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
The preliminary amendment filed 08/13/2024 is acknowledged. Claims 3-7, 14-17, 19-21, 24, 29, 31, 32, 36-41, 43, 44, and 46-48 are amended. claims 1-49 are pending and under review.
Claim Objections
Claims 21-23, 27, 28, 30, and 42 are objected to because of the following informalities: The claims recite the acronyms “PS 20” and “PS-20” without having made clear the full meaning of the terms in their first use. To advance compact prosecution, the examiner has interpreted these to mean “polysorbate 20.” Appropriate correction is required.
Applicant is advised that should claim 32 be found allowable, claim 48 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claim 48 is rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The claim does not fall within at least one of the four categories of patent eligible subject matter because it recites “use of the aqueous pharmaceutical composition of claim 1 for treating cancer,” which is not one of the four categories of subject matter that Congress deemed to be appropriate subject matter for a patent: processes, machines, manufactures, and compositions of matter (Step 1 of Subject Eligibility Analysis: NO)(see MPEP 2106.03 (I) and (II). If a claim covers material not found in any of the four statutory categories, that claim falls outside the plainly expressed scope of § 101 even if the subject matter is otherwise new and useful.” In re Nuijten, 500 F.3d 1346, 1354, 84 USPQ2d 1495, 1500 (Fed. Cir. 2007).
Therefore, claim 48 is rejected under 35 U.S.C. 101 as non-statutory subject matter.
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.
Claims 1-44 and 46-49 are rejected under 35 U.S.C. 103 as being unpatentable over the American Medical Association (AMA) in view of Gokarn et al. and Strickley et al.
Claims 1-31, 46, and 47 are drawn to an aqueous pharmaceutical composition, claims 32, 33, 48, and 49 are drawn to a method of treating cancer, claims 34-42 are drawn to a method of preparing an aqueous pharmaceutical composition, and claim 43 is drawn to a kit comprising the pharmaceutical composition.
American Medical Association (AMA) discloses a bispecific GPRC5D/CD3 antibody comprising the recited variable heavy and light chains, as well as the CDRs contained in those chains [see alignment below] (instant claims 1-6, 34-39). AMA discloses that the claimed antibody is Talquetamab [see p. 1, line 2] (instant claims 7 and 40). AMA discloses that the antibody is useful for the treatment of multiple myeloma, which is a type of cancer [see p. 1, “Therapeutic Claim”] (instant claim 32, 46, 47, 48).
Heavy and Light chain SEQ ID NOs: 9, 10, 19, and 20 aligned to Talquetamab (see AMA):
QVQLVQSGAEVKKPGASVKVSCKASGYSFTGYTMNWVRQAPGQGLEWMGLINPYNSDTNY||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||QVQLVQSGAEVKKPGASVKVSCKASGYSFTGYTMNWVRQAPGQGLEWMGLINPYNSDTNYAQKLQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARVALRVALDYWGQGTLVTVSSAS||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||AQKLQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARVALRVALDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGL||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||TKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEAAGGPSVFL||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||YSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRV||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||FPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||VSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNV||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKDIQMTQSPSSLSASVGDRVTITCKASQNVATHVGW||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||FSCSVMHEALHNHYTQKSLSLSLGKDIQMTQSPSSLSASVGDRVTITCKASQNVATHVGWYQQKPGKAPKRLIYSASYRYSGVPSRFSGSGSGTEFTLTISNLQPEDFATYYCQQYNRYP||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||YQQKPGKAPKRLIYSASYRYSGVPSRFSGSGSGTEFTLTISNLQPEDFATYYCQQYNRYPYTFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||YTFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECE||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECEVQLVESGGGLVQPGGSLRLSCAASGFTFNTYAMNWVRQAPGKGLEWVARIRSKYNNYATY||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||VQLVESGGGLVQPGGSLRLSCAASGFTFNTYAMNWVRQAPGKGLEWVARIRSKYNNYATYYAASVKGRFTISRDDSKNSLYLQMNSLKTEDTAVYYCARHGNFGNSYVSWFAYWGQGTLV||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||YAASVKGRFTISRDDSKNSLYLQMNSLKTEDTAVYYCARHGNFGNSYVSWFAYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAV||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||TVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEAAG||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||LQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQF||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||GPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQE||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFLLYSKLTVDKSR||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFLLYSKLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKQTVVTQEPSLTVSPGGTVTLTCRSSTGAV||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||WQEGNVFSCSVMHEALHNHYTQKSLSLSLGKQTVVTQEPSLTVSPGGTVTLTCRSSTGAVTTSNYANWVQQKPGQAPRGLIGGTNKRAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYY||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||TTSNYANWVQQKPGQAPRGLIGGTNKRAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNLWVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTV||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||CALWYSNLWVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTV||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||AWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS||||||APTECS
AMA does not teach or suggest an aqueous pharmaceutical composition, the claimed antibody concentrations, administration methods, or a kit comprising the antibody.
Gokarn et al. teaches a conventional stable [see p. 3051, col. 2, line 7] (instant claims 29, 34, 35, and 41) aqueous liquid formulation for monoclonal antibodies comprises 10mM acetate (instant claims 1, 2, 14), 0.01% polysorbate 20 (instant claims 1, 2, and 21), has a pH of 5.2 [see abstract] (instant claims 1, 2, 24-28, 34, and 35) (see abstract, lines 18-20), and 5% w/v sorbitol or 9% w/v sucrose [see p. 3052, col. 2, par. 3, line 6] (instant claims 1, 2, 17, 18, 27, 28, 34, 35). Gokarn et al. further teaches that such formulations are suitable for antibodies formulated 50-70 mg/mL (instant claims 2, 11, and 12).
Gokarn et al. does not teach or suggest the inclusion of EDTA, embodiments comprising a low antibody concentration, or methods of administration.
Strickley et al. reviews 126 commercially available antibodies and their corresponding antibody formulations. Strickley et al. teaches that common antibody formulations include 2.5-10% w/v sucrose [see p. 2598, table 2] (instant claims 1, 2, 17, 18, 27, 28, 34, 35), 20-25mM acetate [see p. 2602, col. 2, par. 4] (instant claims 1, 2, 14), 0.008-0.04 polysorbate 20 [see p. 2603, table 5] (instant claims 1, 2, 21-23, 27, 28, 34, and 35), the second most common pH range being 5.0-5.9 [see p. 2601, col. 1, par. 5] (instant claims 1, 2, 24-28, 34, and 35) and 20-140 ug/mL EDTA [see p. 2605, col. 1, par. 3] with most of the EDTA concentrations of the reviewed compositions being between 10-50 ug/ml [see appendix 1] (instant claims 1, 2, 19, 20, 27, 28, 34, and 35). Strickley et al. notes that intravenously administered antibody concentrations are typically 10-50 mg/mL after reconstitution (instant claims 2, 11-13, 28, 35), but teaches that antibody concentration is a recognized formulation variable, with some antibodies being as low as 0.012 mg/ml (instant claims 1, 8, 9, 10, and 34), and that concentration selection depends on factors including route of administration, desired dosage form, and dosing schedule [see p. 2598, col. 2, par. 1, lines 16 and 17]. Strickley et al. teaches that subcutaneous injection offers the advantage of self-administration [see p. 2592, col. 1, par. 3, lines 1-2] (instant claims 33 and 49). Strickley et al. teaches that most antibodies are packaged in single dose units that comprise a vial, autoinjector, or prefilled syringe [see abstract, lines 9 and 10] (instant claims 43 and 44).
It would have been obvious to formulate the known Talquetamab antibody using the conventional aqueous formulation taught Gokarn et al. and incorporate EDTA as taught by Strickley et al. because Gokarn teaches that the disclosed formulation is conventionally used to prepare stable liquid antibody formulations, and Strickley et al. teaches that EDTA is a known chelator that is conventionally used to reduce oxidation damage (instant claims 1, 2, 34, 35). It is prima facie obvious to combine two compositions, each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose. The idea of combining them flows logically from their having been individually taught in the prior art [see In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). Also see MPEP § 2144.06(I)]. Furthermore, based on the prior art, a person having ordinary skill in the art would have recognized antibody concentration and the amounts of solution specific components are formulation variables that are routinely adjusted to achieve desired stability and administration characteristics. Accordingly, selecting antibody excipient concentrations within the disclosed ranges would have constituted routine optimization of known result-effective variables, with a reasonable expectation of success because each component was known in the art to contribute to antibody stability. For example, the claimed acetate ranges of about 14-16 mM and 15mM (instant claims 15, 16, 27, 28, 34, and 35) represent intermediary values within the range of acetate concentrations conventionally used in antibody formulations as discussed above. Combining said components to generate an aqueous pharmaceutical solution is the conventional way antibody formulations are prepared, and it would have been obvious to do so after determining the appropriate amounts of each component (instant claims 34 and 35). Furthermore, given that the solution comprises the same components, it would have been expected that they would have had the same characteristics, including the claimed stability (instant claim 31).
It would have been obvious to administer the disclosed antibody formulation subcutaneously (instant claim 33) to treat cancer (instant claims 32, 46, and 48) because AMA teaches that Talquetamab is therapeutically effective for treating multiple myeloma, Strickley et al. teaches that subcutaneous administration is a conventional method to administer antibodies, and the combination of all three references collectively teaches the claimed aqueous solution. Additionally, formulating a known therapeutic antibody using conventional components would have predictably yielded a pharmaceutical composition suitable for administration.
It would have been obvious to store the pharmaceutical composition in a vial (instant claim 44) and package it together with instructions for its intended use (instant claim 43) because Talquetamab was a known therapeutic and Strickley et al. teaches that antibody therapeutic products are routinely stored in vials, packaged in kits, and distributed with prescribing information and instructions for use.
Regarding claim 30, in view of the prior art discussing the role of each component in antibody stability and the conventional parameters claimed, a person having ordinary skill in the art would have recognized that defining the stability of the formulation based on these conventional parameters would have been obvious (instant claims 30 and 42).
Instant claims 46 and 47 are rejected as they only recite intended use without conferring a structural, material, or manipulative difference on the scope of the claim.
Therefore, claims 1-44 and 46-49 are rejected under 35 U.S.C. 103.
Claims 1, 44, and 45 are rejected under 35 U.S.C. 103 as being unpatentable over the American Medical Association (AMA) in view of Gokarn et al. and Strickley et al., and in further view of Mecmesin et al.
Claim 1 is drawn to an aqueous pharmaceutical composition, and claims 44 and 45 are drawn to a container for holding the composition.
The disclosure of AMA, Gokarn et al., and Strickley et al. are discussed above.
The combination of these references does not teach or suggest that the composition be contained in a container that is a vial with a stopper that is pierceable by a syringe.
Mecmesin teaches that the majority of parenteral drug products are manufactured in glass vials and sealed with an elastomeric rubber stopper (instant claim 44). Mecmesin teaches that the vials are tested to ensure that a syringe needle is able to pass through with less than 10N of force (instant claim 45).
It would have been obvious to package the composition in a vial with a stopper that is pierceable by a needle because such vials were routinely used for sterile injectable pharmaceutical compositions and would have predictably provided a suitable container for storage and administration.
Therefore, claims 1, 44, and 45 are rejected under 35 U.S.C. 103.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Tirone D Johnson whose telephone number is (571)272-1256. The examiner can normally be reached M-F, 9-5 ET.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Stucker can be reached at (571)272-0911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/TIRONE D. JOHNSON/ Examiner, Art Unit 1675
/JEFFREY STUCKER/ Supervisory Patent Examiner, Art Unit 1675
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