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 .
Priority
The instant application, filed 07/28/2023, claims domestic benefit to US provisional application 63/369,931, filed 07/29/2022.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 03/28/24 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
Status of Claims
The preliminary amendment of claims filed on 12/15/2023 is acknowledged. Claims 1-27, filed on 07/28/2023, are currently pending and are examined on the merits herein.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim 1-5, 7-11, and 13-27 are rejected under 35 U.S.C. 103 as being unpatentable over Powderly et al., 2020 (Powderly, et al., "596TiP Phase I First-in-Human Study of ABBV-151 as Monotherapy or in Combination with Budigalimab in Patients with Locally Advanced or Metastatic Solid Tumours", Annals of Oncology (2020), Vol. 31, Abstract. Listed in the IDS) and in further view of Van der Woning 2018 (WO2018/206790 A1, published on 11/15/2018, herein referred to as Van Der Woning 2018); Italiano et al., 2021 (Italiano et al., "First-in-human Phase 1 Study of Budigalimab, An Anti-PD-1 Inhibitor, in Patients with non-small Cell Lung Cancer and head and Neck Squamous Cell Carcinoma", Cancer Immunology Immunotherapy, Springer, Berlin/Heidelberg (2021), Vol. 71:2, pp.1-15. Listed in the IDS); NCT03821935, 2022 (Clinicaltrials.gov, NCT03821935, version 18, published 06/29/2022, website: https://clinicaltrials.gov/study/NCT03821935?tab=history&a=18#version-content-panel) and as evidenced by ArgenX, 2022 (ArgenX, Case Study: ARGX-115, updated on 07/01/2022, Website: https://web.archive.org/web/20220701192916/https://argenx.com/case-studies/argx-115); and Spallanzani et al., 2018 (Spallanzani et al. Immunotherapy in the treatment of colorectal cancer: a new kid on the block. J Cancer Metastasis Treat. 2018;4:28. http://dx.doi.org/10.20517/2394-4722.2018.31).
Regarding instant claims 1, 3, 5, 8, 10, 13, 15, 17, 19, and 24, Powderly et al., 2020 teaches a method of treating locally advanced or metastatic solid tumors with ABBV-151 and budigalimab (page 1, column 1, title). Livmoniplimab is also known as ABBV-151 and defined by the applicant as a first in-class monoclonal antibody that blocks GARP-TGF[Symbol font/0x62]1 complex and blocks TGF[Symbol font/0x62]1 release (applicant's disclosure, page 1, paragraph 0005, “WO 2018/206790 [Van der Woning 2018] describes the humanization of ABBV-151 (livmoniplimab) a monoclonal antibody that specifically binds to the GARP-TGF-[Symbol font/0x62] 1 complex, blocking release of active TGF-[Symbol font/0x62] 1”).
Further, Powderly et al., 2020 teaches a dose escalation clinical trial of ABBV-151, to assess dose-limiting toxicities during the first 28-day cycle and is utilized until the recommended phase II dose (RP2D) is defined (page 1, column 1, Trial Design) but does not teach the doses of the livmoniplimab (ABBV-151). Van Der Woning 2018 teaches dose ranges of the anti-GARP-TGF[Symbol font/0x62] 1 antibody ARGX-115 (page 13, Figure 19 Description and page 47, paragraph 1, line 1-5, "about 0.01 to about 100 mg/kg body weight. In an embodiment, a single dose of the antibody or antigen binding fragment can be, for example, about 0.1 to about 50 mg/kg body weight"). In addition, Van der Woning 2018 teaches that the doses can be administered "once weekly, once biweekly, once every three or four weeks, or once every other month" (page 47, paragraph 1, line 11-12). As evidentiary reference, ArgenX, 2022 discloses that the ARGX-115 has been renamed to ABBV-151 (page 1, "ARGX-115, now known as ABBV-151, was designed as a SIMPLE Antibody® inhibitor of GARP-TGF-β1 and is being investigated by AbbVie for the treatment of cancer. ARGX-115 is designed to block GARP and to reactive the immune system against tumors").
Therefore, it would have been obvious to the person of ordinary skill in the art to use the dosing strategy of livmoniplimab taught by Powderly et al., 2020 and Van der Woning 2018 to optimize the recommended phase II dosing as taught by Powderly to limit dose toxicity and expect reasonable success. The compound dosage in a composition is clearly a result effective parameter that a person having 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 obvious for an artisan of ordinary skill to determine the optimal amount of each ingredient, i.e., the dosage and dosing regimen, needed to achieve the desired results. 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," (see In re 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," (See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)).
In another aspect, Powderly does not teach that the cancer is a CMS4 enriched microsatellite stable colorectal cancer as recited in claim 1. Spallanzani et al. 2018 teaches that one strategy to treating CMS4 enriched microsatellite stable colorectal cancer is to target the TGF pathway and immune checkpoint inhibition (page10, Table 3, under Strategies for immunotherapy for CMS4). Further, Spallanzani et al., 2018 teach that the CMS4 tumors or mesenchymal CRC may have synergic effect of TGF-[Symbol font/0x62] and PD-1 inhibition (page 7, paragraph 1, "Preclinical data suggested a synergic effect of TGF-[Symbol font/0x62] and PD-1 inhibition in mouse model of mesenchymal CRC"). Therefore, it would have been obvious to combine livmoniplimab and budigalimab to treat CMS4 enriched microsatellite stable colorectal cancer to enhance anti-tumor effect of the treatment.
In another aspect, Powderly teach the method of treating cancers that are locally advanced and metastatic solid tumors (page 1, title) but does not teach that the locally advanced or metastatic solid tumors are microsatellite stable colorectal cancer (claim 3), non-small cell lung cancer (NSCLC) (claim 5), relapsed/refractory non-small cell lung cancer (NSCLC) (claim 8), pancreatic adenocarcinoma (claim 10), muscle invasive bladder cancer (claim 13), head and neck squamous cell carcinoma (claim 17), hepatocellular carcinoma (HCC) (claim 19) wherein the subject had no previous lines of treatment for HCC (claim 21), had one previous line of treatment for HCC (claim 22), and had more than one previous line of treatment for HCC (claim 23); and urothelial cancer (claim 24). NCT03821935, 2022 recites study participants in the method of treating locally advanced or metastatic solid tumors with livmoniplimab and budigalimab which include "pancreatic adenocarcinoma"; "urothelial cancer of the bladder and urinary tract"; "HCC and must have disease progression during or after 1 prior line of systemic therapy"; "HNSCC (arising from the oral cavity, oropharynx, hypopharynx, or larynx)"; "CRC participants with microsatellite stable or mismatch repair proficient colorectal adenocarcinoma"; and "histologically or cytologically confirmed advanced or metastatic NSCLC" (page 18-19, Inclusion Criteria). Further, NCT03821935, 2022 teaches that the study assesses the safety, pharmacokinetics (PK), and preliminary efficacy of ABBV-151 alone and in combination with budigalimab.
Therefore, it would have been obvious to include the locally advanced or metastatic solid tumors taught by NCT03821935, 2022 to assess the safety, pharmacokinetics and preliminary efficacy of livmoniplimab and budigalimab in treating the solid tumors that are disclosed by NCT03821935, 2022.
Regarding instant claims 2, 4, 7, 9, 11, 14, 16, 18, 20, and 25, Powderly et al., 2020 teach that targeting both TGF-[Symbol font/0x62]1 and programmed cell death has enhanced anti-tumor effects compared with anti-PD-1 alone (page 1, background, “Combining ABBV-151 with the anti-PD-1 mAb budigalimab (ABBV-181) may enable a more effective antitumor immune response by reducing the immunosuppressive effect of TGF[Symbol font/0x62]1”).
However, Powderly but does not teach the dosing of budigalimab. Italiano et al., 2022 teaches the doses of budigalimab (page 1, Abstract, Patients and Methods, “budigalimab was administered at 250 mg intravenously Q2W or 500 mg intravenously Q4W”). Italiano et al., 2022 further teaches that “budigalimab has a manageable safety profile with evidence of biologic and clinical activity in patients with previously treated HNSCC and NSCLC that seems to be similar to approved PD-1 inhibitors” (page 427, column 1-2, paragraph 5).
Therefore, it would have been obvious to the person of ordinary skill in the art to use the dosing of budigalimab that has a manageable safety profile and has clinical activity in cancer patients as taught by Italiano et al., 2022 and applied to the method of treating taught in Powderly et al., 2020.
Regarding instant claims 26 and 27, as described above and dependent on claim 19, Powderly et al., 2020 teaches the method of treating solid tumors including hepatocellular carcinoma (HCC) by administering livmoniplimab (claim 19) and budigalimab (claim 20) and teaches that preclinical data demonstrated that targeting both GARP-TGF[Symbol font/0x62]1 and programmed cell death protein 1 (PD-1) improved antitumor effects compared with anti-PD-1 alone (page 1, background).
With respect to claim 26, Van der Woning, 2018 teaches that the combination of the livmoniplimab and anti-PD1 antibodies can improve efficacy of cancer immunotherapies (page 4, line 5, "therapeutic agents capable of dampening this pathway may serve as useful tools to improve efficacy of cancer vaccines or other cancer immunotherapy strategies designed to harness the power of the body's immune system to treat cancer", page 47 line 28 - page 49, line 3 "suitable tumor antigens for use as tumor vaccines known in the art include[...] anti-PD-1 antibodies").
Claim 15 is rejected under 35 U.S.C. 103 as being unpatentable over Powderly et al., 2020 (cited previously); Van der Woning 2018 (cited previously); Italiano et al., 2021 (cited previously); and NCT03821935, 2022 (cited previously), and further in view of Muthukaruppan et al., 2018 (Muthukaruppan et al. 277P Investigation of the role of transforming growth factor beta in the development and progression of granulosa cell tumours of the ovary, Annals of Oncology, Volume 29, Issue suppl_9, November 2018, mdy436.024, https://doi.org/10.1093/annonc/mdy436.024).
As described above, while Powderly et al., 2020 teach the method of treating locally advanced or metastatic solid tumors with livmoniplimab and budigalimab, Powderly does not teach that the solid tumor is ovarian granulosa cell tumor (GCT) containing FOXL2 C134W mutation as recited in claim 15. Muthukaruppan et al., 2018 teaches that the GCT is a rare type of ovarian cancer and 97% of the adult GCT have the FOXL2 mutation. Muthukaruppan et al., 2018 also teaches that the TGF[Symbol font/0x62] signaling pathway is involved and that an TGF[Symbol font/0x62] inhibitor has an inhibitory effect on GCT (page 1, background and results). Therefore, it would have been obvious to the person of ordinary skill in the art to add GCT the cancers that can be treated in the method of treating as taught by Powderly et al., 2020 and NCT03821935, 2022 and expect reasonable success at inducing an inhibitory effect by blocking TGF[Symbol font/0x62] as taught by Muthukaruppan et al., 2018.
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Powderly et al., 2020 (cited previously); Van der Woning 2018 (cited previously); Italiano et al., 2021 (cited previously); and NCT03821935, 2022 (cited previously) as applied to claim 5 above, and further in view of Tomasini et al., 2016 (Tomasini et al. Pemetrexed for advanced stage nonsquamous non-small cell lung cancer: latest evidence about its extended use and outcomes. Ther Adv Med Oncol. 2016 May;8(3):198-208. doi: 10.1177/1758834016644155. Epub 2016 May 9).
While Powderly et al., 2020 and NCT03821935, 2022 teaches the method of treating non-small cell lung cancer with livmoniplimab and budigalimab and Van der Woning 2018 teaches livmoniplimab dosing and Italiano et al. 2021 teaches budigalimab dosing as described above, Powderly et al., 2020 does not teach the method further comprising administration of carboplatin and pemetrexed. Tomasini et al., 2016 teaches that pemetrexed is one of the recommended drugs combined with cisplatin or carboplatin for first-line treatment of NSCLC (page 198, column 2, paragraph 1) and because of the good efficacy and tolerability profile of pemetrexed, Tomasini discloses studies the combination of pemetrexed with immunotherapies (page 204, column 1, Perspectives). Therefore, it would have been obvious to the person of ordinary skill in the art to improve the method of treating NSCLC using the recommended and approved treatments for NSCLC using pemetrexed and carboplatin with livmoniplimab and budigalimab.
Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Powderly et al., 2020 (cited previously); Van der Woning 2018 (cited previously); Italiano et al., 2021 (cited previously); and NCT03821935, 2022 (cited previously) as applied to claim 10 above, and further in view of Thota et al., 2014 (Thota et al. Treatment of metastatic pancreatic adenocarcinoma: a review. Oncology (Williston Park). 2014 Jan;28(1):70-4. PMID: 24683721. https://www.cancernetwork.com/view/treatment-metastatic-pancreatic-adenocarcinoma-review).
Thota et al., 2014 teaches the method further comprising administration of paclitaxel or nab-paclitaxel and gemcitabine in treating pancreatic adenocarcinoma and that the combination has a synergistic effect (page 4, paragraph 5, “The synergistic effect of nab-paclitaxel and gemcitabine is attributable to several factors, including its favorable pharmacokinetic properties that enable delivery of a higher dose of paclitaxel, which not only is directly cytotoxic but also raises intratumoral gemcitabine accumulation through the depletion of the stromal matrix and increases in tumor microvasculature”). Thota et al., 2014 discloses that the paclitaxel or nab-paclitaxel and gemcitabine combination improves survival of pancreatic adenocarcinoma patients by only less than a year, so molecularly targeted therapies and immune mediators are proposed to improve treatment options (page 5, conclusions). Therefore, it would have been obvious to the person of ordinary skill in the art to include livmoniplimab and budigalimab in the method of treating pancreatic adenocarcinoma to enhance current treatment options using paclitaxel or nab-paclitaxel and gemcitabine.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Lam Thuy Vi Tran Ho whose telephone number is (571)272-9135. The examiner can normally be reached Monday-Friday 7:30-3.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Joanne Hama can be reached at (571) 272-2911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/LAM THUY VI TRAN HO/Examiner, Art Unit 1647 /L.T./Examiner, Art Unit 1647 /JOANNE HAMA/Supervisory Patent Examiner, Art Unit 1647