fu, Specification, p. 98.
Therefore, claim 66 was prima facie obvious at the time of filing.
Claim 1, 3, 6, 9-11, 19, 21-22, 24, 33 and 66 are rejected under 35 U.S.C. 103 as being unpatentable over Fu et al (WO 2020061103 A1, published March 26th, 2020, as listed on the IDS) as applied to claims 1, 6, 9-11, 19, 21-22, 24, 33 and 66 above, and in further view of Hamilton et al (Cancer Treatment Reviews 45 (2016) 129–138).
The 103 rejection of claims 1, 6, 9-11, 19, 21-22, 24, 33 and 66 over Fu above are incorporated herein by reference.
Determining the scope and contents of the prior art. (See MPEP § 2141.01)
Fu does not explicitly teach that a patient having cancer characterized by a mutation in the CDK 4/6 pathway was selected for treatment. However, as seen in the 103 rejection above, Fu does teach that a CDK 4/6 inhibitor is administered in combination with the compound of formula I to treat head and neck cancer. Fu also teaches the compositions utility in treating cancers with mutations.
Ascertainment of the differences between the prior art and the claims. (See MPEP § 2141.02)
The prior art does not explicitly teach that a patient having cancer characterized by a mutation in the CDK 4/6 pathway was selected for treatment.
Finding of prima facie obviousness --- rationale and motivation (See MPEP § 2142-2143)
However, Hamilton teaches that mutations in the CDK 4/6 is common within cases of head and neck cancers. For instance, Hamilton teaches that amplification of CCND1 is observed in 39% of head and neck cancer cases and loss of p16INK4A in 80% of head and neck cancer cases.
As such, one of ordinary skill in the art would recognize that as Fu teaches a method of treating head and neck cancer, the method would also be treating a patient with a cancer with a mutation in the CDK 4/6 pathway, as Hamilton teaches that a high percentage of head and neck cancer cases have a mutation in the CDK 4/6 pathway.
Further, as seen in the 103 rejection above, Fu teaches that the method of treatment includes the administration of a CDK 4/6 inhibitor and Hamilton teaches that due to the importance of CDK4/6 activity in cancer cells, CDK4/6 inhibitors have emerged as promising candidates for cancer treatment. Also, combination of a CDK4/6 inhibitor with other targeted therapies may help overcome acquired or de novo treatment resistance (abstract).
Claims 1, 5-6, 9-11, 19, 21-22, 24, 33 and 66 is/are rejected under 35 U.S.C. 103 as being unpatentable over Fu et al (WO 2020061103 A1, published March 26th, 2020, as listed on the IDS), as applied to claims 1, 6, 9-11, 19, 21-22, 24, 33 and 66 above, and in further view of Li et al (Int J Clin Exp Pathol 2019;12(3):957-967).
The 103 rejection of claims 1, 6, 9-11, 19, 21-22, 24, 33 and 66 over Fu above are incorporated herein by reference.
Determining the scope and contents of the prior art. (See MPEP § 2141.01)
Fu does not explicitly teach that the patient has cancer characterized by a mutation in KRAS. However, as seen in the 103 rejection above, Fu does teach that a CDK 4/6 inhibitor is administered in combination with the compound of formula I to treat colorectal cancer. Fu also teaches the compositions utility in treating cancers with mutations.
Ascertainment of the differences between the prior art and the claims. (See MPEP § 2141.02)
The prior art does not explicitly teach that a patient having cancer characterized by a mutation in KRAS.
Finding of prima facie obviousness --- rationale and motivation (See MPEP § 2142-2143)
However, Li teaches that 72% of colorectal cancer patients have a mutation in the KRAS. Li further teaches that the G12D mutation made up 47.5% of colorectal cancer patients and the G12V mutation made up 30.6% of colorectal cancer patients.
As such, one of ordinary skill in the art would recognize that as Fu teaches a method of treating colorectal cancer, the method would also be treating a patient with a cancer with a mutation in the KRAS, specifically G12D or G12V, as Li teaches that a high percentage of colorectal cancer cases have a mutation in the G12D or G12 V.
Claim 25 is/are rejected under 35 U.S.C. 103 as being unpatentable over Fu et al (WO 2020061103 A1, published March 26th, 2020, as listed on the IDS) and in further view of Jing Li et al (CLINICAL PHARMACOLOGY & THERAPEUTICS, V.109 N.2, February 2021)
The 103 rejection of claims 1, 6, 9-11, 19, 21-22, 24, 33 and 66 over Fu above are incorporated herein by reference.
Determining the scope and contents of the prior art. (See MPEP § 2141.01)
Fu does not explicitly teach that the compound of Formula I is administered QD or BID for 3 weeks on and 1 week off (28 day schedule). However, as seen in the rejection above, Fu teaches the administration of a compound of Formula I with palbociclib. Fu further teaches that when other drugs are administered with a compound of formula (I), they are administered by a route and in an amount commonly used thereof.
Ascertainment of the differences between the prior art and the claims. (See MPEP § 2141.02)
The prior art does not explicitly teach that the compound of Formula I is administered QD or BID for 3 weeks on and 1 week off (28 day schedule).
Finding of prima facie obviousness --- rationale and motivation (See MPEP § 2142-2143)
However, Jing Li teaches that the standard dosing routine for palbociclib is 125 mg q.d. oral dosing on a 3-weeks-on/1-week-off schedule (page 495, right column, paragraph 6).
Thus, as Fu teaches that the administration regimen is to be based on the common route and amount of the other drug being administered, one of ordinary skill in the art would have been motivated by the teachings of Jing Li to administer the compound of formula I along with palbociclib in the standard dosing regimen as taught by Jing Li.
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.
Claims 1, 3, 5-6, 9-11, 19, 21-22, 24-25, 33 and 66 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 7, 14, 24, 38 and 60 of copending Application No. 18/256, 089 (reference application) in view of Fu et al (WO 2020061103 A1, published March 26th, 2020, as listed on the IDS), Hamilton et al (Cancer Treatment Reviews 45 (2016) 129–138), Li et al (Int J Clin Exp Pathol 2019;12(3):957-967) and Jing Li et al (CLINICAL PHARMACOLOGY & THERAPEUTICS, V.109 N.2, February 2021).
Although the claims at issue are not identical, they are not patentably distinct from each other because:
The copending application claims a method of treating cancer with a compound of instant Formula I and a third MAPK pathway activity inhibitor (claims 1 and 14). Given the teachings of Fu, Hamilton, Li and Jing Li, incorporated herein by reference, the patient populations of the instant application and the specific CDK 4/6 inhibitors are obvious over the claims of the copending application in view of the art.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 3, 5-6, 9-11, 19, 21-22, 24-25, 33 and 66 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 7, 12-14, 20, 32 and 47 of copending Application No. 18/256,091 (reference application) in view of Fu et al (WO 2020061103 A1, published March 26th, 2020, as listed on the IDS), Hamilton et al (Cancer Treatment Reviews 45 (2016) 129–138), Li et al (Int J Clin Exp Pathol 2019;12(3):957-967) and Jing Li et al (CLINICAL PHARMACOLOGY & THERAPEUTICS, V.109 N.2, February 2021).
Although the claims at issue are not identical, they are not patentably distinct from each other because:
The copending application claims a method of treating cancer with a compound of instant Formula I and a third MAPK pathway activity inhibitor (claims 1 and 12). Given the teachings of Fu, Hamilton, Li and Jing Li, incorporated herein by reference, the patient populations of the instant application and the specific CDK 4/6 inhibitors are obvious over the claims of the copending application in view of the art.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 3, 5-6, 9-11, 19, 21-22, 24-25, 33 and 66 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 30, 39, 41-42, 45, 57-63, 65, 85-86, 88-90, 94-95, 107, 112, 127 and 134 of copending Application No. 18/572,404 (reference application) in view of Fu et al (WO 2020061103 A1, published March 26th, 2020, as listed on the IDS), Hamilton et al (Cancer Treatment Reviews 45 (2016) 129–138), Li et al (Int J Clin Exp Pathol 2019;12(3):957-967) and Jing Li et al (CLINICAL PHARMACOLOGY & THERAPEUTICS, V.109 N.2, February 2021).
Although the claims at issue are not identical, they are not patentably distinct from each other because:
The copending application claims a method of treating cancer with a compound of instant Formula I and CDK 4/6 inhibitor (claims3 and 127). Given the teachings of Fu, Hamilton, Li and Jing Li, incorporated herein by reference, the patient populations of the instant application and the specific CDK 4/6 inhibitors are obvious over the claims of the copending application in view of the art.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Anna Grace Kuckla whose telephone number is (703)756-5610. The examiner can normally be reached Monday-Friday 7:30-5.
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) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Clinton A Brooks can be reached at (571)270-7682. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/A.G.K./Examiner, Art Unit 1626
/FEREYDOUN G SAJJADI/Supervisory Patent Examiner, Art Unit 1699