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 .
Claim Status
Claims 18, 20, 22-24, 29, 32, and 40-47 are cancelled. Claims 1-17, 19, 21, 25-28, 30-31, 33-39, and 48-52 as filed on 03 October 2024 are pending and under examination.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 16 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 16 contains the trademark/trade name Enhertu. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe the antibody-drug conjugate of fam-trastuzumab deructecan-nxki and, accordingly, the identification/description is indefinite.
Claim 16 also contains the parenthetical of “fam-trastuzumab deructecan-nxki” after the trademark of Enhertu. The parenthetical renders the claim and claims dependent on it indefinite because it is unclear whether the limitation within the parenthetical is a preferred example—and therefore not limiting—or is part of the claimed invention. See MPEP § 2173.05(d). It is suggested that Applicant revise the claims to clearly indicate whether the limitation within the parenthetical is limiting or not.
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.
Claims 1-14, 16-17, 19, 21, 25-27, 33-39, and 48-49 are rejected under 35 U.S.C. 103 as being unpatentable over Wickman (WO 2016082044 A1) (IDS), Weisser (WO 2015077891) (PTO-892), Kirschbrown et. al. J. Clin. Pharm. 59(5):702-716. (2019) (IDS), and Eng-Wong (WO 2018136412 A2) (IDS).
Wickman teaches HER2 binding VH and VL domains that match the instant sequences as shown in the table below.
Instant SEQ ID NO:
30-31
20-21
50 & 52
51
Clone ID
6586 VH
3382 VL
5244 VH
5244 VL
Wickman SEQ ID NO:
97-100
69
305-306
297-298
Regarding claims 1, 9, 11-12, and 37, Wickman teaches a method of treating HER2+ tumors using bispecific antigen-binding constructs (abstract and figure 1). Wickman teaches HER2 bispecific binding domain that comprises VH of 6586 (SEQ ID NO: 97-100), VL of 3382 (SEQ ID NO: 69), VH of 5244 (SEQ ID NO: 305-306), VL of 5244 (SEQ ID NO: 297-298) and identifies a combination of these VH and VL domains as variant 10000 or V10000 (page 150 “SEQUENCE TABLE”). V1000 is then the HER2 binding domain of the sequences of instant claims 9 and 11-12 which would have the required binding activity of the bispecific administered in the method of claim 1. Wickman further teaches the VH and VL of variant 5244, which match instant SEQ ID NO: 50-52 as shown in the proceeding table, are present in SEQ ID NO: 295. Wickman teaches the combination of the VH1 of 6586, VH2 of 5244, and VL1 of 3382 is v10000 required by claims 12 and 37 (instant specification page 54 Table A and Table B page 55) and taught by Wickman (Sequence table starting on page 150). Wickman further teaches an antigen binding domain of SEQ ID NO: 97, which matches instant SEQ ID NO: 31, SEQ ID NO: 295, which comprises instant SEQ ID NO: 51-52, and SEQ ID NO: 69, which matches instant SEQ ID NO: 21 (claim 1). Wickman teaches the administration of a 2-tiered dose where one dose is high and the second is low and the doses are administered based on body weight ([00404]-[00407]).
Regarding claims 2-8, Wickman teaches the administration daily, weekly, or monthly (claim 72). Wickman teaches the administration of a 2-tiered dose where one dose is high and the second is low and the doses are administered based on body weight ([00404]-[00407]).
Regarding claim 10, Wickman teaches multiple formulations of the bispecific including where one is a Fab and the other is an scFv (Figure 1).
Regarding claims 13-14, 21 and 48, Wickman teaches Her2+ breast cancer cells (Figure 46, Table D, and [00229]), including the cancer cells with HER2 gene amplification ([0230]).
Regarding claim 16, Wickman teaches the subjects have received previous anti-HER2 therapy and teaches T-DM1 is an anti-HER2 therapy ([00233]).
Regarding claim 17, Wickman also teaches the subjects have not received previous treatment with an anti-HER2 therapy ([00233]).
Regarding claim 19, Wickman teaches the cancer is metastatic (Example 28).
Regarding claims 25-27, Wickman teaches the combination of the bispecific antibodies with one or more chemotherapeutics including oxaliplatin and capecitabine ([00234]), or taxane ([00235]).
Regarding claim 33, Wickman teaches Wickman teaches a method of treating HER2+ tumors using bispecific antigen-binding constructs (abstract and figure 1). Wickman teaches Her2+ breast cancer cells (Figure 46, Table D, and [00229]).
Regarding claims 34-36 and 38-39, Wickman teaches the administration daily, weekly, or monthly (claim 72). Wickman teaches the administration of a 2-tiered dose where one dose is high and the second is low and the doses are administered based on body weight ([00404]-[00407]).Wickman teaches a pharmaceutical kit comprising the antigen-binding fragment and instructions for administration ([00255]). The HER2 binding domains of Wickman bind to the same epitopes of HER2 as pertuzumab and trastuzumab (Table 1).
Wickman does not teach fixed or static doses of the HER2 binding antibody. Wickman does not teach the body weight of the subjects being treated. Wickman does not teach first-line treatment by administration of pertuzumab and trastuzumab.
These deficiencies are filled by Weisser, Kirschbrown and Eng-Wong.
Weisser teaches the HER2 binding bispecific V10000 comprises the VH and VL domains of pertuzumab and trastuzumab (claim 6). This is the HER2 binding bispecific antibody of Wickman and the instant claims.
Kirschbrown teaches method of combined therapy of pertuzumab and trastuzumab in fixed dose in monotherapy and combination of monoclonal antibodies of pertuzumab and trastuzumab (Abstract and Figure 1). Kirschbrown teaches the administration to human subjects that have weight range of 54 to 105 kg (page 706 in col 2 in par 3) and 52.5 to 119.5 kg (page 707 in col 1 in par 1). Kirschbrown teaches a loading dose and maintenance dose with the loading dose being higher (abstract).
Kirschbrown teaches doses including 400, 420, 600, and 1200 mg (Figure 1).
Kirschbrown teaches fixed-dose combination of pertuzumab and trastuzumab reduces treatment burden while also improving efficiency of treatment. The fixed-dose combination therapy decreases IV administration and associated complications including risk of infection, thrombosis, discomfort, and costs. Further, fixed-dose has been shown as effective for multiple antibody cancer therapies including breast cancer (page 703 in lines 5-42).
Regarding claims 1-8, 34-36, and 38-39, Eng-Wong teaches fixed static doses of a combination of pertuzumab and trastuzumab with a dose of 1200 mg and 600 mg of both antibodies (claims 1-2 and 21-24). Eng-Wong teaches administration approximately every two or three weeks (page 11 in lines 13-16).
Regarding claims 17 and 49, Eng-Wong teaches the use of pertuzumab and trastuzumab as first-line treatment of HER2+ cancer including HER2 positive breast cancer (page 3 in lines 25-34 and page 4 in lines 1-5). It would have been obvious at the time the application was filed to substitute the high and low dose body weight based dosing of the bispecific V10000 of the method of treating cancer taught by Wickman with the fixed-dose 2-tiered method of Kirschbrown and Eng-Wong to produce a method of treatment comprising administering V1000 in a 2-tiered fixed dose. One of skill in the art would have been motivated by Kirschbrown teaching administration of pertuzumab and trastuzumab had improved effectiveness at fixed doses and that fixed doses decreased complications associated with IV administration improving patient experience and outcome. Weisser teaches the bispecific V1000 variant of Wickman comprises the VH and VL domains of pertuzumab and trastuzumab, so one of skill in the art would have had a reasonable expectation of success using doses shown effective with pertuzumab and trastuzumab with the V1000 bispecific comprising VH and VL domains of pertuzumab and trastuzumab where Wickman and Kirschbrown, and Eng-Wong all teach the treatment of HER2+ cancer.
Regarding the first line treatment of claim 49, it would have been obvious at the time the application was filed to substitute the patient population of the method of Wickman which included patients that had not been previously treated with HER2 targeted therapy with the first-line treatment of Eng-Wong with of pertuzumab and trastuzumab targeting of HER2 in cancer. One of skill in the art would have been motivated to expand the patient population that the bispecific of Wickman can be used for as it is an effective treatment for HER2+ cancer and its use as a first-line treatment would improve patient outcomes. There would have been a reasonable expectation of success as Wickman and Eng-Wong both teach treatment of HER2+ cancer using pertuzumab and trastuzumab binding of HER2 and the activity of the binding both would not change with administration before or after other chemotherapeutics.
In regards to the specific dosage and interval amounts recited in the instant claims "[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), and see M.P.E.P. § 2144.05 II.A. Moreover, 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). See also Merck & Co. v. Biocraft Labs. Inc., 874 F.2d 804,809, 10 USPQ2d 1843, 1847-48 (Fed. Cir. 1989). This because, as is made clear from the prior art, the determination of the dosage regimen of a known drug is well within the purview of one of ordinary skill in the art at the time the invention was made, and it would have been obvious to one of ordinary skill in the art at the time Applicants' invention was made to determine all operable and optimal intervals of treatment because optimal intervals is an art-recognized result-effective variable which would have been routinely determined and optimized in the pharmaceutical art. The art teaches improvement of fixed dosing at varying doses and varying intervals. The optimization of dose amount and frequency would both be known variables to optimize in routine experimentation. Therefore, it would be conventional and within the skill of the art to identify the optimal dosages administered and optimal intervals to achieve target levels and therapeutically effective doses. Further, it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. It is clear that both the prior art and claimed method perform the same protocol to achieve the same results. It would be conventional and within the skill of the art to determine the optimal treatment regimens. Accordingly, one can see that the courts, over a period of over 50 years, have consistently held that treatment (ie dosage and intervals) optimization is obvious.
Claims 1, 15, 28, and 30-31 are rejected under 35 U.S.C. 103 as being unpatentable over Wickman (WO 2016082044 A1) (IDS), Weisser (WO 2015077891) (PTO-892), Kirschbrown et. al. J. Clin. Pharm. 59(5):702-716. (2019) (IDS), and Eng-Wong (WO 2018136412 A2) (IDS) as applied to claims 1-14, 16-17, 19, 21, 25-27, 33-39, and 48-49 above, and further in view of Zhao et. al. Journal of Hematology & Oncology. 12(50):1-13. (2019) (PTO-892).
The teachings of Wickman, Weisser, Kirschbrown and Eng-Wong from the previous art rejection are incorporated here in full. The combine teachings of Wickman, Kirschbrown, and Eng-Wong teach a method of treating HER2+ cancer by two-tiered fix-dose administration of a biparatopic HER2 binding antigen-binding domain that comprises the HER2 binding trastuzumab as previously described.
Wickman further teaches the treatment of gastric cancer and adenocarcinoma ([0006]) and Figure 38). Wickman teaches the bispecific is more effective than trastuzumab alone ([00486]-[00487]).
The combined teachings of Wickman, Weisser, Kirschbrown, and Eng-Wong do not teach the treatment of HER2+ GEA and the combination with PD-1 binding nivolumab.
These deficiencies are filled by Zhao.
Regarding claim 15, Zhao teaches the treatment of HER2+ GEA with HER2 targeted therapies including trastuzumab. Zhao further teaches HER2 targeted treatment with trastuzumab did not improve outcome with these patients (abstract). Zhao further teaches exploration of novel HER2 binding molecules including bispecific domains that bind 2 HER2 epitopes (page 8 in col 2 in par 1).
Regarding claims 28 and 30-31, Zhao teaches the combination of trastuzumab targeting HER2 with PD-1 binding pembrolizumab and nivolumab to improve anti-tumor activity enhancing T-cell activation (page 8 in col 2 in par 2).
It would have been obvious at the time the application was filed combine the method of treatment comprising the administration of the HER2 binding bispecific V10000 at a two-tiered static dose of the combined teachings of Wickman in in view of Weisser, Kirschbrown, and Eng-Wong in the patient population HER2+ GEA of Zhao. One of skill in the art would have been motivated by the lack of effectiveness of trastuzumab alone in the patient population of Zhao. One of skill in the art would then be motivated to use the more effective bispecific antigen-binding domain of Wickman to improve HER2 targeting and improve patient outcome. There would have been a reasonable expectation of success as Wickman teaches the bispecific is more effective in treating HER2 cancer.
Regarding the combination with PD-1 binding nivolumab, it would have been obvious at the time the application was filed to combine the bispecific HER2 binding molecule of Wickman with nivolumab as taught by Zhao for a method of treating HER2 positive tumors. It first would have been prima facie obvious as a combination of known treatments of HER2 positive cancer as taught by Zhao. Further, one of skill in the art would have been motivated by the explicit teaching of Zhao of combining HER2 targeted therapy with PD-1 binding nivolumab. There would have been a reasonable expectation of success as Zhao explicitly teaches improved effectiveness with the combination of HER2 targeting and nivolumab.
Claims 1, 25-26, and 50-51 are rejected under 35 U.S.C. 103 as being unpatentable over Wickman (WO 2016082044 A1) (IDS), Weisser (WO 2015077891) (PTO-892), Kirschbrown et. al. J. Clin. Pharm. 59(5):702-716. (2019) (IDS), and Eng-Wong (WO 2018136412 A2) (IDS) as applied to claims 1-14, 16-17, 19, 21, 25-27, 33-39, and 48-49 above, and further in view Wagner et. al. BMC Cancer. 19(494):1-9. (2019) (PTO-892).
The teachings of Wickman from the previous art rejection are incorporated here in full.
Wickman teaches the bispecific is more effective than trastuzumab alone ([00486]-[00487]).
Regarding claims 25-26, Wickman teaches the combination of the bispecific antibodies with one or more chemotherapeutics including oxaliplatin and capecitabine ([00234]).
The teachings of Kirschbrown, Weisser, and Eng-Wong from the previous art rejection are incorporated here in full.
Wickman, Weisser, Kirschbrown, and Eng-Wong teaches a method of treating HER2+ cancer by two-tiered fix-dose administration of a biparatopic HER2 binding antigen-binding domain that comprises the HER2 binding pertuzumab and trastuzumab as previously described.
Wickman, Kirschbrown, and Eng-Wong do not teach the treatment of HER2+ cancer in combination with CAPOX which comprises capecitabine administered at 1000 mg/m2 twice a day on 1-14 on a 21 day cycle and oxaliplatin at 130 mg/m2 day 1 of a 21 day cycle or mFOLFOX6 comprising 400 mg/m2 of leucovorin and 85 mg/m2 of oxaliplatin every 2 weeks on day 1 and day 15 of a 28 day cycle.
These deficiencies are filled by Wagner.
Wagner teaches HER2+ gastric tumors with trastuzumab and peruzumab with chemotherapy for improved outcomes (abstract).
Regarding claim 50, mFOLFOX6 comprising 400 mg/m2 of leucovorin and 85 mg/m2 of oxaliplatin by IV every 2 weeks on day 1 and day 15 of a 28 day cycle (page 4 in col 1 in lines 3-8). Wagner teaches the administration of this chemotherapy with HER2 binding antibodies trastuzumab and pertuzumab (Figure 1).
Regarding claim 51, Wagner teaches CapOX chemotherapy comprising capecitabine administered at 1000 mg/m2 twice a day orally on 1-14 on a 21 day cycle and oxaliplatin at 130 mg/m2 day 1 by IV of a 21 day cycle (page 4 in col 1 in lines 3-8). Wagner teaches the administration of this chemotherapy with HER2 binding antibodies trastuzumab and pertuzumab (Figure 1).
It would have been obvious at the time the application was filed to substitute the generic chemotherapeutic regiment of the combined method of administering V10000 at a two-tiered fixed dose as taught by the combination of Wickman, Weisser, Kirschbrown, and Eng-Wong the teaching ofWickman in combination with Weisser, Kirschbrown, and Eng-Wong with the CapOX chemotherapeutics taught by the method of administering a HER2 binding agent with CapOX of Wagner. One of skill in the art would have been motivated by the explicit teaching of Wagner to combine its chemotherapeutic regiments with the HER2 binding agents of trastuzumab and pertuzumab . Weisser teaches the bispecific V10000 of Wickman comprises the VH and VL domains of trastuzumab and pertuzumab, the same HER2 monospecific antibodies used in the method of Wagner. Wickman teaches the bispecific is more effective than monospecific antibodies. There would have been a reasonable expectation of success as it is a combination of known cancer therapeutics used in the same patient population and Wagner explicitly teaches the combination of its chemotherapeutics with the monospecific HER2 antibodies that comprise the bispecific of Wickman for treatment of HER2+ cancers.
Claims 1, 25-26, and 52 are rejected under 35 U.S.C. 103 as being unpatentable over Wickman (WO 2016082044 A1) (IDS), Weisser (WO 2015077891) (PTO-892), Kirschbrown et. al. J. Clin. Pharm. 59(5):702-716. (2019) (IDS), and Eng-Wong (WO 2018136412 A2) (IDS) as applied to claims 1-14, 16-17, 19, 21, 25-27, 33-39, and 48-49 above, and further in view Bystricky et. al. Gastrointestinal Cancer: Targets and Therapy. 41-52 (2011) (PTO-892).
The teachings of Wickman from the previous art rejection are incorporated here in full.
Wickman teaches the bispecific is more effective than trastuzumab alone ([00486]-[00487]).
Regarding claims 25-26, Wickman teaches the combination of the bispecific antibodies with one or more chemotherapeutics including cisplatin and 5-FU ([00234]).
The teachings of Weisser, Kirschbrown, and Eng-Wong from the previous art rejection are incorporated here in full.
Wickman, Weisser, Kirschbrown, and Eng-Wong teaches a method of treating HER2+ cancer by two-tiered fix-dose administration of a biparatopic HER2 binding antigen-binding domain that comprises the HER2 binding pertuzumab and trastuzumab as previously described.
Wickman, Weisser, Kirschbrown, and Eng-Wong do not teach the treatment of HER2+ cancer in combination with FP that comprises cisplatin administered at 80 mg/m2 by IV on day 1 and 5-FU 800 mg/m2 on days 1-5.
These deficiencies are filled by Bystricky.
Bystricky teaches improvement of treatment of HER2+ cancer with chemotherapeutics in combination with HER2 binding trastuzumab (abstract).
FP that comprises cisplatin administered at 80 mg/m2 by IV on day 1 and 5-FU 800 mg/m2 on days 1-5 (page 45 in col 1 in lines 2-5).
It would have been obvious at the time the application was filed to substitute the generic chemotherapeutic regiment of the combined method of treatment for HER2+ cancer comprising the administration of the HER2 bispecific antibody of V1000 and chemotherapeutics of Wickman in view of Weisser, Kirschbrown, and Eng-Wong with the FP chemotherapeutic of the method of treatment of HER2+ cancer taught by Bystricky. First, it would have been prima facie obvious to substitute the generic chemotherapeutics of the method of Wickman with the specific chemotherapeutics of the method of treatment of Bystricky which provides a known in the art effective combination and doses. Second, one of skill in the art would have been motivated by the teaching of Wickman teaching the improved effectiveness of its bispecific V1000 when compared to trastuzumab and Bystricky teaches a method comprising its effective chemotherapeutics with the trastuzumab as a monospecific antibody. There would have been a reasonable expectation of success as it is a combination of known cancer therapeutics used in the same patient population and Wickman and Bystricky explicitly teach the combination of chemotherapeutics with HER2 binding antibodies for treatment of HER2+ cancers.
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 1-14, 16-17, 19, 21, 25-27, 33-39, and 48-49 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 11000598 B2 (PTO-892) in view of Wickman (WO 2016082044 A1) (IDS), Weisser (WO 2015077891) (PTO-892), Kirschbrown et. al. J. Clin. Pharm. 59(5):702-716. (2019) (IDS), and Eng-Wong (WO 2018136412 A2) (IDS).
Instant SEQ ID NO: 31 matches SEQ ID NO: 38, instant SEQ ID NO: 21 matches SEQ ID NO: 26, instant SEQ ID NO: 52 matches SEQ ID NO: 66, and instant SEQ ID NO: 51 matches SEQ ID NO: 65.
Regarding claims 1, 9, 11-12, and 37, the reference patent recites an anti-HER2 biparatopic antibody that comprises the heavy and light chains of the instant claims (claims 1-5).
Regarding claims 38-39, the reference patent recites pharmaceutical compositions (claims 14-17).
The patent does not recite a method of treatment or the dose amount and schedule of the claims.
These deficiencies are filled by Wickman, Weisser, Kirschbrown, and Eng-Wong.
The teachings of Wickman, Weisser, Kirschbrown, and Eng-Wong from the previous rejections under 35 U.S.C. 103 are incorporated here in full.
It would have been obvious at the time the application was filed to combine the biparatopic antibody of the patent with the method of treating HER2+ cancer using a two-tiered and fixed or static dose method as taught by the combination of Wickman, Weisser, Kirschbrown, and Eng-Wong. One of skill in the art would have been motivated by the claims of the patent reciting they are part of a pharmaceutical composition which one of skill in the art would know pharmaceutical compositions are administered to subjects. Further, one of skill in the art would have been motivated by the teaching of Kirschbrown of effectiveness in HER2+ cancers with decreased complications and decreased patient burden. There would have been a reasonable expectation of success as Wickman teaches the same bispecific antibody of the patent for use in a method of treating HER2+ cancers.
In regards to the specific dosage and interval amounts recited in the instant claims "[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), and see M.P.E.P. § 2144.05 II.A. Moreover, 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). See also Merck & Co. v. Biocraft Labs. Inc., 874 F.2d 804,809, 10 USPQ2d 1843, 1847-48 (Fed. Cir. 1989). This because, as is made clear from the prior art, the determination of the dosage regimen of a known drug is well within the purview of one of ordinary skill in the art at the time the invention was made, and it would have been obvious to one of ordinary skill in the art at the time Applicants' invention was made to determine all operable and optimal intervals of treatment because optimal intervals is an art-recognized result-effective variable which would have been routinely determined and optimized in the pharmaceutical art. The art teaches improvement of fixed dosing at varying doses and varying intervals. The optimization of dose amount and frequency would both be known variables to optimize in routine experimentation. Therefore, it would be conventional and within the skill of the art to identify the optimal dosages administered and optimal intervals to achieve target levels and therapeutically effective doses. Further, it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. It is clear that both the prior art and claimed method perform the same protocol to achieve the same results. It would be conventional and within the skill of the art to determine the optimal treatment regimens. Accordingly, one can see that the courts, over a period of over 50 years, have consistently held that treatment (ie dosage and intervals) optimization is obvious.
Claims 1, 15, 28, and 30-31 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 11000598 B2 (PTO-892) in view of Wickman (WO 2016082044 A1) (IDS), Weisser (WO 2015077891) (PTO-892), Kirschbrown et. al. J. Clin. Pharm. 59(5):702-716. (2019) (IDS), Eng-Wong (WO 2018136412 A2) (IDS), and Zhao et. al. Journal of Hematology & Oncology. 12(50):1-13. (2019) (PTO-892).
The patent recitations from the previous rejections are incorporated here in full.
The teachings of Wickman, Weisser, Kirschbrown, and Eng-Wong from the previous rejections under 35 U.S.C. 103 are incorporated here in full.
Patent, Wickman, Kirschbrown, and Eng-Wong do not teach the treatment of HER2+ GEA and the combination with PD-1 binding nivolumab.
These deficiencies are filled by Zhao.
The teachings of Zhao from the previous rejections under 35 U.S.C. 103 are incorporated here in full.
It would have been obvious at the time the application was filed combine the method of treatment comprising the administration of the HER2 binding bispecific V10000 at a two-tiered static dose of the combined teachings of Patent in view of Wickman, Weisser, Kirschbrown, and Eng-Wong in the patient population HER2+ GEA of Zhao. One of skill in the art would have been motivated by the lack of effectiveness of trastuzumab alone in the patient population of Zhao. One of skill in the art would then be motivated to use the more effective bispecific antigen-binding domain of the patent and Wickman to improve HER2 targeting and improve patient outcome. There would have been a reasonable expectation of success as Wickman teaches the bispecific of the patent is more effective in treating HER2 cancer.
Regarding the combination with PD-1 binding nivolumab, it would have been obvious at the time the application was filed to combine the bispecific HER2 binding molecule of the patent and Wickman with nivolumab as taught by Zhao for a method of treating HER2 positive tumors. It first would have been prima facie obvious as a combination of known treatments of HER2 positive cancer as taught by Zhao. Further, one of skill in the art would have been motivated by the explicit teaching of Zhao of combining HER2 targeted therapy with PD-1 binding nivolumab. There would have been a reasonable expectation of success as Zhao explicitly teaches improved effectiveness with the combination of HER2 targeting and nivolumab.
Claims 1, 25-26, and 50-51 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 11000598 B2 (PTO-892) in view of Wickman (WO 2016082044 A1) (IDS), Weisser (WO 2015077891) (PTO-892), Kirschbrown et. al. J. Clin. Pharm. 59(5):702-716. (2019) (IDS), Eng-Wong (WO 2018136412 A2) (IDS), and Wagner et. al. BMC Cancer. 19(494):1-9. (2019) (PTO-892).
The patent recitations from the previous rejections are incorporated here in full.
The teachings of Wickman, Weisser, Kirschbrown, and Eng-Wong from the previous rejections under 35 U.S.C. 103 are incorporated here in full. The Patent, Wickman, Weisser, Kirschbrown, and Eng-Wong teaches a method of treating HER2+ cancer by two-tiered fix-dose administration of a biparatopic HER2 binding antigen-binding domain that comprises the HER2 binding trastuzumab as previously described.
Patent, Wickman, Kirschbrown, and Eng-Wong do not teach the treatment of HER2+ cancer in combination with CAPOX which comprises capecitabine administered at 1000 mg/m2 twice a day on 1-14 on a 21 day cycle and oxaliplatin at 130 mg/m2 day 1 of a 21 day cycle or mFOLFOX6 comprising 400 mg/m2 of leucovorin and 85 mg/m2 of oxaliplatin every 2 weeks on day 1 and day 15 of a 28 day cycle.
These deficiencies are filled by Wagner.
The teachings of Wagner from the previous rejections under 35 U.S.C. 103 are incorporated here in full.
It would have been obvious at the time the application was filed to substitute the generic chemotherapeutic regiment of the combination of the HER2 binding bispecific antibody of V10000 of the Patent in view of Wickman, Weisser, Kirschbrown, and Eng-Wong with the specific chemotherapy of mFOLFOX6taught in the method of Wagner. One of skill in the art would have been motivated by the explicit teaching of Wagner to combine its chemotherapeutic regiments with the HER2 binding agent of the patent and Wickman as Wagner teaches HER2+ cancer treatment with a combination of its chemotherapeutics with a HER2 binding antibody. Further, it would have been a substitution of generic chemotherapeutic administration for taught in the art effective doses. There would have been a reasonable expectation of success as it is a combination of known cancer therapeutics used in the same patient population and Wagner explicitly teaches the combination of its chemotherapeutics with HER2 binding antibodies for treatment of HER2+ cancers.
Claims 1, 25-26, and 52 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 11000598 B2 (PTO-892) in view of Wickman (WO 2016082044 A1) (IDS), Weisser (WO 2015077891) (PTO-892), Kirschbrown et. al. J. Clin. Pharm. 59(5):702-716. (2019) (IDS), Eng-Wong (WO 2018136412 A2) (IDS), and Bystricky et. al. Gastrointestinal Cancer: Targets and Therapy. 41-52 (2011) (PTO-892).
The patent recitations from the previous rejections are incorporated here in full.
The teachings of Wickman, Weisser, Kirschbrown, and Eng-Wong from the previous rejections under 35 U.S.C. 103 are incorporated here in full.
The Patent, Wickman, Weisser, Kirschbrown, and Eng-Wong teaches a method of treating HER2+ cancer by two-tiered fix-dose administration of a biparatopic HER2 binding antigen-binding domain that comprises the HER2 binding trastuzumab as previously described.
Patent, Wickman, Kirschbrown, and Eng-Wong do not teach the treatment of HER2+ cancer in combination with FP that comprises cisplatin administered at 80 mg/m2 by IV on day 1 and 5-FU 800 mg/m2 on days 1-5.
These deficiencies are filled by Bystricky.
The teachings of Bystricky from the previous rejections under 35 U.S.C. 103 are incorporated here in full.
It would have been obvious at the time the application was filed to substitute the generic chemotherapeutic regiment of the method of treatment comprising the HER2 binding bispecific of V1000 of the patent in view of Wickman, Weisser, Kirschbrown, and Eng-Wong with the specific chemotherapy of 5-FU and cisplatin of Bystricky. One of skill in the art would have been motivated by the explicit teaching of Bystricky to combine its chemotherapeutic regiments with the HER2 binding agent of the patent and Wickman as Wagner teaches HER2+ cancer treatment with a combination of its chemotherapeutics with a HER2 binding antibody. Further, it would have been a substitution of generic chemotherapeutic administration for taught in the art effective doses. There would have been a reasonable expectation of success as it is a combination of known cancer therapeutics used in the same patient population and Bystricky explicitly teaches the combination of its chemotherapeutics with HER2 binding antibodies for treatment of HER2+ cancers.
Claims 1-14, 16-17, 19, 21, 25-27, 33-39, and 48-49 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-33 of U.S. Patent No. 12357701 B2 (PTO-892) in view of Wickman (WO 2016082044 A1) (IDS), Weisser (WO 2015077891) (PTO-892), Kirschbrown et. al. J. Clin. Pharm. 59(5):702-716. (2019) (IDS), and Eng-Wong (WO 2018136412 A2) (IDS).
Instant SEQ ID NO: 31 matches SEQ ID NO: 38, instant SEQ ID NO: 21 matches SEQ ID NO: 26, instant SEQ ID NO: 52 matches SEQ ID NO: 66, and instant SEQ ID NO: 51 matches SEQ ID NO: 65.
The patent recites a method of treating HER+ cancer using the antibody of the instant claims (claim 1).
The patent recites breast cancer, ovarian cancer, lung cancer, and gastric cancer (claim 2).
The patent recites the bispecific comprises a Fab and scFv binding domain (claim 18).
The patent does not recite a method of treatment or the dose amount and schedule of the claims.
The teachings of Wickman, Weisser, Kirschbrown, and Eng-Wong from the previous rejections under 35 U.S.C. 103 are incorporated here in full.
The teachings of Wickman, Kirschbrown, and Eng-Wong from the previous art and double patenting rejections are incorporated here in full.
It would have been obvious at the time the application was filed to combine the biparatopic antibody of the patent with the method of treating HER2+ cancer using a two-tiered and fixed or static dose method as taught by the combination of Wickman, Weisser, Kirschbrown, and Eng-Wong. One of skill in the art would have been motivated by the claims of the patent reciting they are part of a pharmaceutical composition which one of skill in the art would know pharmaceutical compositions are administered to subjects. The bispecific of the patent, Wickman, and Weisser are the same HER2 binding bispecific of V10000 which Wickman teaches as an effective therapeutic for treating HER2+ cancer. Further, one of skill in the art would have been motivated by the teaching of Kirschbrown of effectiveness in HER2+ cancers with decreased complications and decreased patient burden. There would have been a reasonable expectation of success as Wickman teaches the same bispecific antibody of the patent for use in a method of treating HER2+ cancers. In regards to the specific dosage and interval amounts recited in the instant claims "[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), and see M.P.E.P. § 2144.05 II.A. Moreover, 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). See also Merck & Co. v. Biocraft Labs. Inc., 874 F.2d 804,809, 10 USPQ2d 1843, 1847-48 (Fed. Cir. 1989). This because, as is made clear from the prior art, the determination of the dosage regimen of a known drug is well within the purview of one of ordinary skill in the art at the time the invention was made, and it would have been obvious to one of ordinary skill in the art at the time Applicants' invention was made to determine all operable and optimal intervals of treatment because optimal intervals is an art-recognized result-effective variable which would have been routinely determined and optimized in the pharmaceutical art. The art teaches improvement of fixed dosing at varying doses and varying intervals. The optimization of dose amount and frequency would both be known variables to optimize in routine experimentation. Therefore, it would be conventional and within the skill of the art to identify the optimal dosages administered and optimal intervals to achieve target levels and therapeutically effective doses. Further, it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. It is clear that both the prior art and claimed method perform the same protocol to achieve the same results. It would be conventional and within the skill of the art to determine the optimal treatment regimens. Accordingly, one can see that the courts, over a period of over 50 years, have consistently held that treatment (ie dosage and intervals) optimization is obvious.
Claims 1, 15, 28, and 30-31 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-33 of U.S. Patent No. 12357701 B2 (PTO-892) in view of Wickman (WO 2016082044 A1) (IDS), Weisser (WO 2015077891) (PTO-892), Kirschbrown et. al. J. Clin. Pharm. 59(5):702-716. (2019) (IDS), Eng-Wong (WO 2018136412 A2) (IDS), and Zhao et. al. Journal of Hematology & Oncology. 12(50):1-13. (2019) (PTO-892).
The patent recitations from the previous rejections are incorporated here in full.
The teachings of Wickman, Weisser, Kirschbrown, and Eng-Wong from the previous rejections under 35 U.S.C. 103 are incorporated here in full.
The Patent in view of Wickman, Weisser, Kirschbrown, and Eng-Wong teaches a method of treating HER2+ cancer by two-tiered fix-dose administration of a biparatopic HER2 binding antigen-binding domain that comprises the HER2 binding VH and VL domains of trastuzumab and pertuzumab as previously described.
Patent, Wickman, Kirschbrown, and Eng-Wong do not teach the treatment of HER2+ GEA and the combination with PD-1 binding nivolumab.
These deficiencies are filled by Zhao.
The teachings of Zhao from the previous rejections under 35 U.S.C. 103 are incorporated here in full.
It would have been obvious at the time the application was filed to use the method of treating HER+ cancer using the HER2 binding biparatopic of the patent in view of Wickman, Weisser, Kirschbrown, and Eng-Wong in the HER2+ GEA patient population of Zhao. One of skill in the art would have been motivated by the lack of effectiveness of trastuzumab alone in the patient population of Zhao. One of skill in the art would then be motivated to use the more effective bispecific antigen-binding domain of the patent and Wickman, taught by Weisser as V1000 that comprises trastuzumab and pertuzumab, to improve HER2 targeting and improve patient outcome. There would have been a reasonable expectation of success as Wickman teaches the bispecific V10000 is more effective in treating HER2 cancer.
Regarding the combination with PD-1 binding nivolumab, it would have been obvious at the time the application was filed to combine the bispecific HER2 binding molecule of the patent and Wickman with nivolumab as taught by Zhao for a method of treating HER2 positive tumors. It first would have been prima facie obvious as a combination of known treatments of HER2 positive cancer as taught by Zhao. Further, one of skill in the art would have been motivated by the explicit teaching of Zhao of combining HER2 targeted therapy with PD-1 binding nivolumab. There would have been a reasonable expectation of success as Zhao explicitly teaches improved effectiveness with the combination of HER2 targeting and nivolumab.
Claims 1, 25-26, and 50-51 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-33 of U.S. Patent No. 12357701 B2 (PTO-892) in view of Wickman (WO 2016082044 A1) (IDS), Weisser (WO 2015077891) (PTO-892), Kirschbrown et. al. J. Clin. Pharm. 59(5):702-716. (2019) (IDS), Eng-Wong (WO 2018136412 A2) (IDS), and Wagner et. al. BMC Cancer. 19(494):1-9. (2019) (PTO-892).
The patent recitations from the previous rejections are incorporated here in full.
The teachings of Wickman, Weisser, Kirschbrown, and Eng-Wong from the previous rejections under 35 U.S.C. 103 are incorporated here in full.
The Patent, Wickman, Weisser, Kirschbrown, and Eng-Wong teaches a method of treating HER2+ cancer by two-tiered fix-dose administration of a biparatopic HER2 binding antigen-binding domain that comprises the HER2 binding VH and VL domains of trastuzumab and pertuzumab as previously described.
Patent, Wickman, Weisser, Kirschbrown, and Eng-Wong do not teach the treatment of HER2+ cancer in combination with CAPOX which comprises capecitabine administered at 1000 mg/m2 twice a day on 1-14 on a 21 day cycle and oxaliplatin at 130 mg/m2 day 1 of a 21 day cycle or mFOLFOX6 comprising 400 mg/m2 of leucovorin and 85 mg/m2 of oxaliplatin every 2 weeks on day 1 and day 15 of a 28 day cycle.
These deficiencies are filled by Wagner.
The teachings of Wagner from the previous rejections under 35 U.S.C. 103 are incorporated here in full.
It would have been obvious at the time the application was filed to substitute the generic chemotherapeutic regiment of the combination of the bispecific of Patent in view of Wickman, Weisser, Kirschbrown, and Eng-Wong with the specific the specific chemotherapeutic of CapOX taught by the method of Wagner. One of skill in the art would have been motivated by the explicit teaching of Wagner to combine its chemotherapeutic regiments with the HER2 binding agent of the patent and Wickman as Wagner teaches HER2+ cancer treatment with a combination of its chemotherapeutics with a HER2 binding antibody. Further, it would have been a substitution of generic chemotherapeutic administration for taught in the art effective doses. There would have been a reasonable expectation of success as it is a combination of known cancer therapeutics used in the same patient population and Wagner explicitly teaches the combination of its chemotherapeutics with HER2 binding antibodies for treatment of HER2+ cancers.
Claims 1, 25-26, and 52 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-33 of U.S. Patent No. 12357701 B2 (PTO-892) in view of Wickman (WO 2016082044 A1) (IDS), Weisser (WO 2015077891) (PTO-892), Kirschbrown et. al. J. Clin. Pharm. 59(5):702-716. (2019) (IDS), Eng-Wong (WO 2018136412 A2) (IDS), and Bystricky et. al. Gastrointestinal Cancer: Targets and Therapy. 41-52 (2011) (PTO-892).
The patent recitations from the previous rejections are incorporated here in full.
The teachings of Wickman, Weisser, Kirschbrown, and Eng-Wong from the previous rejections under 35 U.S.C. 103 are incorporated here in full.
The Patent, Wickman,Weisser, Kirschbrown, and Eng-Wong teaches a method of treating HER2+ cancer by two-tiered fix-dose administration of a biparatopic HER2 binding antigen-binding domain that comprises the HER2 binding trastuzumab as previously described.
Patent, Wickman, Kirschbrown, and Eng-Wong do not teach the treatment of HER2+ cancer in combination with FP that comprises cisplatin administered at 80 mg/m2 by IV on day 1 and 5-FU 800 mg/m2 on days 1-5.
These deficiencies are filled by Bystricky.
The teachings of Bystricky from the previous rejections under 35 U.S.C. 103 are incorporated here in full.
It would have been obvious at the time the application was filed to substitute the generic chemotherapeutic regiment of the method of administering the bispecific HER2 binding antibody in combination with chemotherapeutics of Patent in view of Wickman, Weisser, Kirschbrown, and Eng-Wong with the specific chemotherapeutics of the method of treatment for HER2+ cancer of Bystricky. One of skill in the art would have been motivated by the explicit teaching of Bystricky to combine its chemotherapeutic regiments with the HER2 binding agent of the Patent and Wickman as Wagner teaches HER2+ cancer treatment with a combination of its chemotherapeutics with a HER2 binding antibody. Further, it would have been a substitution of generic chemotherapeutic administration for taught in the art effective doses. There would have been a reasonable expectation of success as it is a combination of known cancer therapeutics used in the same patient population and Bystricky explicitly teaches the combination of its chemotherapeutics with HER2 binding antibodies for treatment of HER2+ cancers.
Conclusion
No claims allowable.
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/F.E./Examiner, Art Unit 1643
/JULIE WU/Supervisory Patent Examiner, Art Unit 1643
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