DETAILED ACTION
Claims filed 12/22/2023 are acknowledged and entered into the record.
Accordingly, Claims 1-20 are pending and will be examined on the merits.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
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 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.
Claims 1-20 are rejected under 35 U.S.C. 103 as being unpatentable over #NCT01148849 Clinical Trial (Safety Study of MGAH22 in HER2-positive Carcinomas, ClinicalTrials.gov archive, Submitted date September 25, 2013, cited on IDS filed 5/7/2024) in view of Johnson et al. (US Patent 8802093 and WO/2009/123894, published 10/8/2009 with the same disclosure, cited on IDS filed 5/7/2024).
The claims are drawn to a method of treating a HER2/neu-expressing cancer in a subject comprising administering a chimeric 4D5 mutant having a N65S mutation as depicted in light chain variable domain sequences having SEQ ID NO: 4 and variable heavy chain sequences having SEQ ID NOs 9, 11, and 13, wherein a first dose is followed by a second dose at 10, 15, or 18 mg/kg of subject weight and administered by IV infusion over a period of 30-180 minutes and a subsequent equal does is given every 3 weeks for a minimum of 6 months. Instant Claim 10 is drawn to wherein the treatment further comprises the step of administering a second therapeutic agent simultaneously or sequentially with the chimeric 4D5 antibody.
Clinical Trial #NCT01148849A is a Phase 1, Dose Escalation Study of MGAH22 in Patients With Refractory HER2 Positive Breast Cancer and Patients With Other HER2 Positive Carcinomas for Whom No Standard Therapy Is Available started in July of 2010. A study status was published on ClinicalTrials.gov on September 25, 2013. MGAH22, also known as Margetuximab, is an Fc modified chimeric monoclonal antibody directed against the HER2 receptor. Applicants state in the response filed 09/3/2020 on page 8 that margetuximab/MGAH22 corresponds to ch4D5-FcMT2 disclosed in the instant specification having a light chain with instant SEQ ID NO: 4 and a heavy chain with instant SEQ ID NO: 11. The purpose of the phase I study is to determine if MGAH22 is safe when given by intravenous (IV) infusion to patients with HER2-positive cancer. The study will also evaluate how long MGAH22 stays in the blood and how long it takes for it to leave the body, what is the highest dose that can safely be given, and whether it has an effect on tumors. MGAH22 will be administered by IV infusion once every 3 weeks in the following dose escalation cohorts: 10.0 and 15.0 mg/kg. The clinical trial therefore teaches administering the same chimeric 4D5 antibody at a repeat dose of 15 mg/kg intravenously every 3 weeks to the same breast cancer patient population instantly claimed. The clinical trial however does not explicitly state the duration of the study (ie: 6 months or more), however it recites “responding patients may receive continued antibody therapy until evidence of progression of disease is documented or the patient experiences DLT. #NCT01148849A Clinical trial does not teach further treatment with a second therapeutic agent. This deficiency is made up for by Johnson et al.
Johnson et al. (both US Patent 8802093 and WO/2009/123894) teach antibodies that specifically bind HER2/neu, and particularly chimeric 4D5 antibodies to HER2/neu. Johnson et al. also teach methods of using the 4D5 antibodies and compositions comprising them in the diagnosis, prognosis and therapy of diseases such as cancer, autoimmune diseases, inflammatory disorders, and infectious disease. Johnson et al. teach the same HER2/neu chimeric antibody instantly claimed with the N65S mutation depicted in instant SEQ ID NO: 4 and variable heavy chains having instant SEQ ID NOs: 9, 11 and 13. Johnson et al. disclose “the step of administering a second therapeutic agent simultaneously or sequentially with the antibody, wherein the second therapeutic agent is selected from the group consisting of an anti-angiogenic agent, an anti-neoplastic agent, a chemotherapeutic agent, and a cytotoxic agent” (see paragraph [0040]). Johnson et al. further disclose “In certain embodiments, the therapeutic agents are cyclically administered to a subject. Cycling therapy involves the administration of a first agent for a period of time, followed by the administration of a second agent and/or third agent for a period of time and repeating this sequential administration. Cycling therapy can reduce the development of resistance to one or more of the therapies, avoid or reduce the side effects of one of the therapies, and/or improves the efficacy of the treatment.”
It would have been prima facie obvious to on one of ordinary skill in the art before the effective filing date of the claimed invention to expand the #NCT01148849A Clinical trial to further administer a second therapeutic agent to achieve maximal therapeutic benefit. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success based on the teachings of #NCT01148849A clinical trial and Johnson et al. that chimeric 4D5 was well tolerated and that a second agent can help reduce the development of resistance, avoid or reduce side effects and or improve efficacy of treatment. Therefore, it would be obvious to one of ordinary skill in the art, at the time the invention was made, to expand the treatment taught by #NCT01148849A Clinical trial to include administering a second therapeutic agent to improve efficacy of treatment.
Additionally, it would have been prima facie obvious to on one of ordinary skill in the art before the effective filing date of the claimed invention to administer the chimeric 4D5 antibody according to the dosing and schedule regimens taught by #NCT01148849A Clinical Trial of 15 mg/kg every 3 weeks for a period of time 6 months or longer. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success based on the disclosure of the clinical trial stating “Responding patients may receive continued antibody therapy until evidence of progression of disease is documented or the patient experiences DLT.“ Furthermore, in regards to the exact dosage amounts and times instantly claimed, it is well settled that "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." In re Boesch, 617 F.2d 272, 276, 205 USPQ 215, 219 (CCPA 1980). Therefore, it would be obvious to one of ordinary skill in the art, at the time the invention was made, to optimize dosage ranges/times by routine experimentation and anticipate the dosage ranges/times cited in the instant claims, especially when the dosage amounts taught in the prior art are the same dosage and schedule as instantly claimed.
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 §§ 706.02(l)(1) - 706.02(l)(3) 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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 9,243,069 in view of #NCT01148849 Clinical Trial (Safety Study of MGAH22 in HER2-positive Carcinomas, ClinicalTrials.gov archive, Submitted date September 25, 2013). Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims and those of US Patent 9,243,069 are both drawn to methods of treatment comprising administering the same chimeric 4D5 antibody to the same patient population. It would be routine and obvious to optimize the dosage amount and schedule of the method of treatment claimed in US Patent 9,243,069 to that taught by #NCT01148849 Clinical Trial of 15mg/kg every 3 weeks for a minimum of 6 months.
Clinical Trial #NCT01148849A is a Phase 1, Dose Escalation Study of MGAH22 in Patients With Refractory HER2 Positive Breast Cancer and Patients With Other HER2 Positive Carcinomas for Whom No Standard Therapy Is Available started in July of 2010. A study status was published on ClinicalTrials.gov on September 25, 2013. MGAH22, also known as Margetuximab, is an Fc modified chimeric monoclonal antibody directed against the HER2 receptor. Applicants state in the response filed 09/3/2020 on page 8 that margetuximab/MGAH22 corresponds to ch4D5-FcMT2 disclosed in the instant specification having a light chain with instant SEQ ID NO:2 or 4 and a heavy chain with instant SEQ ID NO: 11. The purpose of the phase I study is to determine if MGAH22 is safe when given by intravenous (IV) infusion to patients with HER2-positive cancer. The study will also evaluate how long MGAH22 stays in the blood and how long it takes for it to leave the body, what is the highest dose that can safely be given, and whether it has an effect on tumors. MGAH22 will be administered by IV infusion once every 3 weeks in the following dose escalation cohorts: 10.0 and 15.0 mg/kg.
It would have been prima facie obvious to on one of ordinary skill in the art before the effective filing date of the claimed invention to administer the chimeric 4D5 antibody according to the dosing and schedule regimens taught by #NCT01148849A Clinical Trial of 15 mg/kg every 3 weeks for a minimum of 6 months. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success based on the disclosure of the clinical trial stating “Responding patients may receive continued antibody therapy until evidence of progression of disease is documented or the patient experiences DLT.” Furthermore, in regards to the exact dosage amounts and times instantly claimed, it is well settled that "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." In re Boesch, 617 F.2d 272, 276, 205 USPQ 215, 219 (CCPA 1980). Therefore, it would be obvious to one of ordinary skill in the art, at the time the invention was made, to optimize dosage ranges/times by routine experimentation and anticipate the dosage ranges/times cited in the instant claims, especially when the dosage amounts taught in the prior art are the same dosage and schedule as instantly claimed.
Claims 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 10,131,713 in view of #NCT01148849 Clinical Trial (Safety Study of MGAH22 in HER2-positive Carcinomas, ClinicalTrials.gov archive, Submitted date September 25, 2013). Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims and those of US Patent 10,131,713 are both drawn to methods of treatment comprising administering the same chimeric 4D5 antibody to the same patient population. It would be routine and obvious to optimize the dosage amount and schedule of the method of treatment claimed in US Patent 10,131,713 to that taught by #NCT01148849 Clinical Trial of 15mg/kg every 3 weeks for a minimum of 6 months.
Clinical Trial #NCT01148849A is a Phase 1, Dose Escalation Study of MGAH22 in Patients With Refractory HER2 Positive Breast Cancer and Patients With Other HER2 Positive Carcinomas for Whom No Standard Therapy Is Available started in July of 2010. A study status was published on ClinicalTrials.gov on September 25, 2013. MGAH22, also known as Margetuximab, is an Fc modified chimeric monoclonal antibody directed against the HER2 receptor. Applicants state in the response filed 09/3/2020 on page 8 that margetuximab/MGAH22 corresponds to ch4D5-FcMT2 disclosed in the instant specification having a light chain with instant SEQ ID NO:2 or 4 and a heavy chain with instant SEQ ID NO: 11. The purpose of the phase I study is to determine if MGAH22 is safe when given by intravenous (IV) infusion to patients with HER2-positive cancer. The study will also evaluate how long MGAH22 stays in the blood and how long it takes for it to leave the body, what is the highest dose that can safely be given, and whether it has an effect on tumors. MGAH22 will be administered by IV infusion once every 3 weeks in the following dose escalation cohorts: 10.0 and 15.0 mg/kg.
It would have been prima facie obvious to on one of ordinary skill in the art before the effective filing date of the claimed invention to administer the chimeric 4D5 antibody according to the dosing and schedule regimens taught by #NCT01148849A Clinical Trial of 15 mg/kg every 3 weeks for a minimum of 6 months. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success based on the disclosure of the clinical trial stating “Responding patients may receive continued antibody therapy until evidence of progression of disease is documented or the patient experiences DLT.” Furthermore, in regards to the exact dosage amounts and times instantly claimed, it is well settled that "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." In re Boesch, 617 F.2d 272, 276, 205 USPQ 215, 219 (CCPA 1980). Therefore, it would be obvious to one of ordinary skill in the art, at the time the invention was made, to optimize dosage ranges/times by routine experimentation and anticipate the dosage ranges/times cited in the instant claims, especially when the dosage amounts taught in the prior art are the same dosage and schedule as instantly claimed.
Conclusion
Claims 1-20 are rejected.
No Claim is allowed.
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/Meera Natarajan/Primary Examiner, Art Unit 1643
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