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
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Claims 1-32, and 52 have an effective filing date of 09 OCT 2019.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 8/18/2022, 2/16/2024, and 12/03/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Election/Restriction
In the response filed on 12/03/2025, Applicant elected without traverse:
Group I, claims 1-32
Species:
Cetuximab as the EGFR inhibitor
Cobimetinib as the MEK ½ inhibitor
Palbociclib as the CDK 4/6 inhibitor
KRAS G13D as the mutation
Status of Claims
Claims 1-32, and 52 are currently pending and presented for examination on the merits.
Claims 33-51, and 53-64 are canceled.
Claims 4-6, 8-15, 17-18, 21, 27, and 52 are withdrawn from further consideration by Examiner under 37 CFR 1.142(b) as being drawn to a non-elected invention.
Claims 1-3, 7, 16, 19-20, 22-26, and 28-32 are currently under review.
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.
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 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.
Claims 1-3, 7, 16, 19-20, 22-26, and 28-32 are rejected under 35 U.S.C. 103 as being unpatentable over Ziemke et al (Sensitivity of KRAS-Mutant Colorectal Cancers to Combination Therapy that Co-Targets MEK and CDK4/6, Clin Cancer Res. 2016 January 15; 22(2): 405–414, IDS 8/18/2022), and further in view of Zhang et al (WO2018218633 A1, IDS 8/18/2022).
In regards to claims 1-2, 25-26, and 32, Ziemke et al teaches a method of treating colorectal cancer [Abstract]. Ziemke et al further teaches administering daily doses with either agent alone or concurrently [Abstract]. Ziemke et al further teaches treating colorectal cancer with KRAS mutation [Abstract]. Ziemke et al further teaches administering a MEK ½ inhibitor and CDK 4/6 inhibitor with KRAS mutated colorectal cancer [1st Paragraph, pg. 3]. Ziemke et al further teaches administering an EGFR inhibitor in mutant colorectal cancer [1st Paragraph, pg. 2].
Ziemke et al does not specifically teach a method of treating or delaying progression of colorectal cancer in a subject comprising administering to the subject an affective amount of an epidermal growth factor receptor (EGFR) inhibitor; (a) a mitogen-activated protein kinase (MEK) 1/2 inhibitor; and (b) a cyclin dependent kinase (CDK) 4/6 inhibitor; (c) wherein the subject has colorectal cancer that has a KRAS mutation or is at risk of developing colorectal cancer that has a KRAS mutation; however, this deficiency is made up in the teachings of Zhang et al.
Zhang et al teaches cancer treatment comprising administering an EGFR inhibitor, MEK ½ inhibitor, and CDK 4/6 inhibitor [Abstract]. Zhang et al further teaches the cancer is colon cancer or colorectal cancer [3rd Paragraph, pg. 21].
One of ordinary skill, before the effective filing date, would have been motivated to combine Ziemke’s method of treating colorectal cancer that has a KRAS mutation comprising administering a MEK ½ inhibitor and a CDK 4/6 inhibitor or an EGFR inhibitor, with Zhang’s method of treating colorectal cancer comprising administering an EGFR inhibitor, MEK ½ inhibitor and a CDK 4/6 inhibitor. The idea of combining them flows logically from their having been individually taught in the prior art (MPEP 2144.06). Combining prior art elements according to known methods to yield predictable results is an exemplary rationale for a prima facie case of obviousness. MPEP2143. It would have been prima facie obvious to combine Ziemke and Zhang’s methods for a method of treating colorectal cancer with a KRAS mutation comprising administering an EGFR inhibitor, a MEK ½ inhibitor, and a CDK 4/6 inhibitor, because Ziemke teaches all three treatments for the treatment of KRAS mutated colorectal cancer and Zhang teaches administering the three in combination to treat colorectal cancer. Given that the claimed method and that of the prior art comprise the same active steps, there would have been a reasonable expectation that the claimed method and that of the prior art demonstrate the same functional properties, such as those recited in claims 25, 26, and 32.
In regards to claims 3 and 7, Zhang et al teaches an EGFR inhibitor that is cetuximab [Claim 2, pg. 37]. Zhang et al further teaches a MEK ½ inhibitor that is cobimetinib [Claim 3, pg. 37]. Zhang et al further teaches a CDK 4/6 inhibitor that is palbociclib. Claim 4, pg. 37].
Ziemke et al further teaches a EGFR inhibitor that is cetuximab [1st Paragraph, pg. 2]. Ziemke et al further teaches a CDK 4/6 inhibitor that is palbociclib [Abstract].
In regards to claims 16 and 19, Zhang et al further teaches the combination is administering separate or together [Claim 5, pg. 37].
In regards to claims 20, and 22-23, Ziemke et al teaches treating mutant colorectal cancer comprising the activating mutation G13D [3rd Paragraph, pg. 6].
In regards to claim 24, Zhang et al teaches treating epithelial tumors [Abstract]. Zhang et al further teaches the cancer is a malignant epithelial tumor [7th Paragraph, pg. 1].
With regard to claims 28 and 29, the amount of the cobimetinib and palbociclib that is administrated is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ. It would have been customary for an artisan of ordinary skill to determine the optimal amount of each ingredient needed to achieve the desired results. Thus, absent some demonstration of unexpected results from the claimed parameters, the optimization of ingredient amounts would have been obvious at the time of applicant's invention.
In regards to claim 30, Zhang et al teaches administering the treatment by infusion [3rd Paragraph, pg. 24].
With regard to infusion rates, the amount of the cetuximab that is administrated is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ. It would have been customary for an artisan of ordinary skill to determine the optimal amount of each ingredient needed to achieve the desired results. Thus, absent some demonstration of unexpected results from the claimed parameters, the optimization of ingredient amounts would have been obvious at the time of applicant's invention.
The principle of law states from MPEP 2144.05: "The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages."(Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382); 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).
In regards to claim 31, Ziemke et al teaches the cancer is a human colorectal cancer [1st Paragraph, pg. 2].
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.
Claim1-3, 7, 16, 19-20, 22-26, and 28-32 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, and 7-9 of U.S. Patent No. 12076399 ('399) in view of Ziemke et al (Sensitivity of KRAS-Mutant Colorectal Cancers to Combination Therapy that Co-Targets MEK and CDK4/6, Clin Cancer Res. 2016 January 15; 22(2): 405–414, IDS 8/18/2022) and Zhang et al (WO2018218633 A1, IDS 8/18/2022).
The teachings of Ziemke et al and Zhang et al are discussed above.
The difference between instant claim 1 and claim 1 of ‘399 is ‘399 is a method of treating colorectal cancer that does not require KRAS mutation. However, Ziemke et al and Zhang et al teaches treating colorectal cancer with KRAS mutations with an EGFR inhibitor, such as cetuximab, MEK ½ inhibitor, and a CDK 4/6 inhibitor.
One of ordinary skill, at the effective filing date, would have been motivated to adapt the ‘399 method of treating cancer comprising administering a EGFR inhibitor, a MEK ½ inhibitor, and a CDK 4/6 inhibitor, with Ziemke and Zhang’s method of treating colorectal cancer that has a KRAS mutation comprising administering a MEK ½ inhibitor and a CDK 4/6 inhibitor or a EGFR inhibitor, such as cetuximab. The idea of combining them flows logically from their having been individually taught in the prior art (MPEP 2144.06). Combining prior art elements according to known methods to yield predictable results is an exemplary rationale for a prima facie case of obviousness. MPEP2143. It would have been prima facie obvious to combine ‘399 and Ziemke and Zhang’s methods for a method of treating KRAS mutated colorectal cancer comprising administering a EGFR inhibitor, such as cetuximab, a MEK ½ inhibitor, and a CDK 4/6 inhibitor. The invention of the conflicting claims, Ziemke et al, and Zhang et al meets the limitations of claims 1, 2, 25, 26, and 32. Given that the claimed method and that of the prior art comprise the same active steps, there would have been a reasonable expectation that the claimed method and that of the prior art demonstrate the same functional properties, such as those recited in claims 25, 26, and 32.
In regards to claims 3 and 7, Zhang et al teaches an EGFR inhibitor that is cetuximab [Claim 2, pg. 37]. Zhang et al further teaches a MEK ½ inhibitor that is cobimetinib [Claim 3, pg. 37]. Zhang et al further teaches a CDK 4/6 inhibitor that is palbociclib. Claim 4, pg. 37].
Ziemke et al further teaches a EGFR inhibitor that is cetuximab [1st Paragraph, pg. 2]. Ziemke et al further teaches a CDK 4/6 inhibitor that is palbociclib [Abstract].
In regards to claims 16 and 19, Zhang et al further teaches the combination is administering separate or together [Claim 5, pg. 37].
In regards to claims 20, and 22-23, Ziemke et al teaches treating mutant colorectal cancer comprising the activating mutation G13D [3rd Paragraph, pg. 6].
In regards to claim 24, Zhang et al teaches treating epithelial tumors [Abstract]. Zhang et al further teaches the cancer is a malignant epithelial tumor [7th Paragraph, pg. 1].
With regard to claims 28 and 29, the amount of the cobimetinib and palbociclib that is administrated is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ. It would have been customary for an artisan of ordinary skill to determine the optimal amount of each ingredient needed to achieve the desired results. Thus, absent some demonstration of unexpected results from the claimed parameters, the optimization of ingredient amounts would have been obvious at the time of applicant's invention.
In regards to claim 30, Zhang et al teaches administering the treatment by infusion [3rd Paragraph, pg. 24].
With regard to infusion rates, the amount of the cetuximab that is administrated is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ. It would have been customary for an artisan of ordinary skill to determine the optimal amount of each ingredient needed to achieve the desired results. Thus, absent some demonstration of unexpected results from the claimed parameters, the optimization of ingredient amounts would have been obvious at the time of applicant's invention.
The principle of law states from MPEP 2144.05: "The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages."(Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382); 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).
In regards to claim 31, Ziemke et al teaches the cancer is a human colorectal cancer [1st Paragraph, pg. 2].
Claims 1-3, 7, 16, 19-20, 22-26, and 28-32 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, 6-8, 10-18, and 21-23 of U.S. Patent No. 11753476 ('476) in view of Ziemke et al (Sensitivity of KRAS-Mutant Colorectal Cancers to Combination Therapy that Co-Targets MEK and CDK4/6, Clin Cancer Res. 2016 January 15; 22(2): 405–414, IDS 8/18/2022) and Zhang et al (WO2018218633 A1, IDS 8/18/2022).
The teachings of Ziemke et al and Zhang et al are discussed above.
The difference between instant claim 1 and claim 1 of ‘476 is ‘476 is a method of treating colorectal cancer that does not require KRAS mutation. However, Ziemke et al and Zhang et al teaches treating colorectal cancer with KRAS mutations with an EGFR inhibitor, such as cetuximab, MEK ½ inhibitor, and a CDK 4/6 inhibitor.
One of ordinary skill, at the effective filing date, would have been motivated to adapt ‘476 method of treating cancer comprising administering a EGFR inhibitor, a MEK ½ inhibitor, and a CDK 4/6 inhibitor, with Ziemke and Zhang’s method of treating colorectal cancer that has a KRAS mutation comprising administering a MEK ½ inhibitor and a CDK 4/6 inhibitor or a EGFR inhibitor. The idea of combining them flows logically from their having been individually taught in the prior art (MPEP 2144.06). Combining prior art elements according to known methods to yield predictable results is an exemplary rationale for a prima facie case of obviousness. MPEP2143. It would have been prima facie obvious to combine ‘399 and Ziemke and Zhang’s methods for a method of treating KRAS mutated colorectal cancer comprising administering a EGFR inhibitor, MEK ½ inhibitor, and CDK 4/6 inhibitor.
Claims 7, 16, and 19 are not patentably distinct from claims 13-15 of ‘476. Specifically, the treatment is administered separately or together in one composition, and intermittently.
In regards to claims 20, and 22-23, Ziemke et al teaches treating mutant colorectal cancer comprising the activating mutation G13D [3rd Paragraph, pg. 6].
Claim 24 is not patentably distinct from claim 4 of ‘476. Specifically, the cancer is a malignant epithelial tumor or carcinoma.
Claim 25 is not patentably distinct from claim 18 of ‘476. Specifically, the method reduces cancer cell growth and/or increase cancer cell-killing by about 20-99% more than administration of cetuximab, cobimetinib or a salt thereof, or palbociclib or a salt thereof alone.
Claims 26 and 32 are not patentably distinct from claim 10 of ‘476. Specifically, the method reduces mean tumor volume by about 20-95%
Claim 28 is not patentably distinct from claims 11 and 21 of ‘476. Specifically, cobimetinib or a salt thereof is administered to the subject in a daily dose of about 0.25-1 mg/kg.
Claim 29 is not patentably distinct from claims 12 and 22 of ‘476. Specifically, palbociclib or a salt thereof is administered to the subject in a daily dose of about 1-2.5 mg/kg.
Claim 30 is not patentably distinct from claims 16-17 of ‘476. Specifically, cetuximab is administered to the subject in a weekly dose of about 400 mg/m.sup.2 infused over 120 minutes followed by weekly dose of 250 mg/m.sup.2 infused over 60 minutes, and cetuximab is administered to the subject in a weekly dose of about 400 mg/m.sup.2 infused over 120 minutes with a maximum infusion rate of 10 mg/min, followed by weekly dose of 250 mg/m.sup.2 infused over 60 minutes with a maximum infusion rate of 10 mg/min.
Claim 31 is not patentably distinct from claim 23 of ‘476. Specifically, the subject is human.
Claims 1-3, 7, 16, 19-20, 22-26, and 28-32 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 6-9, 15-17, 25, 32-33, and 35-36 of copending Application No. 18/357,945 (US 20240059778 A1) ('778) in view of Ziemke et al (Sensitivity of KRAS-Mutant Colorectal Cancers to Combination Therapy that Co-Targets MEK and CDK4/6, Clin Cancer Res. 2016 January 15; 22(2): 405–414, IDS 8/18/2022) and Zhang et al (WO2018218633 A1, IDS 8/18/2022).
The teachings of Ziemke et al and Zhang et al are discussed above.
The difference between instant claim 1 and claim 1 of ‘476 is ‘399 is a method of treating colorectal cancer that does not require KRAS mutation. However, Ziemke et al and Zhang et al teaches treating colorectal cancer with KRAS mutations with an EGFR inhibitor, such as cetuximab, MEK ½ inhibitor, and a CDK 4/6 inhibitor.
One of ordinary skill, at the effective filing date, would have been motivated to adapt ‘778 method of treating cancer comprising administering a EGFR inhibitor, a MEK ½ inhibitor, and a CDK 4/6 inhibitor, with Ziemke and Zhang’s method of treating colorectal cancer that has a KRAS mutation comprising administering a MEK ½ inhibitor and a CDK 4/6 inhibitor or a EGFR inhibitor. The idea of combining them flows logically from their having been individually taught in the prior art (MPEP 2144.06). Combining prior art elements according to known methods to yield predictable results is an exemplary rationale for a prima facie case of obviousness. MPEP2143. It would have been prima facie obvious to combine ‘778 and Ziemke and Zhang’s methods for a method of treating KRAS mutated colorectal cancer comprising administering a EGFR inhibitor, MEK ½ inhibitor, and CDK 4/6 inhibitor.
Claim 3 is not patentably distinct from claim 8 of ‘778. Specifically, the EGFR inhibitor is osimertinib or a salt thereof or cetuximab, wherein the MEK 1/2 inhibitor is cobimetinib, trametinib, TAK-733 or a salt of the foregoing, and wherein the CDK 4/6 inhibitor is palbociclib or a salt thereof.
Claim 7 is not patentably distinct from claim 9 of ‘778. Specifically, the method comprises administering an affective amount of osimertinib or a salt thereof, cobimetinib or a salt thereof, and palbociclib or a salt thereof.
Claims 16 and 19 are not patentably distinct from claims 15-17 of ‘778. Specifically, osimertinib or a salt thereof, cobimetinib or a salt thereof, and palbociclib or a salt thereof are administered in one composition, or are administered simultaneously to the subject, or are administered intermittently to the subject, or are administered in one composition.
In regards to claims 20, and 22-23, Ziemke et al teaches treating mutant colorectal cancer comprising the activating mutation G13D [3rd Paragraph, pg. 6].
Claim 24 is not patentably distinct from claim 25 of ‘778. Specifically, the cancer is a malignant epithelial tumor or carcinoma.
Claim 25 is not patentably distinct from claim 32 of ‘778. Specifically, the method reduces cancer cell growth and/or increase cancer cell-killing by about 20-99% more than administration of (a) the EGFR inhibitor, (b) the MEK 1/2 inhibitor or (c) the CDK 4/6 inhibitor alone.
Claim 26 is not patentably distinct from claim 33 of ‘778. Specifically, the method reduces mean tumor volume by about 20-95%.
Claim 28 is not patentably distinct from claim 35 of ‘778. Specifically, cobimetinib or a salt thereof is administered to the subject in a daily dose of about 20-60 mg.
Claim 29 is not patentably distinct from claim 36 of ‘778. Specifically, palbociclib or a salt thereof is administered to the subject in a daily dose of about 75-125 mg.
In regards to claim 30, Saha et al teaches the treatment is administered intravenously [0044].
With regard to infusion rates, the amount of the cetuximab that is administrated is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ. It would have been customary for an artisan of ordinary skill to determine the optimal amount of each ingredient needed to achieve the desired results. Thus, absent some demonstration of unexpected results from the claimed parameters, the optimization of ingredient amounts would have been obvious at the time of applicant's invention.
The principle of law states from MPEP 2144.05: "The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages."(Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382); 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).
In regards to claim 31, Ziemke et al teaches the cancer is a human colorectal cancer [1st Paragraph, pg. 2].
This is a provisional nonstatutory double patenting rejection.
Claims 1-3, 7, 16, 19-20, 22-26, and 28-32 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 6-9, 12, 22, 27, 32-33, and 35-39 of copending Application No. 17/766,724 (US 20230310436) ('436) in view of Ziemke et al (Sensitivity of KRAS-Mutant Colorectal Cancers to Combination Therapy that Co-Targets MEK and CDK4/6, Clin Cancer Res. 2016 January 15; 22(2): 405–414, IDS 8/18/2022) and Zhang et al (WO2018218633 A1, IDS 8/18/2022).
The teachings of Ziemke et al and Zhang are discussed above.
The difference between instant claims 1-2 and claims 1 and 6 of ‘436 is ‘436 is treating colorectal cancer. However, Ziemke et al and Zhang et al teaches treating colorectal cancer with KRAS mutations with a EGFR inhibitor, MEK ½ inhibitor, and CDK 4/6 inhibitor.
One of ordinary skill, at the effective filing date, would have been motivated to adapt ‘436 method of treating cancer comprising administering an EGFR inhibitor, a MEK ½ inhibitor, and a CDK 4/6 inhibitor, with Ziemke and Zhang’s method of treating colorectal cancer that has a KRAS mutation comprising administering a MEK ½ inhibitor and a CDK 4/6 inhibitor or a EGFR inhibitor. The idea of combining them flows logically from their having been individually taught in the prior art (MPEP 2144.06). Combining prior art elements according to known methods to yield predictable results is an exemplary rationale for a prima facie case of obviousness. MPEP2143. It would have been prima facie obvious to combine ‘436 and Ziemke and Tomonaga’s methods for a method of treating KRAS mutated colorectal cancer comprising administering a EGFR inhibitor, MEK ½ inhibitor, and CDK 4/6 inhibitor.
Claim 2 is not patentably distinct from claim 7 of ‘436. Specifically, a KRAS inhibitor is not administered to the subject.
Claim 3 is not patentably distinct from claim 8 of ‘436. Specifically, the EGFR inhibitor is osimertinib or a salt thereof, avitinib or a salt thereof, or cetuximab, wherein the MEK 1/2 inhibitor is cobimetinib or a salt thereof, trametinib or a salt thereof, binimetinib or a salt thereof, or TAK-733 or a salt thereof, and wherein the CDK 4/6 inhibitor is palbociclib or a salt thereof, or abemaciclib or a salt thereof.
Claim 7 is not patentably distinct from claims 9 and 12 of ‘436. Specifically, the method comprises administering an affective amount of osimertinib or a salt thereof, cobimetinib or a salt thereof, and palbociclib or a salt thereof, and the method comprises administering to the subject an affective amount of cetuximab, cobimetinib or a salt thereof, and palbociclib or a salt thereof.
Claims 16 and 19 are not patentably distinct from claim 22 of ‘436. Specifically, cetuximab, cobimetinib or a salt thereof, and palbociclib or a salt thereof are administered in two or three compositions or separately.
In regards to claims 20, and 22-23, Ziemke et al teaches treating mutant colorectal cancer comprising the activating mutation G13D [3rd Paragraph, pg. 6].
Claim 24 is not patentably distinct from claim 27 of ‘436. Specifically, the cancer is a malignant epithelial tumor or carcinoma.
Claim 25 is not patentably distinct from claim 32 of ‘436. Specifically, the method reduces cancer cell growth and/or increase cancer cell-killing by about 20-99% more than administration of (a) the EGFR inhibitor, (b) the MEK 1/2 inhibitor or (c) the CDK 4/6 inhibitor alone.
Claim 26 is not patentably distinct from claim 33 of ‘436. Specifically, the method reduces mean tumor volume by about 20-95%.
Claim 28 is not patentably distinct from claim 35 of ‘436. Specifically, cobimetinib or a salt thereof is administered to the subject in a daily dose of about 20-60 mg.
Claim 29 is not patentably distinct from claim 36 of ‘436. Specifically, palbociclib or a salt thereof is administered to the subject in a daily dose of about 75-125 mg.
Claim 30 is not patentably distinct from claim 37 of ‘436. Specifically, cetuximab is administered to the subject in a weekly dose of about 400 mg/m2 infused over 120 minutes with a maximum infusion rate of 10 mg/min, followed by weekly dose of 250 mg/m2 infused over 60 minutes with a maximum infusion rate of 10 mg/min.
Claim 31 is not patentably distinct from claim 38 of ‘436. Specifically, the subject is a human.
Claim 32 is not patentably distinct from claim 39 of ‘436. Specifically, the method reduces the tumor volume by at least about 85%.
This is a provisional nonstatutory double patenting rejection.
Conclusion
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/DENNIS J SULLIVAN/Examiner, Art Unit 1642
/NELSON B MOSELEY II/Primary Examiner, Art Unit 1642