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 .
DETAILED ACTION
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 1/27/2026 has been entered.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Claims 1, 38, 43, 46-47, 62-68, and 72-74 have an effective filing date of 08 FEB 2018.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 10/01/2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Election/Restriction
In the response filed on 12/18/2023, Applicant elected:
Glutamic acid as the species of buffer agent
Disaccharide sucrose as the species of saccharide
Polysorbate 80 as the species of surfactant
1 mg/mL as the species of heterodimeric antibody concentration
Liquid as the species of composition
Prostate cancer as the type of cancer
Status of Claims
Claims 1, 38, 43, 46-47, 62-68, and 72-74 are currently pending and presented for examination on the merits.
Claims 1 and 43 are amended.
Claims 2-37, 39-42, 44-45, 48-61, and 69-71 are canceled.
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.
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 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, 38, 43, 46-47, 62-68, and 72-74 are rejected under 35 U.S.C. 103 as being unpatentable over Kannan et al (AU 2013347963 A1, Previous OA), Gokarn et al (US 20080003220 A1, Previous OA), Goldberg et al (US 20160355591 A1), Zou et al (CN 104474547 A, Previous OA), Ho et al (WO 2011143545 A1, Previous OA), and further in view of Moore et al (US 20140363426 A1).
In regards to claim 1 and 64, Kannan et al teaches a liquid pharmaceutical composition [0201]. Kannan et al further teaches the pharmaceutical composition with a buffer [0203]. Kannan et al further teaches the use of surfactant [0203]. Kannan et al further teaches the use of disaccharides with the pharmaceutical composition [0203]. Kannan et al further teaches the use of heterodimeric antibodies [0204]. Kannan et al further teaches the antibody comprising a Fab, Fc, and scFv [0102]. Kannan et al further teaches antibodies with two Fab [0370]. ]. Kannan et al further teaches the use of the disaccharide sucrose [0203]. Kannan et al further teaches sucrose at 9% w/v [0381]. Kannan et al further teaches the use of the surfactant polysorbate 80 [0221]. Kannan et al further teaches buffers are used to maintain the composition at physiological acceptable levels of a pH of 4.0-5.5 [0204].
Kannan et al does not specifically teach a buffer and a buffer concentration of between 10 to 50 mM. However, this deficiency is made up in the teachings of Gokarn et al.
Gokarn et al teaches a biopharmaceutical formulation comprising antibody with Fab and scFv [0014]. Gokarn et al further teaches using a buffer at a concentration of 10 mM [0032].
Kannan et al does not specifically teach glutamic acid as a buffer. However, this deficiency is made up in the teachings of Goldenberg et al.
Goldenberg et al teaches a buffer made with glutamic acid [0361]. Goldenberg et al further teaches using glutamic acid increases the maximum concentration of antibody the buffer can hold without precipitation [0361].
Kannan et al does not specifically teach concentrations of surfactant. However, this deficiency is made up in the teachings of Zou et al.
Zou et al teaches the use of surfactant with w/V of 0.1% [0007].
Kannan et al does not specifically teach the scFv binds CD3. However, this deficiency is made up in the teachings of Ho et al.
Ho et al teaches a heterodimeric antibody binding CD3, including an scFv molecule [Line 27, pg. 28; Line 9, pg. 13]. Ho et al further teaches the heterodimeric antibody is present in the pharmaceutical composition [Example 16, pg. 63].
Kannan et al does not specifically teach a heterodimeric antibody comprising three antigen binding domains. However, this deficiency is made up in the teachings of Moore et al.
Moore et al teaches heterodimeric bispecific antibody formats that enable the engagement of distinct target antigens, see [0006]. At [0007], Moore et al. teach that “[i]n one aspect, the present invention provides heterodimeric antibodies comprising a first monomer comprising a first heavy chain constant domain comprising a first variant Fc domain and a first antigen binding domain and a second monomer comprising a second heavy chain constant domain comprising a second variant Fc domain and a second antigen binding domain.” At Figure 1B, Moore et al. teach the “triple F” format, which is also known as the “bottle-opener” configuration. This figuration comprises:
i) a first monomer comprising
A) a single chain Fv domain (scFv) that binds a first antigen, wherein said scFv domain comprises:
1) a first variable heavy domain (VH1);
2) a scFv linker; and
3) a first variable light domain (VL1); and
B) a first Fc domain;
ii) a second monomer comprising a VH2-CH1-hinge-CH2-CH3 heavy chain, wherein VH2 is a second variable heavy domain and CH2-CH3 is a second Fc domain; and
iii) a light chain comprising a second variable light domain (VL2) and a constant light domain (CL), wherein said VH2 and said VL2 bind a second antigen.
One of ordinary skill, before the effective filing date would have been motivated to combine Kannan’s liquid pharmaceutical composition comprising a heterodimeric antibody with Fab, Fc, and scFv, buffer, surfactant, the disaccharide sucrose at 9% w/V, polysorbate 80, with Gokarn’s composition with a buffer at a concentration of 10 mM, with Goldberg’s method of using glutamic acid for a buffer, with Zou’s use of surfactant with w/V of 0.1% with Ho’s pharmaceutical composition comprising a heterodimeric antibody binding CD3, with Moore’s heterodimeric antibody comprising three antigen binding domains. The idea of combining them flows logically from their having been individually taught in the prior art (MPEP 2144.06). Combining prior art elements according to known methods to yield predictable results is an exemplary rationale for a prima facie case of obviousness. MPEP2143. It would have been prima facie obvious to combine Kannan, Gokarn, Goldberg, Ho, and Moore’s pharmaceutical compositions for a pharmaceutical composition comprising a) a heterodimeric antibody that binds CD3, b) glutamate in an amount of 10 mM, c) a surfactant polysorbate 80 in an amount of 0.1% w/V, and d) sucrose at 9% w/V, wherein the heterodimeric antibody comprises three antigen binding domains and an Fc, wherein the binding domains are two Fabs and a scFv, because the pharmaceutical compositions could be used for treating diseases. Furthermore, Goldberg teaches glutamic acid increases the concentration of antibodies in the buffer without precipitation, and one of ordinary skill in the art would have been motivated to determine the optimal level of glutamic acid to ensure maximum solubility of a desired antibody, thus arriving at the instantly claimed invention.
In regards to claim 38, Kannan et al teaches sucrose at 9% w/v [0381].
In regards to claim 43, Zou et al teaches the use of surfactant with w/V of 0.01% [0007].
In regards to claim 46, Kannan et al teaches buffers are used to maintain the composition at physiological acceptable levels of a pH of 4.0-5.5 [0204].
In regards to claim 47, Gokarn et al teaches a pharmaceutical composition with osmolarity of 300 mOsm/kg [0057].
In regards to claims 62 and 63, Gokarn et al teaches the polyol excipient sorbitol at 5% w/V [0032].
In regards to claims 65-68, Ho et al teaches the heterodimeric antibody is present in the pharmaceutical composition from about 1-200 mg/mL [Line 3, pg. 43].
In regards to claim 72, Kannan et al teaches heterodimeric antibodies treating cancer [Example 10, 0369].
In regards to claim 73, Kannan et al teaches treating multiple myeloma with heterodimeric antibodies [0176].
In regards to claim 74, Ho et al teaches the antibodies used to treat prostate cancer [Example 16, pg. 63].
Applicant’s Arguments:
the Office has not established that the cited art (when taken alone or in combination) discloses an antibody formulation comprising a glutamate buffer as recited in the pending claims.
Kannan provides no guidance regarding which of these components in particular when combined would be suitable for a stable formulation for a heterodimeric antibody having the format recited in the claims.
Kannan "does not specifically teach glutamic acid as a buffer and a buffer concentration of between 10 to 50 mM."
There is nothing in Gokarn that would have motivated the skilled person to abandon the preferred propionate buffer and replace it with a component that is provided as an example of a potential "excipient" within a laundry list of other potential excipient options.
There is nothing in Zou that suggests that formulation components (and amounts of such components) that are suitable for an IgY formulations would also be suitable for the heterodimeric antibody recited in the claims. Accordingly, a person of ordinary skill in the art would have had no reason or motivation to look to Zou for guidance on the amount of surfactant to include in a heterodimeric antibody formulation comprising three antigen binding domains.
Ho provides generic disclosure of various components for a heterodimeric antibody formulation, but not the particular combination of components in the particular amounts required by the instant claims.
The disclosures of Kannan, Gokarn, Zou, Ho, and Moore (taken alone or in combination) do not disclose a formulation comprising, inter alia, a glutamate buffer.
Examiner’s Response:
Applicant states, “The disclosures of Kannan, Gokarn, Zou, Ho, and Moore (taken alone or in combination) do not disclose a formulation comprising, inter alia, a glutamate buffer.”
Goldenberg et al teaches a buffer made with glutamic acid [0361]. Goldenberg et al further teaches using glutamic acid to increases the maximum concentration of antibody the buffer can hold without precipitation [0361].
One of ordinary skill in the art would recognize that glutamic acid was a known additive to buffers, that allows for increase concentration of antibodies in solution, without precipitating out of solution. Furthermore, one of ordinary skill would be motivated to use glutamic acid due to this beneficial property.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DENNIS JOHN SULLIVAN whose telephone number is (571)272-0509. The examiner can normally be reached Mon - Fri: 7:30AM - 4:30PM.
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/DENNIS J SULLIVAN/Examiner, Art Unit 1642
/NELSON B MOSELEY II/Primary Examiner, Art Unit 1642