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
Claims 1-3, 11-14, 17, 18, and 28-43 are pending.
Claims 1-3, 11-14, 17, 18, and 28-43 are under examination on the merits.
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 1-3, 11-14, 17, 18, and 28-43 have an effective filing date of 12/15/2018, corresponding to PRO 62/631,043.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 09/14/2023, 12/27/2023, and 10/02/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Notes on the Prior Art
At the effective filing date of the invention, bispecific antibodies that bind to CD3 and a disease antigen (DA, such as CD19) were known in the art. For example Johnson et al. (US PG PUB 20170247452, publication date: 08/31/2017) teach a CD19 x CD3 bispecific antibody that comprises 1) a heavy chain variable region (VH) and a light chain variable region (VL) that form a CD19-binding moiety, a 2) a VH and a VL that form a CD3-binding moiety, and 3) an Fc region, see claim 1. The prior art does not teach a DA x CD3 bispecific antibody that comprises the anti-CD3 heavy chain CDRs 1-3 of SEQ ID NO(s): 99, 58, and 59, respectively, and the light chain CDRs 1-3 of SEQ ID NO(s): 60-62, respectively. The instantly claimed DA x CD3 bispecific antibody is also not an obvious variant of any art-known DA x CD3 bispecific antibody, and as such the instantly claimed DA x CD3 bispecific antibody is free of the prior art.
Claim Rejections
Nonstatutory 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.
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Claims 1-3, 11-14, 17, and 28-34 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 and 17 of U.S. Patent No. 11,685,781 in view of Johnson et al. (US PG PUB 2017/0198045, publication date: 07/13/2017).
Both sets of claims recite a disease antigen (DA) epitope x CD3 epitope bispecific antibody that comprises the anti-CD3 heavy chain CDRs 1-3 of SEQ ID NO(s): 99, 58, and 59, respectively, which are comprised within the VH of SEQ ID NO: 98, and the light chain CDRs 1-3 of SEQ ID NO(s): 60-62, respectively, which are comprised within the VH of SEQ ID NO: 56, wherein said DA×CD3 Binding Molecule comprises: a first polypeptide chain and a second polypeptide chain, covalently bonded to one another, wherein: (A) the first polypeptide chain comprises, in the N-terminal to C-terminal direction: (i) a Domain 1, comprising: (1) a sub-Domain (1A), which comprises a VL Domain of a monoclonal antibody capable of binding to said epitope of the DA (VL.sub.DA); and (2) a sub-Domain (1B), which comprises a VH Domain of a monoclonal antibody capable of binding to said epitope of CD3 (VH.sub.CD3); wherein said sub-Domains 1A and 1B are separated from one another by a peptide Linker; and (ii) a Domain 2, wherein said Domain 2 is a Heterodimer-Promoting Domain; (B) the second polypeptide chain comprises, in the N-terminal to C-terminal direction: (i) a Domain 1, comprising: (1) a sub-Domain (1A), which comprises a VL Domain of said monoclonal antibody capable of binding to said epitope of CD3 (VL.sub.CD3); and (2) a sub-Domain (1B), which comprises a VH Domain of said monoclonal antibody capable of binding to said epitope of the DA (VH.sub.DA); wherein said sub-Domains 1A and 1B are separated from one another by a peptide Linker; (ii) a Domain 2, wherein said Domain 2 is a Heterodimer-Promoting Domain, wherein said Heterodimer-Promoting Domain of said first and said second polypeptide chains are different; and wherein: the VL Domain of the first polypeptide chain and the VH Domain of the second polypeptide chain associate to form the DA-Binding Domain, and the VH Domain of the first polypeptide chain and the VL Domain of the second polypeptide chain associate to form the CD3-Binding Domain, wherein: (a) said Heterodimer-Promoting Domain of said first polypeptide chain is an E-coil Domain, and said Heterodimer-Promoting Domain of said second polypeptide chain is a K-coil Domain; or (b) said Heterodimer-Promoting Domain of said first polypeptide chain is a K-coil Domain, and said Heterodimer-Promoting Domain of said second polypeptide chain is an E-coil Domain, and wherein the first or second polypeptide chain additionally comprises a Domain 3 comprising a CH2 and CH3 Domain of an immunoglobulin Fc Domain.
The conflicting claims do not recite a DA epitope x CD3 epitope bispecific antibody that comprises a DA-binding moiety, wherein said DA-binding moiety is 5T4-binding moiety that comprises the VH of SEQ ID NO: 156 and the VL of SEQ ID NO: 157; however Johnson et al. teach the 5T4 tumor antigen, as well as a 5T4-binding moiety that comprises the VH of SEQ ID NO: 48, which shares 100% homology with the instant SEQ ID NO: 156, and the VL of SEQ ID NO: 47 , which shares 100% homology with the instant SEQ ID NO: 157. See [0280] - [0283]. At [0012], Johnson et al. teach “a method of treating cancer which comprises administering an effective amount of the above-described pharmaceutical composition to an individual in need thereof, wherein the Disease-Associated Antigen is the cancer antigen.”
In view of these teachings, one of ordinary skill in the art would have been motivated to substitute the CD123-binding moiety of the conflicting claims to recite the 5T4-binding moiety of Johnson et al., because there would have been a reasonable expectation that the resultant bispecific antibody is effective in treating 5T4-expressing cancers. The method of the conflicting claims and Johnson et al. meets the limitations of claims 1-3, 11-14, and 28-34.
With respect to the instant claim 17, conflicting claim 18 recites a pharmaceutical composition that comprises a DA epitope x CD3 epitope bispecific antibody and a pharmaceutically acceptable carrier.
Therefore the instant claims are prima facie obvious over the conflicting claims in view of Johnson et al.
Claims 18 and 35-43 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8, 17, and 33 of U.S. Patent No. 11,685,781 in view of Johnson et al. (US PG PUB 2017/0198045, publication date: 07/13/2017), as applied to claims 1-3, 11-14, 17, and 28-34, and Castro et al. (Leukemia, 26: 1487-1498, 2012).
As indicated above one of ordinary skill in the art would have been motivated to substitute the CD123-binding moiety of the conflicting claims to recite the 5T4-binding moiety of Johnson et al., because there would have been a reasonable expectation that the resultant bispecific antibody is effective in treating 5T4-expressing cancers.
Castro et al. teach that anti-5T4 antibodies may be used for the targeted immunotherapy of high risk pre-B-ALL (acute lymphoblastic leukemia), see Abstract. At p. 2, Castro et al. teach that “[t]he expression of 5T4 on normal tissue is restricted, but it is upregulated in many carcinomas and overexpression in tumours has been associated with a poorer clinical outcome (11). Recently, it has been shown that 5T4 is expressed on tumour initiating cells and is associated with the worse clinical outcome in non-small cell lung cancer. While mature hematopoietic cells lack the expression of 5T4, open access microarray data suggest that 5T4 is present during the early stages of normal B cell development in particular at the pro- and pre-B cell phase (Supplementary Fig. S1). Here we have investigated 5T4 expression in pre-B-ALL disease and shown an association with high risk of relapse which is correlated to invasive and chemotactic behaviour.”
In view of these teachings, one of ordinary skill in the art would have been motivated to administer the 5T4 epitope x CD3 epitope bispecific antibody of the conflicting claims and Johnson et al. to pre-B-ALL disease patients, because there would have been a reasonable expectation that such a method would provide a therapeutic benefit to pre-B-ALL disease patients by bringing cytotoxic T cells into close proximity with 5T4-expressing pre-B-ALL cells, which could lead to the destruction of said 5T4-expressing pre-B-ALL cells. The method of the conflicting claims, Johnson et al., and Castro et al. meets the limitations of claims 18, 37, and 38.
With respect to claims 39-42, the conflicting claims also recite the administration of a DA epitope x CD3 epitope bispecific antibody via intravenous administration or infusion at a dosage of about 0.01 μg/kg to about 30 mg/kg of said subject's body weight, wherein the pharmaceutical composition is administered once a week, once every two weeks, or once a month.
With respect to claims 35 and 36, absent evidence to the contrary, it appears that substituting the CD123-binding domains of the first polypeptide of SEQ ID NO: 179 and the second polypeptide of SEQ ID NO: 175 with the anti-5T4 variable regions of Johnson et al. would yield a first polypeptide of SEQ ID NO: 184 and a second polypeptide of SEQ ID NO: 181.
With respect to claim 43, conflicting claim 33 recites host cells that comprises polynucleotides that encode antibodies of the invention.
Therefore the instant claims are prima facie obvious over the conflicting claims in view of Johnson et al. and Castro et al.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NELSON B MOSELEY II whose telephone number is (571)272-6221. The examiner can normally be reached on M-F, 9:00-6:00 EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Samira Jean-Louis, can be reached at 571-270-3503. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/NELSON B MOSELEY II/Primary Examiner, Art Unit 1642
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