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 application claims priority to provisional applications 63/212781, filed on 21 June 2021, and 63/257879, filed on 20 October 2021, and is a 371 of PCT/EP2022/066764, filed on 20 June 2022. The effective filing date is 21 June 2021.
Information Disclosure Statement
The information disclosure statements (IDS) filed on 26 June 2026, 30 January 2026, 07 October 2025, 04 September 2025, 06 May 2025, and 16 January 2025 were considered by the examiner.
Status of Application, Amendments, and/or Claims
Claims 1-101 are the original claims. In the amendment of 02 August 2024, claims 2, 4, 7, 8, 11, 14, 16, 17, 19-21, 23, 24, 26-35, 37-43, 45,-47, 49-65, 67, 70, 72-75, 77-79, 81-85, 87, 88, and 90-101 were cancelled, and claims 1, 3, 5, 6, 9, 12, 15, 18, 22, 25, 36, 44, 48, 66, 68, 69, 71, 76, 80, 86, and 89 were amended. Claims 1, 3, 5, 6, 9, 10, 12, 13, 15, 18, 22, 25, 36, 44, 48, 66, 68, 69, 71, 76, 80, 86, and 89 are pending and the subject of this office action.
Claim Objections
Claim 68 is objected to because of the following informalities: When describing the amino acid sequences, corresponding to the CDRs of the second binding arm, the applicant references SEQ ID NOs: 18-20, 22, and 23. These sequences appear to correspond to constant regions and not the intended CDRs. The examiner has proceeded, under the assumption that these references were an unintended mistake, and has evaluated the claim using the SEQ ID Nos, recited in other claims (SEQ ID Nos: 9-11, 13, and 14), that also refer to these CDRS. Appropriate correction is required.
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.
Claim 80 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 80 recites “preferably.” It is unclear whether “a PD-L1 positive tumor” is encompassed by the claim or not. See MPEP2173.05(d).
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 25 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claim is drawn to a method, comprising the administration of a bispecific anti-CD137/PD-L1 antibody. Claim 25 establishes that the antigen binding regions specific for CD137 share at least 90 % sequence identity to SEQ ID Nos: 1 (heavy chain) and 5 (light chain), and that the antigen binding regions specific for PD-L1 share at least 90 % sequence identity to SEQ ID Nos: 8 (heavy chain) and 12 (light chain). The claims encompass a genus of heavy and light chain variable regions comprising up to 10% variability (≤ 90% identity) in both the heavy and light chain variable regions, which are claimed to specifically bind to either CD137 or PD-L1.
The instant disclosure, however, does not provide an adequate number of species of the claimed genus nor does the disclosure provide a structure-function correlation that would allow for an ordinarily skilled artisan to envision what variation can occur in the heavy and light chains, particularly in the CDR regions, such that the obtained structure would result in the claimed functions.
The current disclosure discusses methods for treating cancer, comprising the administration of a bispecific antibody, that comprises antigen binding domains, comprising CDRs defined by SEQ ID Nos: 2-4 (heavy chain) and SEQ ID Nos: 6 and 7, and a CDR2 (GAS) (light chain) or SEQ ID Nos: 9-11 (heavy chain) and SEQ ID Nos: 13 and 14, and a CDR2 (DDN) (light chain). These antigen binding domains, with 100% sequence identity in the CDR regions of the heavy and light chain variable regions (encompassed in SEQ ID Nos: 1, 5, 8, 12, 36-39) represents the binding domains that applicant was in possession of at the time of filing. It is noted that there would be support for antibodies sharing 100% identity of the full complement of the six CDRs together with some percentages of identity in the framework region or regions not affecting antigen binding that would have been predictable.
The state of the art around the effective filing date of the claimed invention also does not provide an adequate number of species of the claimed genus or the necessary structure-function correlation. Rather, the art demonstrates that antibody functionality was known to depend on the entire antibody structure, particularly a full complement of six CDRs. Chiu ML, et al. (2019) Antibody Structure and Function: The Basis for Engineering Therapeutics. Antibodies (Basel). Dec 3;8(4):55 teaches that the antigen-binding site of immunoglobulins is formed by the pairing of the variable domains (VH and VL) of the Fab region. Chiu teaches that each domain contributes three complementarity determining regions (CDRs), specifically, three from the VL and three from the VH, and that the six CDR loops are in proximity to each other resulting from the orientation of the VL and VH regions. Chiu teaches that the configuration of the VL and VH brings the three CDRs of the VL and VH domains together to form the antigen-binding site (page 4, paragraph 2). Here, Chiu teaches that the interaction between the heavy and light chain variable domains affects the conformation of the binding region of the antibody and therefore the antibody’s ability to bind to its target. Furthermore, the teachings of Chiu point out that the binding site is formed by the combination of the heavy and light chain CDRs (six regions) together. Based on these teachings, an ordinarily skilled artisan would not have been able to predictably determine which amino acids in which CDR regions could be modified such that the antigen binding domain would still perform the function of binding CD137 or PD-L1.
Rabia L, et al. (2018) Understanding and overcoming tradeoffs between antibody affinity, specificity, stability, and solubility. Biochem Eng. J. 15(137); 365-374 discusses the challenges with optimizing antibody properties and states “the most important antibody properties relate to their natural functions, such as their high binding affinity and specificity mediated by their complementarity-determining regions (CDRs) within the variable regions... Other key natural antibody properties include their effector functions — such as antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC)- which are mediated by their constant regions” (page 2, paragraph 1). Rabia further teaches that “most antibodies identified during the initial discovery process are not suitable for therapeutic use and require additional optimization. For example, the binding affinities of some lead antibodies are not high enough for therapeutic applications” (page 2, paragraph 3). Rabia goes on to state that “natural antibody affinity maturation relies on the introduction of somatic mutations followed by clonal selection of antibody variants with improved affinity. However, not all somatic mutations contribute to antibody affinity...antibodies accumulate some somatic mutations to increase affinity and others to compensate for the destabilizing effects of affinity-enhancing mutations” (page 2, paragraph 4). Rabia further provides an example of researchers who introduced mutations throughout variable frameworks and CDRs and created libraries to sort antibody variants with high antigen binding. In this case an antibody was identified that displayed increased affinity but had a significant reduction in stability (page 3, paragraph 2). Rabia concludes by stating that “a final key area of future work is the development of improved computational methods for predicting mutations in antibody CDRs and frameworks that co-optimize multiple antibody properties” and that “future efforts will also need to improve structural predictions of antibody CDRs — especially the long and highly variable heavy chain CDR3-to accurately predict CDR mutations that are beneficial to different antibody properties” (page 9, paragraph 4 — page 10 paragraph 2).
Based on the teachings of Rabia, introducing mutations in antibody structure, particularly in the CDR regions, is not predictable and requires experimentation following mutation to ensure that binding affinity is maintained and a stable antibody is created. Rabia further spoke to the use of libraries and computational methods for predicting and co-optimizing antibody properties and demonstrated how these methods are not robust enough yet to yield predictable results. This teaching demonstrates that modifications to the sequences of the claimed invention could result in antigen binding domains that are not suitable for their intended role of binding CD137 and PD-L1.
Overall, it is not evident from the disclosure, or the prior art, that applicant was in possession of a representative number of species of the claimed genus at the time of filing. Specifically, it is not evident that applicant was in possession of a representative number of antigen binding domains with variation in the CDRs, which are the known binding regions of the antibody/antigen binding domain, that performed the claimed function. Additionally, there is no disclosed or art recognized relationship between antibody structure/antigen binding region and function which would allow for the predictable modification of the claimed antigen binding domain with up to 10% variance anywhere in the structure, particularly in the CDRs, while maintaining the claimed functions. Therefore, the instant claims are found to not meet the written description requirement.
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, 2, 5, 6, 9, 10, 12, 13, 15, 18, 22, 25, 36, 44, 48, 66, 68, 69, 71, 76, and 80 are rejected under 35 U.S.C. 103 as being unpatentable over WO2019025545 (herein Altintas).
In regard to claim 1, Altintas relates to anti-PD-L1/CD137 bispecific antibodies and their use in medicine (Abstract). The authors teach that these antibodies comprise one binding region specific for CD137, also known as 4-1BB, and one binding region specific for PD-L1 (Page 3 lines 14-18). It is stated that by binding these targets on T cells the antibody is able to stimulate an activation receptor, via CD137 binding, and block inhibitory signaling, via PD-L1 binding, resulting in enhanced T cell proliferation, activation, and survival (Page 4 lines 3-7). The authors teach methods, comprising intravenous administration of these antibodies (Relevant to instant claim 18), in a pharmaceutical composition, to patients, afflicted with PD-L1-related diseases (Page 79 lines 3-21). It is taught that PD-L1-related diseases may include cancer diseases, characterized by the presence of solid tumors (Relevant to instant claim 80) (Page 80 lines 24-30). Furthermore, the authors teach that this method may inhibit growth of one or more tumor cells expressing PD-L1 and induce killing of tumor cells expressing PD-L1 (Page 81 lines 11-15).
In regard to the structure of the bispecific CD137/PD-L1 antibodies, Altintas teaches variable heavy and light chains comprising amino acid sequences sharing 100% sequence identity with those corresponding to SEQ ID NO: 1 and 5 (anti-CD137) and SEQ ID NO: 8 and 12 (anti-PD-L1), as shown in the sequence alignments below (Relevant to instant claims 22, 25, 66, 68, and 69).
Anti-CD137 Variable Heavy:
Refence SEQ ID NO:15 EVQLVESGGGLVQPGRSLRLSCTASGFSLNDYWMSWVRQAPGKGLEWVGYIDVGGSLYYA 60
Instant SEQ ID NO:1 EVQLVESGGGLVQPGRSLRLSCTASGFSLNDYWMSWVRQAPGKGLEWVGYIDVGGSLYYA 60
************************************************************
Refence SEQ ID NO:15 ASVKGRFTISRDDSKSIAYLQMNSLKTEDTAVYYCARGGLTYGFDLWGQGTLVTVSS 117
Instant SEQ ID NO:1 ASVKGRFTISRDDSKSIAYLQMNSLKTEDTAVYYCARGGLTYGFDLWGQGTLVTVSS 117
*********************************************************
Anti-CD137 Variable Light:
Refence SEQ ID NO:16 DIVMTQSPSSLSASVGDRVTITCQASEDISSYLAWYQQKPGKAPKRLIYGASDLASGVPS 60
Instant SEQ ID NO:5 DIVMTQSPSSLSASVGDRVTITCQASEDISSYLAWYQQKPGKAPKRLIYGASDLASGVPS 60
************************************************************
Refence SEQ ID NO:16 RFSASGSGTDYTFTISSLQPEDIATYYCHYYATISGLGVAFGGGTKVEIK 110
Instant SEQ ID NO:5 RFSASGSGTDYTFTISSLQPEDIATYYCHYYATISGLGVAFGGGTKVEIK 110
**************************************************
Anti-PD-L1 Variable Heavy:
Refence SEQ ID NO:17 EVQLLEPGGGLVQPGGSLRLSCEASGSTFSTYAMSWVRQAPGKGLEWVSGFSGSGGFTFY 60
Instant SEQ ID NO:8 EVQLLEPGGGLVQPGGSLRLSCEASGSTFSTYAMSWVRQAPGKGLEWVSGFSGSGGFTFY 60
************************************************************
Refence SEQ ID NO:17 ADSVRGRFTISRDSSKNTLFLQMSSLRAEDTAVYYCAIPARGYNYGSFQHWGQGTLVTVS 120
Instant SEQ ID NO:8 ADSVRGRFTISRDSSKNTLFLQMSSLRAEDTAVYYCAIPARGYNYGSFQHWGQGTLVTVS 120
************************************************************
Refence SEQ ID NO:17 S 121
Instant SEQ ID NO:8 S 121
*
Anti-PD-L1 Variable Light:
Refence SEQ ID NO:21 SYVLTQPPSVSVAPGQTARITCGGNNIGSKSVHWYQQKPGQAPVLVVYDDNDRPSGLPER 60
Instant SEQ ID NO:12 SYVLTQPPSVSVAPGQTARITCGGNNIGSKSVHWYQQKPGQAPVLVVYDDNDRPSGLPER 60
************************************************************
Refence SEQ ID NO:21 FSGSNSGNTATLTISRVEAGDEADYYCQVWDSSSDHVVFGGGTKLTVL 108
Instant SEQ ID NO:12 FSGSNSGNTATLTISRVEAGDEADYYCQVWDSSSDHVVFGGGTKLTVL 108
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In addition, it is taught that the variable regions discussed above were cloned into IgG1 expression vectors (comprising the lambda constant region for anti-PD-L1 or kappa for anti-CD137), in which mutations within the IgG1 heavy, L234F, L235E, D265A, and F405L within the anti-CD137 vector or L234F, L235E, D265A and K409R within the anti-PD-L1 vector, allowed for subsequent generation of bispecific antibodies by 2-MEA-induced Fab-arm exchange (Relevant to instant claims 36, 44, 48, 66, 68, and 69) (Page 92-Page 93 line 5 and Page 89 line 4- Page 90 line 16). By combining these teachings with those regarding the variable region amino acid sequences, described above, one would arrive at antibody sequences corresponding to those referenced in instant claim 71, as illustrated by the following alignments, in which the variable regions are shown in red:
Anti-CD137 Heavy Chain:
Instant SEQ ID NO:36 EVQLVESGGGLVQPGRSLRLSCTASGFSLNDYWMSWVRQAPGKGLEWVGYIDVGGSLYYA 60
Refence SEQ ID NO:25 ------------------------------------------------------------ 0
Instant SEQ ID NO:36 ASVKGRFTISRDDSKSIAYLQMNSLKTEDTAVYYCARGGLTYGFDLWGQGTLVTVSSAST 120
Refence SEQ ID NO:25 ---------------------------------------------------------AST 3
***
Instant SEQ ID NO:36 KGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY 180
Refence SEQ ID NO:25 KGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY 63
************************************************************
Instant SEQ ID NO:36 SLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEFEGGPSV 240
Refence SEQ ID NO:25 SLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEFEGGPSV 123
************************************************************
Instant SEQ ID NO:36 FLFPPKPKDTLMISRTPEVTCVVVAVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY 300
Refence SEQ ID NO:25 FLFPPKPKDTLMISRTPEVTCVVVAVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY 183
************************************************************
Instant SEQ ID NO:36 RVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTK 360
Refence SEQ ID NO:25 RVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTK 243
************************************************************
Instant SEQ ID NO:36 NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQQG 420
Refence SEQ ID NO:25 NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQQG 303
************************************************************
Instant SEQ ID NO:36 NVFSCSVMHEALHNHYTQKSLSLSPG- 446
Refence SEQ ID NO:25 NVFSCSVMHEALHNHYTQKSLSLSPGK 330
**************************
Anti-CD137 Light Chain:
Instant SEQ ID NO:37 DIVMTQSPSSLSASVGDRVTITCQASEDISSYLAWYQQKPGKAPKRLIYGASDLASGVPS 60
Refence SEQ ID NO:26 ------------------------------------------------------------ 0
Instant SEQ ID NO:37 RFSASGSGTDYTFTISSLQPEDIATYYCHYYATISGLGVAFGGGTKVEIKRTVAAPSVFI 120
Refence SEQ ID NO:26 --------------------------------------------------RTVAAPSVFI 10
**********
Instant SEQ ID NO:37 FPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSS 180
Refence SEQ ID NO:26 FPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSS 70
************************************************************
Instant SEQ ID NO:37 TLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 217
Refence SEQ ID NO:26 TLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 107
*************************************
Anti-PD-L1 Heavy Chain:
Instant SEQ ID NO:36 EVQLLEPGGGLVQPGGSLRLSCEASGSTFSTYAMSWVRQAPGKGLEWVSGFSGSGGFTFY 60
Refence SEQ ID NO:24 ------------------------------------------------------------ 0
Instant SEQ ID NO:36 ADSVRGRFTISRDSSKNTLFLQMSSLRAEDTAVYYCAIPARGYNYGSFQHWGQGTLVTVS 120
Refence SEQ ID NO:24 ------------------------------------------------------------ 0
Instant SEQ ID NO:36 SASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQS 180
Refence SEQ ID NO:24 -ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQS 59
***********************************************************
Instant SEQ ID NO:36 SGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEFEG 240
Refence SEQ ID NO:24 SGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEFEG 119
************************************************************
Instant SEQ ID NO:36 GPSVFLFPPKPKDTLMISRTPEVTCVVVAVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY 300
Refence SEQ ID NO:24 GPSVFLFPPKPKDTLMISRTPEVTCVVVAVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY 179
************************************************************
Instant SEQ ID NO:36 NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE 360
Refence SEQ ID NO:24 NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE 239
************************************************************
Instant SEQ ID NO:36 EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFLLYSKLTVDKSR 420
Refence SEQ ID NO:24 EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFLLYSKLTVDKSR 299
************************************************************
Instant SEQ ID NO:36 WQQGNVFSCSVMHEALHNHYTQKSLSLSPG- 450
Refence SEQ ID NO:24 WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 330
******************************
Anti-PD-L1 Light Chain:
Instant SEQ ID NO:39 SYVLTQPPSVSVAPGQTARITCGGNNIGSKSVHWYQQKPGQAPVLVVYDDNDRPSGLPER 60
Refence SEQ ID NO:27 ------------------------------------------------------------ 0
Instant SEQ ID NO:39 FSGSNSGNTATLTISRVEAGDEADYYCQVWDSSSDHVVFGGGTKLTVLGQPKAAPSVTLF 120
Refence SEQ ID NO:27 ------------------------------------------------GQPKAAPSVTLF 12
************
Instant SEQ ID NO:39 PPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYL 180
Refence SEQ ID NO:27 PPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYL 72
************************************************************
Instant SEQ ID NO:39 SLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS 214
Refence SEQ ID NO:27 SLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS 106
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In regard to dosing regimens (i.e. specific dose amount, the route of administration, the frequency or time interval between doses, and the total duration of treatment needed to safely achieve and maintain the desired therapeutic effect), the authors teach a therapeutically effective dose range of 0.1-100 mg/kg, and state that “The efficient dosages and the dosage regimens for the binding agent depend on the disease or condition to be treated and may be determined by the persons skilled in the art” (Page 81 lines 28 – Page 82 line 2). This dose range encompasses the amounts defined for Dose A and Dose B in claim 1 (as well as claims 3 and 5). In addition to teaching dose ranges encompassing those of claim 1 and suggesting optimization, Altintas also provides guidance, regarding selecting suitable dose amount, and defines this dose amount as “the lowest effective dose to produce a therapeutic effect” (Page 82 lines 8-10). Additionally, it is taught that treatment may initiate with lower dose amounts and that the dose amount may be increased, further into the treatment, to achieve the desired effect, which relates to the increased amount of binding agent in Dose B, relative to Dose A of claim 1 (Page 82 lines 3-8).
Altintas also discloses the results of an anti-tumor efficacy study, performed in mice, comprising the administration of a surrogate mouse bispecific anti-CD137/PD-L1 antibody, mCD137-3H3xmPD-L1-MPDL3280A (Page 100 line 24- Page 102 line 5 and Figure 12). In this study 20μg of the surrogate antibody was administered, intraperitoneally, to female BALB/c mice bearing subcutaneous CT26 tumors, using a schedule of every 2-3 days for the first eight injection and every seven days for the remainder of injections. When compared to control animals, mice receiving the anti-CD137/PD-L1 antibody had the most efficiently controlled tumor growth, with 50% of the treated mice going into complete tumor regression (Figure 12). It is noted that the mice used for in this study weighed between 17-24 g, and when using the midpoint of this range, 20.5g, one can deduce that the administered dose was ~0.98 mg/kg. This administered dose overlaps with claimed Dose A range of claim 1
Altintas teaches the antibodies of the instant invention for the treatment of cancer as well as dose ranges that overlap those claimed. This demonstrates that the prior art was aware of bispecific anti-CD137/PD-L1 antibody dosing regimens that are effective in the treatment of cancer. Finding the optimal dosing regimen for a patient is considered to be routine optimization when general guidelines and considerations for administration were known in the prior art.
MPEP 2144.05 (II) speaks to Routine Optimization stating that "’[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 "It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions."). See also KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007)”. It would have been obvious for a person of ordinary skill in the art prior to the effective filing date of the claimed invention to have used the dosages taught by Altintas as a starting point for routine experimentation to optimize the dosage for treatment.
In this case, it would have been obvious for a person of ordinary skill in the art prior to the effective filing date of the claimed invention to have used the dosages taught by Altintas as a starting point for routine experimentation. As Altintas additionally teaches that a dosing schedule may initiate with lower dose amounts and that the dose amount may be increased, further into the treatment, an ordinarily skilled artisan would have reasonably arrived at the instantly claimed invention via routine optimization (Relevant to instant claims 1, 3, 5, 6, 9, 10, 12, 13, 15, 18, and 76).
Claims 86 and 89 are rejected under 35 U.S.C. 103 as being unpatentable over WO2019025545 (herein Altintas) in view of Woroniecka KI, et al. (2020) 4-1BB Agonism Averts TIL Exhaustion and Licenses PD-1 Blockade in Glioblastoma and Other Intracranial Cancers. Clin Cancer Res. 2020 Mar 15;26(6):1349-1358 (herein Woroniecka).
In regard to claims 86 and 89, Altintas teaches a method of treating cancer, comprising the administration of a bispecific anti-CD137/PD-L1 antibody, as discussed for the 35 U.S.C. 103 rejections of claims 1, 2, 5, 6, 9, 10, 12, 13, 15, 18, 22, 25, 36, 44, 48, 66, 68, 69, 71, 76, and 80.
Altintas does not teach the use of a bispecific antibody for the treatment of a relapsed or refractory cancer, wherein the subject has received at least one prior treatment regimen. Woroniecka teaches this deficiency.
Woroniecka et al relates to the development of strategies to avert T-cell exhaustion brought on checkpoint blockade therapy for the treatment of glioblastoma (Abstract). It is taught that checkpoint blockade has demonstrated limited success in the treatment of glioblastoma, in large part due to T cell disfunction with insufficient T cell activation to perpetuate with therapy (Introduction). It is stated that “checkpoint blockade is dependent upon the availability of functional, activated T cells for its effectiveness, an amenity not afforded amongst dysfunctional, exhausted GBM TIL with poor tumor infiltration” (Discussion). The authors also teach that non-exhausted tumor-infiltrating lymphocytes disproportionately express 4-1BB/CD137, and that 4-1BB/CD137 agonism improves their function and averts exhaustion (Introduction). The authors go on to show that 4-1BB agonism synergizes with the blockading of the PD-1/PD-L1 axis in multiple cancer models, that are normally resistant to checkpoint blockade therapy (Introduction and Results: Enhancing 4-1BB levels on CD8+ T cells is sufficient to proffer an effective response to 4-1BB agonism and PD-1 blockade).
Considering the teachings of Woroniecka, it would have been obvious to one skilled in the art to apply the method of treating cancer, taught by Altintas, to patients with cancers that have relapsed or are refractory to previous therapies, comprising checkpoint blockade. As taught by Woroniecka, checkpoint blockade therapy requires sufficient levels of T cell activation to be effective, which is likely not the case in patient with checkpoint blockade refractory or relapsed forms of cancer (Introduction). By applying the method of Altintas, which comprises an agonistic anti-CD137 antibody, one would effectively be improving the function of activated non-exhausted T cells, while simultaneously averting exhaustion, thus exploiting the synergistic effect described by Woroniecka. Furthermore, based on the examples provided by Woroniecka, there would be a reasonable expectation of success, as several of the models tested by Woroniecka are known to be resistant to checkpoint blockade.
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, 2, 5, 6, 9, 10, 12, 13, 15, 18, 22, 25, 36, 44, 48, 66, 68, 69, 71, 76, 80, 86, and 89 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 35, 37, 54, 55, 61, 63, 101, 103-106 of U.S. Patent No. 10968280 in view of WO2019025545 (herein Altintas) and Woroniecka KI, et al. (2020) 4-1BB Agonism Averts TIL Exhaustion and Licenses PD-1 Blockade in Glioblastoma and Other Intracranial Cancers. Clin Cancer Res. 2020 Mar 15;26(6):1349-1358 (herein Woroniecka).
Patented claim 1 recites a multispecific antibody comprising a first antigen-binding region capable of binding to human CD137 and a second antigen-binding region capable of binding to human PD-L1, wherein the second antigen-binding region inhibits the binding of human PD-L1 to human PD-L1, wherein (i) the first antigen-binding region comprises a first heavy chain variable region (VH) and a first light chain variable region (VL), wherein the first VH comprises the amino acid sequence as set forth in SEQ ID NO: 15, . . . and (ii) the second antigen-binding region comprises a second heavy chain variable region (VH) and a second light chain variable region (VL), wherein the second VH comprises the amino acid sequence as set forth in SEQ ID NO: 17, . . .
Patented claim 2 recites that the multispecific antibody of claim 1, wherein (i) the first VL comprises the amino acid sequence as set forth in SEQ ID NO: 16; and (ii) the second VL comprises the amino acid sequence as set forth in SEQ ID NO: 21.
Patented SEQ ID NO: 15 discloses the anti-CD137 CDRs of present SEQ ID NOs: 2 – 4; patented SEQ ID NO: 16 discloses the anti-CD137 CDRs of present 6, 7, and the sequence GAS; patented SEQ ID NO: 17 discloses the anti-PD-L1 CDRs of present SEQ ID NOs: 9-11; and patented SEQ ID NO: 21 discloses the anti-PD-L1 CDRs of present SEQ ID NOs: 13, 14, and the sequence DDN of the present claims.
The referenced claims describe a multi-specific antibody identical to the binding agent of the current application. The main difference between the present claims and the patented claims is that the present claims recite a method for reducing or preventing progression of a tumor or treating cancer by administering the binding agent. However, Altintas discloses this difference, as discussed in the 35 U.S.C. 103 rejection section of the current office action. Briefly, Altintas teaches methods for treating cancer, comprising the administration of a bispecific anti-CD137/PD-L1 antibody, of an identical structure to that disclosed in referenced patent and the current application.
Because the patented claims recite a multispecific antibody comprising a first antigen-binding region capable of binding to human CD137 and a second antigen-binding region capable of binding to human PD-L1, and Altintas teaches a method of cancer treatment that includes the multispecific antibody, it would have been obvious to one having ordinary skill in the art to use the patented multispecific antibody in the method of the present claims.
Claims 1, 2, 5, 6, 9, 10, 12, 13, 15, 18, 22, 25, 36, 44, 48, 66, 68, 69, 71, 76, 80, 86, and 89 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 8, 12, 15, 34, 35, 54, 55, 61, 63, and 89-98 of U.S. Patent No. 11459395 in view of WO2019025545 (herein Altintas) and Woroniecka KI, et al. (2020) 4-1BB Agonism Averts TIL Exhaustion and Licenses PD-1 Blockade in Glioblastoma and Other Intracranial Cancers. Clin Cancer Res. 2020 Mar 15;26(6):1349-1358 (herein Woroniecka).
Patented claim 8 recites a bispecific antibody, wherein the first arm comprises an antigen-binding region capable of binding to human CD137, and a second arm comprising an antigen-binding region capable of binding to human PD-L1. The anti PD-L1 antigen binding region comprises CDRs set forth in SEQ ID Nos: 18-20, 22, 23 and DDN.
Patented claim 35 recites a bispecific antibody, wherein the first arm comprises an antigen-binding region capable of binding to human CD137, and a second arm comprising an antigen-binding region capable of binding to human PD-L1. The anti-PD-L1 antigen binding region comprises CDRs set forth in SEQ ID Nos: 18-20, 22, 23 and DDN. The anti-CD137 antigen binding region comprises CDRs set forth in SEQ ID Nos: 9-11, 13, 14, and GAS.
Patented SEQ ID NOs: 9-11 discloses the anti-CD137 CDRs of present SEQ ID NOs: 2-4; patented SEQ ID NOs: 13, 14 discloses the anti-CD137 CDRs of present 6, 7, and the sequence GAS; patented SEQ ID NOs: 18-20 discloses the anti-PD-L1 CDRs of present SEQ ID NOs: 9-11; and patented SEQ ID NOs: 22 and 23 discloses the anti-PD-L1 CDRs of present SEQ ID NOs: 13 and 14 of the present claims.
The referenced claims describe a bispecific antibody identical to the binding agent of the current application. The main difference between the present claims and the patented claims is that the present claims recite a method for reducing or preventing progression of a tumor or treating cancer by administering the binding agent. However, Altintas discloses this difference, as discussed in the 35 U.S.C. 103 rejection section of the current office action. Briefly, Altintas teaches methods for treating cancer, comprising the administration of a bispecific anti-CD137/PD-L1 antibody, of an identical structure to that disclosed in referenced patent and the current application.
Because the patented claims recite a multispecific antibody comprising a first antigen-binding region capable of binding to human CD137 and a second antigen-binding region capable of binding to human PD-L1, and Altintas teaches a method of cancer treatment that includes the multispecific antibody, it would have been obvious to one having ordinary skill in the art to use the patented multispecific antibody in the method of the present claims.
Claims 1, 2, 5, 6, 9, 10, 12, 13, 15, 18, 22, 25, 36, 44, 48, 66, 68, 69, 71, 76, 80, 86, and 89 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 97, 98, 100-103, and 105-125 of co-pending U.S. Patent Application No. 17/289602 in view of WO2019025545 (herein Altintas) and Woroniecka KI, et al. (2020) 4-1BB Agonism Averts TIL Exhaustion and Licenses PD-1 Blockade in Glioblastoma and Other Intracranial Cancers. Clin Cancer Res. 2020 Mar 15;26(6):1349-1358 (herein Woroniecka).
Co-pending claim 97 recites a pharmaceutical formulation comprising: a) a multispecific antibody comprising a first binding arm capable of binding to human CD137 and a second binding arm capable of binding to human PD-L1, wherein the first binding arm comprises an antigen biding region comprising a first heavy chain variable region (VH) comprising an amino acid sequence of SEQ ID NO: 15; and a first light chain variable region (VL) comprising an amino acid sequence of SEQ ID NO: 16, and the second antigen-binding region comprises a second VH comprising an amino acid sequence of SEQ ID NO: 17; and a second (VL) comprising an amino acid sequence of SEQ ID NO: 21.
Co-pending SEQ ID NO: 15 discloses the anti-CD137 CDRs of present SEQ ID NOs: 2 – 4; co-pending SEQ ID NO: 16 discloses the anti-CD137 CDRs of present SEQ ID NOs: 6, 7, and the sequence GAS; co-pending SEQ ID NO: 17 discloses the anti-PD-L1 CDRs of present SEQ ID NOs: 9 – 11; and co-pending SEQ ID NO: 21 discloses the anti-PD-L1 CDRs of present SEQ ID NOs: 13, 14, and the sequence DDN of the present claims.
The referenced claims describe a pharmaceutical formulation comprising multi-specific antibody identical to the binding agent of the current application. The main difference between the present claims and the co-pending claims is that the present claims recite a method for reducing or preventing progression of a tumor or treating cancer by administering the binding agent. However, Altintas discloses this difference, as discussed in the 35 U.S.C. 103 rejection section of the current office action. Briefly, Altintas teaches methods for treating cancer, comprising the administration of a formulation comprising a bispecific anti-CD137/PD-L1 antibody, of an identical structure to that disclosed in referenced patent and the current application.
Because the co-pending claims recite a pharmaceutical composition comprising a multispecific antibody, comprising a first antigen-binding region capable of binding to human CD137 and a second antigen-binding region capable of binding to human PD-L1, and Altintas teaches a method of cancer treatment that includes the administration of a formulation comprising multispecific antibody, it would have been obvious to one having ordinary skill in the art to use the patented multispecific antibody in the method of the present claims.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 2, 5, 6, 9, 10, 12, 13, 15, 18, 22, 25, 36, 44, 48, 66, 68, 69, 71, 76, 80, 86, and 89 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 9, 22, 113-159 of U.S. Patent Application No. 17/795318 in view of WO2019025545 (herein Altintas) and Woroniecka KI, et al. (2020) 4-1BB Agonism Averts TIL Exhaustion and Licenses PD-1 Blockade in Glioblastoma and Other Intracranial Cancers. Clin Cancer Res. 2020 Mar 15;26(6):1349-1358 (herein Woroniecka).
Although the claims at issue are not identical, they are not patentably distinct from each other, because co-pending claim 9 recites a method for reducing progression of a tumor or for a method of treating cancer in a human subject, comprising administering, in at least one cyce, a multispecific antibody, comprising a first antigen-binding region capable of binding to human CD137, and a second antigen-binding region capable of binding to human PD-L1. It is also recited that the first binding region comprises a heavy chain variable region (VH) comprising an amino acid sequence of SEQ ID NO: 1 and a light chain variable region (VL) region comprising an amino acid sequence of ID NO: 5; and b) the second binding region comprises a heavy chain variable region (VH) comprising an amino acid sequence of SEQ ID NO: 8 and a light chain variable region (VL) region comprising an amino acid sequence of SEQ ID NO: 12. Additionally, co-pending claim 9 recites a dosage range of 0.3-5 mg/kg, which overlaps with both Dose A and Dose B of instant claim 1.
Co-pending SEQ ID NO: 1 discloses the anti-CD137 CDRs of present SEQ ID NOs: 2 – 4; co-pending SEQ ID NO: 5 discloses the anti-CD137 CDRs of present 6, 7, and the sequence GAS; co-pending SEQ ID NO: 8 discloses the anti-PD-L1 CDRs of present SEQ ID NOs: 9-11; and co-pending SEQ ID NO: 12 discloses the anti-PD-L1 CDRs of present SEQ ID NOs: 13, 14, and the sequence DDN of the present claims.
Co-pending claim 62 recites that the subject has received prior treatment with checkpoint inhibitor(s), such as agent(s) targeting PD-1/PD-L, such as a PD-1/PD-L1 inhibitor.
Thus, the present claims are rendered obvious by the co-pending claims, as they establish overlapping claim limitations and describe essentially the same invention.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 2, 5, 6, 9, 10, 12, 13, 15, 18, 22, 25, 36, 44, 48, 66, 68, 69, 71, 76, 80, 86, and 89 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 13, 20, 28, 32, 50, 51, 53, 57, 60, 62, 63, 64, 68, 70, 85, 99, 116 of U.S. Patent Application No. 18/038818 in view of WO2019025545 (herein Altintas) and Woroniecka KI, et al. (2020) 4-1BB Agonism Averts TIL Exhaustion and Licenses PD-1 Blockade in Glioblastoma and Other Intracranial Cancers. Clin Cancer Res. 2020 Mar 15;26(6):1349-1358 (herein Woroniecka).
Co-pending claim 1 recites a method for reducing or preventing progression of a tumor or treating cancer in a subject, comprising administering to the subject combined treatment with i} a binding agent comprising a first binding region binding to human CD137, and a second binding region binding to human PD-Li; and ii) a taxane chemotherapeutic agent. Additionally, the claim establishes that multispecific antibody comprises a) first binding region comprises a heavy chain variable region (VH) comprising the CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NO: 2, 3, and 4, respectively, and a light chain variable region (VL) comprising the CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NO: 6, GAS, 7, respectively; and b) the second antigen-binding region comprises a heavy chain variable region (VH) comprising the CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NO: 9, 10, 11 respectively, and a light chain variable region (VL) comprising the CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NO: 13, DDN, 14, respectively.
The CDRs of co-pending claim 6 are identical to the CDRs of claims 22, 25, 66, 68 and 71.
The referenced claims describe a method for treating cancer, comprising the administration of multi-specific antibody, identical to the binding agent of the current application, as well as a taxane chemotherapeutic agent. The main difference between the present claims and the co-pending claims is that the present claims are silent regarding the co-administration of a taxane chemotherapeutic agent. However, the claims of the referenced co-pending application encompass the limitations established in the current application.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 2, 5, 6, 9, 10, 12, 13, 15, 18, 22, 25, 36, 44, 48, 66, 68, 69, 71, 76, 80, 86, and 89 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-65 of U.S. Patent Application No. 18/698354 in view of WO2019025545 (herein Altintas) and Woroniecka KI, et al. (2020) 4-1BB Agonism Averts TIL Exhaustion and Licenses PD-1 Blockade in Glioblastoma and Other Intracranial Cancers. Clin Cancer Res. 2020 Mar 15;26(6):1349-1358 (herein Woroniecka).
Co-pending claim 1 recites a method for reducing or preventing the progression of a tumor or treating cancer in a subject, comprising administration of a binding agent prior to, simultaneously with, or after the administration of an anti-PD-1 antibody or fragment thereof. With the binding agent being defined as comprising a first region binding to CD137 and a second region that binds to PD-L1, wherein the first binding region of the binding agent comprises a heavy chain variable region (VH) comprising the amino acid sequence set forth in SEQ ID NO: 1 and a light chain variable region (VL) region comprising the amino acid sequence set forth in SEQ ID NO: 5; and b) the second binding region of the binding agent comprises a heavy chain variable region (VH) comprising the amino acid sequence set forth in SEQ ID NO: 11 and a light chain variable region (VL) region comprising the amino acid sequence set forth in SEQ ID NO:15.
Co-pending SEQ ID NO: 1 discloses the anti-CD137 CDRs of present SEQ ID NOs: 2-4; co-pending SEQ ID NO: 5 discloses the anti-CD137 CDRs of present SEQ ID NOs: 6, 7, and the sequence GAS; co-pending SEQ ID NO: 11 discloses the anti-PD-L1 CDRs of present SEQ ID NOs: 9-11; and co-pending SEQ ID NO: 15 discloses the anti-PD-L1 CDRs of present SEQ ID NOs: 13, 14, and the sequence DDN of the present claims.
The referenced claims describe a method for treating cancer, comprising the administration of multi-specific antibody, identical to the binding agent of the current application, as well as an anti-PD-1 antibody or fragment thereof. The main difference between the present claims and the co-pending claims is that the present claims are silent regarding the additional administration of an anti-PD-1 antibody or fragment thereof. However, the claims of the referenced co-pending application encompass the limitations established in the current application.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 2, 5, 6, 9, 10, 12, 13, 15, 18, 22, 25, 36, 44, 48, 66, 68, 69, 71, 76, 80, 86, and 89 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 6, 13, 22, 24-26, 33, 34, 36, 37, 54, 55, 60, 119, 121, 123, 133, 140-147 of U.S. Patent Application No. 18/696689 in view of WO2019025545 (herein Altintas) and Woroniecka KI, et al. (2020) 4-1BB Agonism Averts TIL Exhaustion and Licenses PD-1 Blockade in Glioblastoma and Other Intracranial Cancers. Clin Cancer Res. 2020 Mar 15;26(6):1349-1358 (herein Woroniecka).
Co-pending claim 1 recites a method for reducing progression of a tumor or treating cancer in a subject, comprising administration of a binding agent prior to, simultaneously with, or after the administration of an anti-PD-1 antibody or fragment thereof. With the binding agent being defined as comprising a first region binding to CD137 and a second region that binds to PD-L1, wherein the first binding region of the binding agent comprises a heavy chain variable region (VH) comprising the CDRs comprising amino acid sequence set forth in SEQ ID NO: 2-4 and a light chain variable region (VL) region comprising CDRs set forth in SEQ ID NO: 6, 8, and GAS; and b) the second binding region of the binding agent comprises a heavy chain variable region (VH) comprising CDRs set forth in SEQ ID NO: 12-14 and a light chain variable region (VL) region comprising CDRs set forth in SEQ ID NO: 16 and 18, and DDN.
Co-pending SEQ ID NO: 2-4 discloses the anti-CD137 CDRs of present SEQ ID NOs: 2-4; co-pending SEQ ID NO: 6, 8 discloses the anti-CD137 CDRs of present 6, 7, and the sequence GAS; co-pending SEQ ID NO: 12-14 discloses the anti-PD-L1 CDRs of present SEQ ID NOs: 9-11; and co-pending SEQ ID NO: 16 and 18 discloses the anti-PD-L1 CDRs of present SEQ ID NOs: 13, 14, and the sequence DDN of the present claims.
The referenced claims describe a method for treating cancer, comprising the administration of multi-specific antibody, identical to the binding agent of the current application, as well as an anti-PD-1 antibody or fragment thereof. The main difference between the present claims and the co-pending claims is that the present claims are silent regarding the additional administration of an anti-PD-1 antibody or fragment thereof. However, the claims of the referenced co-pending application encompass the limitations established in the current application.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claims allowed.
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/MATTHEW CURRAN METCALF/Examiner, Art Unit 1647 /JOANNE HAMA/Supervisory Patent Examiner, Art Unit 1647
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