DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant's amendment and remarks, filed 2/10/26, are acknowledged.
Claims 1, 4, 6, 8, 10, 12, 14, 27, 39, 46 have been amended.
Claims 1, 4, 6, 8, 10, 12, 14, 27, 34, 39, and 46 are pending and are under examination. .
In view of Applicant’s amendments, only the following rejections remain.
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.
Claim 1, 4, 6, 8, 10, 12, 14, 27, 34, 39 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 20110293619, in view of WO2020/048525.
The ‘619 publication teaches a bispecific antibody molecule comprising a first binding domain that binds to CD3 linked to a second binding domain that binds to tumor antigen PSMA. The ‘619 publication teaches CD3 scFV with an orientation of VH-VL in SEQ ID NO: 185, that is identical to SEQ ID NO: 13 of the instant application. Said SEQ ID NO: 185 has CDRs of SEQ ID NO: 3, 2, and 5, 9, 7, and 10, and comprises a VH and VL at least 80% identical to SEQ ID NO: 11 and 12 (see paragraph 112, in particular). The ‘619 publication also teaches said CD3 scFV in the opposite orientation of VL-VH, which would result in a sequence identical to SEQ ID NO: 16 of the instant application. The ‘619 publication teaches PSMA VL of SEQ ID NO: 485, which is identical to residues 1-107 of SEQ ID NO: 30 of the instant application, and comprises CDRs of SEQ ID NO: 25, 26, and 27. The ‘619 publication teaches a PSMA VH of SEQ ID NO: 490, which comprises a VH region identical to residues 1-123 of SEQ ID NO: 31, and comprises CDRs of SEQ ID NO: 20,18, and 21 of the instant application.
The reference differs from the claimed invention in that it does not explicitly teach that the PSMA binding region is a Fab.
WO2020/048525 teaches a bispecific antibody antigen binding protein that binds to CD3 and a tumor antigen, comprising an scFV that binds to CD3 and a Fab that binds to a tumor antigen, wherein the scFV is connected to the N-terminus of the anti-tumor Fab via a linker, i.e. a polypeptide complex of the formula CD3 scFV-Linker-Tumor Fab, or A-L-B as recited in the present claims, see page 3, in particular. WO2020/048525 teaches that the C-terminus of CD3 scFV can be connected to the N-terminus of either the VH or the VL of the anti-tumor Fab (see pages 3-4 and the drawings, in particular). WO2020/048525 teaches that the bispecific format has several advantages compared to other bispecific proteins known in the art, including enhanced cytotoxic activities against cancer cells and improved safety profiles (see page 9, in particular). WO2020/048525 teaches that the CD3 scFV comprises a VH of SEQ ID NO: 15 (which comprises CDRs of SEQ ID NOS: 4, 2, and 5 of the instant application) and a VL of SEQ ID NO: 16 (which comprises CDRs of SEQ ID NO: 9, 7, and 10 of the instant application, see page 62, in particular). WO2020/048525 teaches that the CD3 scFV can be in the orientation N’-VH-VL-C’ or N’-VL-VH-C’, with a linker connecting the VH and VL (see pages 62-63, in particular). WO2020/048525 teaches that the Fab is constructed with a VH-CH1 and a VL-CL with a CPPC sequence at the C-terminus of the CH1 and CL (See page 64, in particular). WO2020/048525 teaches CH1 of SEQ ID NO: 18 and CL of SEQ ID NO: 19 (see page 65, in particular). WO2020/048525 teaches that the linker connecting the scFV and the Fab can be GGGGS (see page 72, in particular). WO2020/048525 teaches constructing the bispecific proteins as a complex between a first and second polypeptide, wherein the construct can be assembled in a variety of configurations. For example, WO2020/048525 teaches that the first polypeptide can have a N’-anti-CD3 VL-L1anti-CD3VH-L2-anti-CD19(tumor antigen)VL-CL-C’ and the second polypeptide comprises N’anti-tumor antigen VH-CH1-C’, This would be a structure wherein the linker (L2) connects the Fab light chain polypeptide to the C-terminus of the scFV heavy chain variable domain, as recited in claim 39.
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to construct the bispecific anti-CD3 and anti-PSMA antibody of the ‘619 publication, using the bispecific antibody antigen binding protein configuration taught by WO2020/048525. The ordinary artisan at the time the invention was made would have been motivated to do so with a reasonable expectation of success, because WO2020/048525 teaches that the bispecific format has several advantages compared to other bispecific proteins known in the art, including enhanced cytotoxic activities against cancer cells and improved safety profiles.
Doing so would result in sequences within the scope of those recited in the claims of the instant application. For example, following the guidance of WO2020/048525, one could use the VH and VL of the PSMA tumor antigen antibody as the anti-tumor Fab by linking the VH and VL of SEQ ID NO: 490 and 485 of the ‘619 publication, to the CH1 and CL of SEQ ID NO: 18 and 19 of WO2020/048525. This would arrive at a sequence identical to SEQ ID NO: 28-31 of the instant application, which represent VH-CH1 or VL-CL. Regarding claim 39, as noted above, WO2020/048525 teaches a construct wherein the first polypeptide can have a structure N’-anti-CD3 VL-L1anti-CD3VH-L2-anti-CD19(tumor antigen)VL-CL-C’ and the second polypeptide comprises N’anti-tumor antigen VH-CH1-C’. To arrive at SEQ ID NO: 31 and 36 of the instant application, one would simply need to substitute the CD3scFV and anti-PSMA-VH-VL of the ‘619 publication, into the construct taught by WO2020/048525 as the CD3scFV and tumor antigen specific Fab. For example, SEQ ID NO: 36 of the instant application would be identical to a construct built using the CD3 scFV from the ‘619 publication in the orientation anti-CD3-VL-L1anti-CD3VH, GGGGS as L2, as taught in WO2020/048525, anti-PSMA-VL of SEQ ID NO: 485 from the ‘619 publication, and CL of SEQ ID NO: 19 of WO2020/048525 as anti-tumor antigen VL-CL, with CPPS added to the C-terminus, as taught by WO2020/048525. SEQ ID NO: 31 is identical to the VH of SEQ ID NO: 490 of the ‘619 publication, linked to CH1 of SEQ ID NO: 18 and CPPS of WO2020/048525.
Applicant’s argument filed 2/10/26 have been fully considered, but they are not persuasive.
Applicant argues that the specification demonstrates unexpected results for the claimed configuration wherein the C-terminus of the scFv is connected to the N-terminus of the Fab light chain. Applicant cites Example 3, which shows that connecting via the Fab light chain (Ab5) had a significantly lower IC50 than when the scFV was connected to the N-terminus of the Fab heavy chain (Ab-4).
Ab5 has a Fab heavy chain polypeptide of SEQ ID NO: 31 and second polypeptide of SEQ ID NO: 38, which represents a Fab light chain polypeptide connected to the C-terminus of the CD3 scFV, wherein the Fab light chain polypeptide is connected to the C-terminus of scFV light chain variable region (claimed in claim 46). However, these results are not commensurate in scope with the other claims. For example, claim 1 encompasses any CD3 scFV sequence, and the claims also encompass connecting the Fab light chain to the C-terminus of the scFV heavy chain variable region. For example, the specification discloses that Ab3 (which is claimed in claim 39), which has the Fab light chain connected to the C-terminus of the scFV heavy chain variable region has the highest IC50 of all the constructs tested (see Figs. 7-8). In fact, said Ab-3 has a higher IC50 than Ab-2, which is connected to the scFV via the Fab heavy chain polypeptide. In other words, the data do not demonstrate that the low IC50 occurs over the full scope of the instant claims, and do not demonstrate that it flows from connecting the scFV to the N-terminus of the Fab light chain, as argued by Applicant. Rather, the specification only demonstrates unexpectedly low IC50 for the specific construct in claim 46, and not for the other polypeptide constructs encompassed by the present claims, including for example Ab3 (claimed in claim 39). Therefore, the unexpected results are not commensurate in scope with the instant claims. The unexpected results shown in the instant specification are commensurate with dependent claim 46, and the rejection of that claim under 35 U.S.C. 103 is withdrawn.
The following are new grounds of rejection necessitated by Applicant’s claim amendments.
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.
Claims 39 and 46 are 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.
Claims 39 and 46 recites the limitation "the peptide" in lines 4-5. There is insufficient antecedent basis for this limitation in the claim.
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMY E JUEDES whose telephone number is (571)272-4471. The examiner can normally be reached on M-F from 7am to 3pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu can be reached on 571-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Amy E. Juedes
Patent Examiner
Technology Center 1600
/AMY E JUEDES/Primary Examiner, Art Unit 1644