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 .
Continued Examination Under 37 CFR 1.114
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 22May2026 has been entered.
Claims Status
The Amendment filed on 22May2026 is acknowledged in which claim(s) 1-19, 21-23, were canceled by Applicant.
Claim(s) 20 and 24-49 is/are currently pending and presented for examination on the merits.
Response to Amendment
All previous rejections and/or objections of claim(s) 3, 5-19 is/are moot in view of claim cancelation.
The rejection(s) of claim(s) 24-38, 40-49 under 35 U.S.C. § 103 have been withdrawn in view of the recent claim amendment filed on 22May2026, which added new limitations to the claims not considered in the previous rejections, and necessitated new rejections.
All other previously presented rejection(s) are maintained/maintained in modified form as necessitated by amendment. Applicant' s amendments and arguments have been thoroughly reviewed, but are not persuasive to place the claims in condition for allowance for the reasons that follow.
Rejections Maintained in Modified Form as Necessitated by Amendment
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 20, 24-32, and 35-47 is/are rejected under 35 U.S.C. 103 as being obvious US 2022/0185885 A1 (hereinafter “US885”), in view of Stamova et al. (Antibodies 2012, 1, 172-198; hereinafter “Stamova”) as evidenced by Gravelle et al. (Oncotarget, 2017, vol. 8, No. 27, pp: 44960-44975; hereinafter “Gravelle”) and Krishnan et al. (Am J Surg Pathol 2010;34:178–189; hereinafter “Krishnan”), and US 10,266,593 B2 (hereinafter “US593”).
The applied reference has a common Assignee and Inventors with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2). Specifically, the instant application includes a joint inventor (SHIMBO, Takuya) that is not listed as a joint inventor of the earlier filed US885 patent application.
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
Regarding instant claims 20, 40-47, US885 teaches methods for preventing, suppressing the progression of symptoms of, suppressing the recurrence of, and/or treating autoimmune diseases, comprising administering to a patient an effective amount of the PD1/CD19 bispecific antibody (bsAb) [e.g., pg. 34, “[7-1]”], and further that the first arm of the bsAb binds PD1 and the second arm binds to CD19 [e.g., ¶ 0485-0486], and that anti-PD1/anti-CD19 bsAbs have been previously known to treat tumors [e.g., ¶ 0005]. US885 further teaches an anti-PD1 first arm comprising: a VH comprising any one of SEQ ID Nos: 1-5; and a VL comprising the amino acid of SEQ ID No. 25, which are the same as instant claimed VH (SEQ ID NOs: 1-5) and VL (SEQ ID NO: 25) sequences (see alignments below) [e.g., ¶ 0388, “[83]”; fig. 6]. US885 also teaches “There are several reports regarding PD1 bispecific antibodies to treat autoimmune diseases so far…one target of which is CD3 that is a member of T cell receptor complex.” [e.g., ¶ 0004].
Alignment of PD1 arm VH domain instant SEQ ID NO: 1 (with HCDR SEQ ID Nos 6-8) and US885 SEQ ID 1:
PNG
media_image1.png
320
653
media_image1.png
Greyscale
Alignment of PD1 arm VH domain instant SEQ ID NO: 2 (with HCDR SEQ ID Nos 9-11) and US885 SEQ ID 2:
PNG
media_image2.png
312
646
media_image2.png
Greyscale
Alignment of PD1 arm VH domain instant SEQ ID NO: 3 (with HCDR SEQ ID Nos 12-14) and US885 SEQ ID 3:
PNG
media_image3.png
314
648
media_image3.png
Greyscale
Alignment of PD1 arm VH domain instant SEQ ID NOs: 4-5 (with HCDR SEQ ID Nos 15-17 or 18-20, which are identical) and US885 SEQ IDs 4-5:
PNG
media_image4.png
447
647
media_image4.png
Greyscale
Alignment of common PD1 arm VL instant SEQ ID NO: 25 (with LCDR SEQ ID NOs: 26-28) and US885 SEQ ID NO: 25:
PNG
media_image5.png
223
708
media_image5.png
Greyscale
Regarding instant claims 24-25, US885 further teaches the bispecific antibody is an IgG that is an IgG1 or IgG4 antibody[e.g., ¶ 0411].
Regarding instant claims 26-32, 35, US885 further teaches the Fc receptor of the IgG1 antibody is eliminated or decreased (attenuated) [e.g., ¶ 0506]. US885 teaches substitution(s)/deletion(s) according to the EU numbering system, including but not limited to: (I) two heavy IgG1 heavy chain constant regions, wherein each heavy chain comprises L235G and/or G236R substitution(s) [e.g., ¶ 0506]; (II) the anti-PD1 (e.g., first arm) VH domain comprises L351K/D, T366K/E substitution(s) and the second arm VH domain L351D/K, L368E/K substitution(s) [e.g., ¶ 0507]; and that the two CH regions of IgG1 each comprise K447 deletions [e.g., ¶ 0566]. US885 further teaches an IgG4 antibody comprising two CH regions comprising S228P substitution(s), according to the EU numbering system [e.g., ¶ 0411, “[97]”].
Regarding instant claims 36-39, US885 further teaches the bsAb first (anti-PD1) arm comprises a CH region of SEQ ID NO: 23, which is the same as instant claimed PD1 (first) arm CH domain of SEQ ID NO: 23 [e.g., claim 36(A)]; the second arm comprises a CH region of SEQ ID NO: 24, which is the same as instant claimed CD3 (second) arm CH domain of SEQ ID NO: 24 [e.g., claim 36(c)]; and the first and second arms comprise a CL of SEQ ID NO: 29, which is the same as instant claimed first (PD1) and second (CD3) arm CL of SEQ ID NO: 29 (see alignments below).
Alignment of instant claimed PD1 CH domain (SEQ ID NO: 23) with US885 SEQ ID 23:
PNG
media_image6.png
577
719
media_image6.png
Greyscale
Alignment of instant claimed CD3 CH domain (SEQ ID NO: 24) with US885 SEQ ID 24:
PNG
media_image7.png
570
709
media_image7.png
Greyscale
Alignment of instant claimed CL region (SEQ ID NO: 29) with US885 SEQ ID 29:
PNG
media_image8.png
232
704
media_image8.png
Greyscale
US885 does not expressly teach an anti-PD1/anti-CD3 bsAb is administered to treat hematological cancer, or that the hematological cancers treated include peripheral T cell lymphoma, DLBCL, CLL, and HL.
Stamova teaches cancer immunotherapy by retargeting of immune effector cells via recombinant bispecific antibody (bsAb) constructs [e.g., title, abstract]. Stamova further teaches bsAbs can bind simultaneously to a tumor antigen and an activating receptor on the effector cell, triggering efficient effector activation and resulting in the eradication of the malignant cell, and further that the activating receptor of choice on T cells is the CD3 complex due to its expression on all T cells and strong activation response [e.g., pg. 175, ¶ 3; fig. 3]. Stamova teaches tandem scFvs comprising an anti-CD3 and an anti-TAA domain are termed bispecific T cell engagers (BiTEs) [e.g., pg. 178, ¶ 3]. Stamova further teaches BiTEs can activate T cells without the need of a costimulatory signal. Stamova teaches that activated TAA-specific T cells play a major role in the control of tumor growth and killing [e.g., pg. 173, ¶ 6]. Stamova further teaches the aberrant (e.g., cancer) cell targets are “generally selected among TAAs of hematological malignancies” [e.g., pg. 175, ¶ 4]. PD1 is a known to be expressed on (e.g., a TAA) hematological cancers including peripheral T cell lymphoma, DLBCL, CLL, and HL, as evidenced by Gravelle [e.g., pgs. 44961-44962, “The Biology…”; tbl. 1; pg. 44969, “Clinical significance…”] and Krishnan [e.g., title, abstract; tbl. 1].
US593 teaches human CD3 binding antibodies, CD3 antigen binding domain sequences, bispecific antibodies comprising an anti-CD3 arm, and the use of anti-CD3/TAA antibodies to treat a tumor [e.g., pg. 1, title, abstract; col 1, lines 16-39]. US593 teaches a CD3 binding domain, which are the same as the instant claimed SEQ ID NOs: 36 and 25 [e.g., figs 23B, 25].
Alignment of CD3 arm instant claimed VH (SEQ ID NO: 36, HDCRs 37-39) and VL (SEQ ID NO: 25, LCDRs 26-28)with US593 SEQ ID NO: 54 and 45 (VH and VL separated by “xxx” for ease of review):
PNG
media_image9.png
410
736
media_image9.png
Greyscale
It would have been prima facie obvious to a person having ordinary skill in the art (PHOSITA) before the effective filing date of the claimed invention to substitute the (1) disease indication(s) as well as the (2) CD19 binding domain in the method of treating autoimmune disease comprising administering an anti-PD1 /anti-CD19 bispecific antibody (bsAb) as taught by US885, with the (1) anti-PD1/anti-CD19 bsAb treating cancer as taught by US885, and (2) the CD3 arm of a bsAb to treat hematological malignancies as taught by Stramova and US593, to arrive at the instant method of treating hematological cancer comprising administration of the instant claimed anti-PD1/anti-CD3 bsAb. A PHOSITA would have been motivated to substitute the (1) treatment of cancer(s) as taught by US885 in place of the treatment of autoimmune disease as taught by US885, because US885 teaches that anti-PD1/anti-CD19 bsAbs were previously reported to treat cancer; and (2) the anti-CD3 arm as taught by US593 and Stamova in place of the anti-CD19 arm as taught by US885, because US885 teaches that anti-PD1/anti-CD19 bsAbs were previously reported to treat cancer, Stamova and US593 teach anti-TAA/CD3 bsAbs to treat cancer, US593 teaches the anti-CD3 arm sequence, and Stamova teaches that anti-TAA (e.g., anti-PD1 in T cell lymphomas) and anti-CD3 bispecific T cell engagers are effective anti-cancer therapeutics because the CD3 arm activates T cells to kill the cell that is bound by the TAA binding arm (e.g., a cancer cell), and the cancer-cell targeting arm antigen is generally selected among TAAs of hematological malignancies (see rejection above for details). There would have been a reasonable expectation of success for a PHOSITA to substitute (1) the treatment of cancer in place of the treatment of autoimmune disease as taught by US885 because US885 teaches that anti-PD1/anti-CD19 bsAbs were previously reported to treat cancer, and (2) the anti-CD3 arm as taught by US593 and Stamova in place of the anti-CD19 arm as taught by US885, because US885, Stamova, and US593 all teach bsAbs for treating cancer, Stamova and US593 teach the well-known in the art bispecific T cell engager approach to activate T cells and direct killing to the cell bound by the anti-TAA arm of the bsAb, and US593 further teaches the sequences required to construct an anti-CD3 binding domain (e.g., a CD3 arm). Additionally, the bispecific T cell engager approach is unique in that it relies on activating T cells and simultaneously binding (bringing into proximity for killing) cells that express the TAA that the anti-TAA arm binds, which works with both agonist and antagonist anti-TAA binding arms because the mechanism relies on the co-localization of tumor cell target via TAA binding and T cell (e.g., by the CD3 binding arm) while simultaneously activating T cells (e.g., via CD3 binding). However, a PHOSITA would recognize that while the bispecific T cell engager (e.g., a bsAb) platform would work with either an agonist or antagonist anti-PD1 arm, that there may be additional benefit of an anti-PD1 agonist arm because activation (agonism) of the PD1 receptor suppresses growth, which in the case of a PD1 TAA would necessarily be expected to suppress tumor growth. . This rationale aligns with the principle of simple substitution of one known element for another to obtain predictable results, supporting a conclusion of obviousness (see MPEP § 2141).
Further, it would have been obvious to a PHOSITA to modify the modified method administering an anti-PD1/anti-CD3 bsAb to treat hematological cancer of US885, Stamova, and US593 (see above) to include an anti-PD1/anti-CD3 bsAb for treating hematological cancer wherein the hematological cancer is (1) peripheral T cell lymphoma, (2) diffuse large B cell lymphoma (DLBCL), (c) classical Hodgkin lymphoma (HL), or (4) chronic lymphocytic leukemia (CLL), because the anti-PD1 TAA is expressed in peripheral T cell lymphoma, DLBCL, HL, and CLL, as evidenced by Gravelle and Krishnan (see above). Additionally, US885 and Stamova teach bsAbs are used in cancer therapy, and Stamova further teaches that the anti-TAA (e.g., PD1) and anti-CD3 is a bispecific T cell engager which is well known in the art approach to target tumor cells for killing by T cells. There is an expectation of success for a PHOPSITA to substitute the specific hematological cancer indication(s) (e.g., peripheral T cell lymphoma, DLBCL, HL, or CLL) in place of the broad hematological cancer indication treated by an anti-PD1/anti-CD3 bsAb administration as collectively taught by US885, Stamova, and US593, because Stamova teaches bispecific T cell engagers are effective anti-hematological cancer therapies when the bispecific comprises a CD3 arm to activate T cells and an anti-TAA (e.g., PD1) arm, and PD1 is a TAA known in the art to be expressed on peripheral T cell lymphoma, DLBCL, HL and CLL, as evidenced by Gravelle and Krishnan (see rejection above for details). This rationale aligns with the principle of simple substitution of one known element for another to obtain predictable results, supporting a conclusion of obviousness (see MPEP § 2141).
Thus, the invention as a whole is prima facie obvious over the references, especially in the absence of evidence to the contrary.
Claim(s) 33 -34 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 2022/0185885 A1 (hereinafter “US885”), in view of Stamova et al. (Antibodies 2012, 1, 172-198; hereinafter “Stamova”) as evidenced by Gravelle et al. (Oncotarget, 2017, vol. 8, No. 27, pp: 44960-44975; hereinafter “Gravelle”) and Krishnan et al. (Am J Surg Pathol 2010;34:178–189; hereinafter “Krishnan”), and US 10,266,593 B2 (hereinafter “US593”) as applied to claim(s) 20, 24, and 26 above, and further in view of US 11,091,541 B2 (hereinafter “US541”).
The teachings of US885, Stamova, and/or US593 as recited above apply for claim(s) 20, 24 and 26.
US885, Stamova, and/or US593 do not expressly teach the anti-PD1/anti-CD3 bsAb administered to treat cancer further comprises IgG1 M252(E/P/R/D), N434L and/or Q438E amino acid substitutions.
Regarding instant claims 33-34, US541 teaches Human FCRN-binding modified bsAbs that increase antibody solubility [e.g., pg. 1, title; col 6, line 13]. US541 teaches antibodies comprising human IgG1 or human IgG4 [e.g., col 9, lines 61-67]. US541 further teaches the M252D [e.g., pg. 48, col 42, line 53], N434L [e.g., pg. 30, col 5, lines 33-38] mutations eliminate or lesson binding, respectively. US541 further teaches Q438 is involved in the interaction between the Fc-region and the FcRn, and embodiments wherein Q438 is altered (substituted) [e.g., col 16, lines 31-46; col 36, lines 23-36].
Further, it would have been obvious to a PHOSITA to modify the modified composition of an anti-PD1/anti-CD3 bsAb for treating hematological cancer of US885, Stamova, and US593 (see above) to include the IgG1 M252(E/P/R/D), N434L and/or Q438E amino acid substitutions as taught by US541, because US885, Stamova and US593 teach an anti-PD1/anti-CD3 bsAb for treating cancer, and US541 teaches Fc region modifications to alter FcRn binding to bsAbs to increase solubility. There is an expectation of success for a PHOPSITA to substitute the modified Fc region as taught by US541 in place of the Fc region of the anti-PD1/anti-CD3 bsAb as taught by US885, Stamova and US593, because US885 teaches multiple Fc region embodiments for bsAbs (see rejection above), and US541 teaches additional Fc region substitutions for bsAbs. This rationale aligns with the principle of simple substitution of one known element for another to obtain predictable results, supporting a conclusion of obviousness (see MPEP § 2141).
Thus, the invention as a whole is prima facie obvious over the references, especially in the absence of evidence to the contrary.
Claim(s) 48-49 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 2022/0185885 A1 (hereinafter “US885”), in view of Stamova et al. (Antibodies 2012, 1, 172-198; hereinafter “Stamova”) as evidenced by Gravelle et al. (Oncotarget, 2017, vol. 8, No. 27, pp: 44960-44975; hereinafter “Gravelle”) and Krishnan et al. (Am J Surg Pathol 2010;34:178–189; hereinafter “Krishnan”), and US 10,266,593 B2 (hereinafter “US593”) as applied to claim(s) 20 above, and further in view of Correnti et al. (Leukemia (2018) 32:1239–1243; hereinafter “Correnti”).
The teachings of US885, Stamova, and/or US593 as recited above apply for claim(s) 20.
US885, Stamova, and/or US593 do not expressly teach that the anti-PD1/anti-CD3 bsAb is administered treat cancer in combination with another cancer immunotherapy drug.
Regarding instant claims 48-49, Correnti teaches Simultaneous multiple interaction T cell engaging (SMITE) bispecific antibodies overcome bispecific T cell engager (BiTE; e.g., a type of bsAb) resistance via CD28 co-stimulation. Correnti further teaches BiTEs for the treatment of hematologic malignancies, and that co-treatment with a CD28 BiTE (e.g., anticancer immunotherapy) enhances anti-tumor efficacy of the CD3 BiTE antibodies [e.g., fig 1].
Further, it would have been obvious to a PHOSITA to modify the modified method of administering anti-PD1/anti-CD3 bsAb to treat hematological cancer of US885, Stamova, and US593 (see above) to include another cancer immunotherapy drug as taught by Correnti, because US885, Stamova and US593 teach a bsAb that is a BiTE for the treatment of hematological cancer (see above), and Correnti teaches BiTEs for the treatment of hematological cancer and that the addition of a co-treatment with a CD28 BiTE enhances the anti-tumor efficacy of the CD3 BiTE. There is an expectation of success for a PHOPSITA to add a CD28 BiTE (second immunotherapy) as taught by Correnti in addition to the anti-PD1/anti-CD3 bsAb administered to treat hematological cancer, because Correnti teaches the addition of a co-treatment with a CD28 BiTE enhances the anti-tumor efficacy of the CD3 BiTE. This rationale aligns with the principle of applying a known technique to a known method to yield predictable results, supporting a conclusion of obviousness (see MPEP § 2143).
Thus, the invention as a whole is prima facie obvious over the references, especially in the absence of evidence to the contrary.
Response to Arguments – 35 USC 103
Applicant argues:
In response to Advisory Action, Examiner failed to address: Gravelle indicates nothing that can be interpreted as corresponding to ‘PD-1 is a known TAA’. Gravelle teaches PDL1 overexpression leads to TIL exhaustion, poor prognosis, and is an effective therapeutic strategy for NHL. Gravelle describes PD1 expressed in some lymphomas merely as supplementary information to the above conclusion, and there is no disclosure in Gravelle that would lead a person skilled in the art to regard PD1 as a TAA and to positively conceive of PD1 as a target molecule. Therefore Examiner did not rebut Gravelle effectively.
Fratricide arguments are erroneous for their reliance on Gravelle’s teachings of PD1 expression on hematological cancers.
In response to (a), briefly, US885, Stamova, and US593 all taught bsAbs for cancer therapy, US885 was relied upon to teach the PD1 arm, Stamova and US593 were used to teach the CD3 arm, Stamova additionally was relied upon to teach the principles and benefits of anti-TAA/anti-CD3 bsAbs in the treatment of cancer, and that TAAs are often selected from hematological cancer TAAs (e.g., PD1 on hematological cancers as evidenced by Gravelle and Krishnan). For clarity of the record, the rejection above recite(s), “PD1 is a known to be expressed on (e.g., a TAA) hematological cancers including peripheral T cell lymphoma, DLBCL, CLL, and HL, as evidenced by…and Krishnan…”. Therefore, Gravelle was relied upon only as an evidentiary reference that PD1 was known in the art to be expressed on a variety of hematological cancers. As discussed in the Advisory Action Responses mailed on 15Apr2026, a skilled artisan would understand that a TAA is a “tumor associated antigen” and therefore any cancer expressed antigen may be considered a TAA. Regarding arguments that PD1 expression in hematological cancers was only a single line in Gravelle, Applicant is reminded that there is no requirement that the limitation(s) appear in more than one line of text within prior art and/or evidentiary references. Additionally, to further demonstrate for the record that PD1 was known in the art to be expressed on heme cancer cells (e.g., not by Gravelle only), Krishnan was additionally relied upon in the current rejection to teach PD1 expression in hematological cancer (see rejection for details). Lastly, the teaching of PDL1 as a therapeutic TAA target for hematological malignancies does not teach away from using PD1 on the cancer cell as the TAA.
In response to (b), no specific arguments were made regarding fratricide, but rather indicated they were improper because Gravelle was improper. Therefore, please see response to argument(s) against Gravelle above.
For the reasons provided above, Applicant arguments have been thoroughly reviewed but are not persuasive. The rejection(s) of claim(s) 20, and 24-49 are maintained in modified form as necessitated by amendment.
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.
Claim(s) 20, 24-32, and 35-47 is/are rejected on the ground of nonstatutory double patenting as being unpatentable over claim(s) 1-6 of U.S. Patent No. 12,325,746 B2 (hereinafter “US746”) in view of US 2022/0185885 A1 (hereinafter “US885”), Stamova et al. (Antibodies 2012, 1, 172-198; hereinafter “Stamova”) as evidenced by Gravelle et al. (Oncotarget, 2017, vol. 8, No. 27, pp: 44960-44975; hereinafter “Gravelle”) and Krishnan et al. (Am J Surg Pathol 2010;34:178–189; hereinafter “Krishnan”), and US 10,266,593 B2 (hereinafter “US593”). Although the claims at issue are not identical, they are not patentably distinct from each other.
The US885 document is the PG Publication for the US746 patent, and therefore all alignments in the 35 USC 103 rejection above also apply for this rejection (see above).
Regarding instant claims 20, 27-32, 35, 40-47, US746 claim 1 teaches an anti-PD1/anti-CD19 bsAb wherein the first arm (anti-PD1) comprises: (a) a VH of SEQ ID NO: 5, which is the same as instant claimed PD1 arm VH SEQ ID NOs: 4-5; and (b) a VL of SEQ ID NO: 25, which is the same as instant claimed PD1 arm VL SEQ ID NO: 25.
Regarding instant claims 24-26, US746 claim 2 teaches the bsAb is an IgG1 antibody.
Regarding instant claim 36, US746 claim 3 teaches the first (PD1) arm comprises a CH of SEQ ID NO: 23.
Regarding instant claim 37, US746 claim 4 teaches the second arm comprises a CH of SEQ ID NO: 24.
Regarding instant claim 38, US746 claim 5 teaches the first and second arms of the bsAb each comprise a CL of SEQ ID NO: 29.
Regarding instant claim 39, US746 claim 6 teaches an anti-PD1/anti-CD19 bsAb wherein (1) the first (PD1 arm) comprises a VH of SEQ ID NO: 5, a CH of SEQ ID NO: 23, a VL or SEQ ID NO: 25, and a CL of SEQ ID NO: 29; and (2) the second arm comprises a CH of SEQ ID NO: 24 and a CL of SEQ ID NO: 29.
US746 does not expressly teach (1) anti-PD1 VH arm instant SEQ ID NOs: 1-3, (2) an anti-PD1/anti-CD3 bsAb, (3) CD3 binding arm sequences, (4) an anti-PD1/anti-CD3 bsAb for treating hematological cancer, wherein the hematological cancer is a diffuse large B cell lymphoma (DLBCL), (m) wherein the hematological cancer is classical Hodgkin lymphoma (HL), or (n) wherein the hematological cancer is chronic lymphocytic leukemia (CLL).
The teachings of US885, Stamova, and US593 as recited in the 35 USC 103 rejection for claims 20, 24-32, and 35-47 apply to this rejection (see above for details).
It would have been prima facie obvious to a person having ordinary skill in the art (PHOSITA) before the effective filing date of the claimed invention to substitute the additional anti-PD1 VH sequences as taught by US885, in place of the anti-PD1 VH sequence taught by US746, in the context of designing an anti-PD1 bsAb. A PHOSITA would have been motivated to substitute the anti-PD1 VH sequences taught by US885 in place of the anti-PD1 VH sequence of the bsAb taught by US746, because US885 is the PG Publication of the US746 patent, and therefore teaches the same subject matter including additional anti-PD1 VH domain sequences. There would have been a reasonable expectation of success for a PHOSITA to substitute the anti-PD1 VH domain sequences taught by US885 with the anti-PD1 VH sequences of the anti-PD1/anti-CD19 bsAb taught by US746 because US885 is the PG Publication of the US746 patent, and therefore teaches the same subject matter including additional anti-PD1 VH domain sequences. This rationale aligns with the principle of simple substitution of one known element for another to obtain predictable results, supporting a conclusion of obviousness (see MPEP § 2141).
Further, it would have been obvious to a PHOSITA to further modify the modified anti-PD1/anti-CD19 bsAb composition of US746 and US885 (see above) to include that the hematological cancer is a diffuse large B cell lymphoma (DLBCL), classical Hodgkin lymphoma (HL), or chronic lymphocytic leukemia (CLL) as taught by US885, Stamova, and US593, for reasons as discussed above in the 35 USC 103 rejection. Further, a PHOSITA would reasonably expect to be able to substitute any and all teachings of the US885 PG Publication for the US746 patent because US885 is the PG Publication of US746 patent. There is an expectation of success for a PHOPSITA to include the further specified modifications taught by taught by US885, Stamova, and US593 for the anti-PD1/anti-CD3 bsAb of US746, because (1) US885 is the PG Publication of US746 and therefore is the same, directly applicable subject matter, and (2) the specific rational for each listed included further modification by US885, Stamova, and/or US593 can be found in the 35 USC 103 rejection above. This rationale aligns with the principle of simple substitution of one known element for another to obtain predictable results, supporting a conclusion of obviousness (see MPEP § 2141).
Thus, the invention as a whole is prima facie obvious over the references, especially in the absence of evidence to the contrary.
Claim(s) 33-34 is/are rejected on the ground of nonstatutory double patenting as being unpatentable over claim(s) 1-6 of U.S. Patent No. 12,325,746 B2 (hereinafter “US746”) in view of US 2022/0185885 A1 (hereinafter “US885”), Stamova et al. (Antibodies 2012, 1, 172-198; hereinafter “Stamova”) as evidenced by Gravelle et al. (Oncotarget, 2017, vol. 8, No. 27, pp: 44960-44975; hereinafter “Gravelle”) and Krishnan et al. (Am J Surg Pathol 2010;34:178–189; hereinafter “Krishnan”), and US 10,266,593 B2 (hereinafter “US593”) as applied to instant claim(s) 20, 24, and 26 above, and further in view of US 11,091,541 B2 (hereinafter “US541”).
The teachings of US746, US885, Stamova, and/or US593 as recited above apply for claim(s) 20, 24 and 26.
US746, US885, Stamova, and/or US593 do not expressly teach that the anti-PD1/anti-CD3 bsAb administered to treat cancer further comprises IgG1 M252(E/P/R/D), N434L and/or Q438E amino acid substitutions.
Regarding instant claims 33-34, US541 teaches Human FCRN-binding modified bsAbs that increase antibody solubility [e.g., pg. 1, title; col 6, line 13]. US541 teaches antibodies comprising human IgG1 or human IgG4 [e.g., col 9, lines 61-67]. US541 further teaches the M252D [e.g., pg. 48, col 42, line 53], N434L [e.g., pg. 30, col 5, lines 33-38] mutations eliminate or lesson binding, respectively. US541 further teaches Q438 is involved in the interaction between the Fc-region and the FcRn, and embodiments wherein Q438 is altered (substituted) [e.g., col 16, lines 31-46; col 36, lines 23-36]. Although the claims at issue are not identical, they are not patentably distinct from each other.
Further, it would have been obvious to a PHOSITA to modify the modified composition of an anti-PD1/anti-CD3 bsAb for treating hematological cancer of US746, US885, Stamova, and US593 (see above) to include the IgG1 M252(E/P/R/D), N434L and/or Q438E amino acid substitutions as taught by US541, because US885, Stamova and US593 teach an anti-PD1/anti-CD3 bsAb for treating cancer, and US541 teaches Fc region modifications to alter FcRn binding to bsAbs to increase solubility. There is an expectation of success for a PHOPSITA to substitute the modified Fc region as taught by US541 in place of the Fc region of the anti-PD1/anti-CD3 bsAb as taught by US746, US885, Stamova and US593, because US885 teaches multiple Fc region embodiments for bsAbs (see above), and US541 teaches additional Fc region substitutions for bsAbs. This rationale aligns with the principle of simple substitution of one known element for another to obtain predictable results, supporting a conclusion of obviousness (see MPEP § 2141).
Thus, the invention as a whole is prima facie obvious over the references, especially in the absence of evidence to the contrary.
Claim(s) 48-49 is/are rejected on the ground of nonstatutory double patenting as being unpatentable over claim(s) 1-6 of U.S. Patent No. 12,325,746 B2 (hereinafter “US746”) in view of US 2022/0185885 A1 (hereinafter “US885”), Stamova et al. (Antibodies 2012, 1, 172-198; hereinafter “Stamova”) as evidenced by Gravelle et al. (Oncotarget, 2017, vol. 8, No. 27, pp: 44960-44975; hereinafter “Gravelle”) and Krishnan et al. (Am J Surg Pathol 2010;34:178–189; hereinafter “Krishnan”), and US 10,266,593 B2 (hereinafter “US593”) as applied to instant claim(s) 20 above, and further in view of Correnti et al. (Leukemia (2018) 32:1239–1243; hereinafter “Correnti”). Although the claims at issue are not identical, they are not patentably distinct from each other.
The teachings of US746, US885, Stamova, and/or US593 as recited above apply for claim(s) 20.
US746, US885, Stamova, and/or US593 do not expressly teach that the anti-PD1/anti-CD3 bsAb is administered treat cancer in combination with another cancer immunotherapy drug.
Regarding instant claims 48-49, Correnti teaches Simultaneous multiple interaction T cell engaging (SMITE) bispecific antibodies overcome bispecific T cell engager (BiTE, e.g., a type of bsAb) resistance via CD28 co-stimulation. Correnti further teaches BiTEs for the treatment of hematologic malignancies, and that co-treatment with a CD28 BiTE (e.g., anticancer immunotherapy) enhances anti-tumor efficacy of the CD3 BiTE antibodies [e.g., fig 1].
Further, it would have been obvious to a PHOSITA to modify the modified method of administering anti-PD1/anti-CD3 bsAb to treat hematological cancer of US746, US885, Stamova, and US593 (see above) to include the that the anti-PD1/anti-CD3 bsAb is administered treat cancer in combination with another cancer immunotherapy drug as taught by Correnti, because US746, US885, Stamova and US593 teach a bsAb that is a BiTE for the treatment of hematological cancer (see above), and Correnti teaches BiTEs for the treatment of hematological cancer and that the addition of a co-treatment with a CD28 BiTE enhances the anti-tumor efficacy of the CD3 BiTE. There is an expectation of success for a PHOPSITA to add a CD28 BiTE (second immunotherapy) as taught by Correnti in addition to the anti-PD1/anti-CD3 bsAb administered to treat hematological cancer, because Correnti teaches the addition of a co-treatment with a CD28 BiTE enhances the anti-tumor efficacy of the CD3 BiTE. This rationale aligns with the principle of applying a known technique to a known method to yield predictable results, supporting a conclusion of obviousness (see MPEP § 2143).
Thus, the invention as a whole is prima facie obvious over the references, especially in the absence of evidence to the contrary.
Claim(s) 20, 24-32, and 35-47 is/are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8, 10, 12-18, 25, 29-36, 38 of copending Application No. 19/198,686 (hereinafter A686), in view of US 2022/0185885 A1 (hereinafter “US885”), in view of Stamova et al. (Antibodies 2012, 1, 172-198; hereinafter “Stamova”) as evidenced by Gravelle et al. (Oncotarget, 2017, vol. 8, No. 27, pp: 44960-44975; hereinafter “Gravelle”) and Krishnan et al. (Am J Surg Pathol 2010;34:178–189; hereinafter “Krishnan”), and US 10,266,593 B2 (hereinafter “US593”). Although the claims at issue are not identical, they are not patentably distinct from each other.
A686 is a continuation of US746, and the SEQ ID NOs are the same. Additionally, US885 is the PG publication of US746, therefore US885 SEQ ID alignments in the 35 USC 103 rejections above are considered to apply (alignments are not provided below, see 103 rejections for details).
Regarding instant claims 20, 39-47, A686 claims 1-7 teaches an anti-PD1/anti-CD19 bsAb wherein: (1) the first (PD1) arm comprises: (i) HCDR1-3 comprising: (a) SEQ ID NOs: 6-8, (b) SEQ ID NOs: 9-11, (c) SEQ ID NOs: 12-14, (d) SEQ ID NOs: 15-17, or (e) SEQ ID NOs: 18-20; and (ii) LCDR1-3 comprising SEQ ID NOs: 26-28. A686 claims 10 and 12-17 teach the PD1 arm comprises a VH of SEQ ID NO: 1, 2, 3, 4, or 5. A686 claim 18 teaches the first (PD1) arm and the second arm comprises a VL of seq ID NO:25. Each SEQ ID NO recited above for A686 are the same sequences as the identical SEQ ID NOs of US885, US746, and the instant claims (see 103 rejections for alignments). A686 claim 38 teaches a method for treating autoimmune disease in a subject in need thereof comprising administering to the subject an effective amount of the anti-PD1/anti-CD19 bsAb.
Regarding instant claims 24-27, 32, 35, A686 claim 25 teaches the bsAb is an IgG; claim 26 teaches the IgG bsAb is an IgG1 or IgG4 antibody; claim 27 teaches the bsAb is an IgG1; and claim 28 teaches the Fc receptor binding is eliminated or reduced.
Regarding instant claim 28, A686 claim 29 teaches in the bsAb each CH has L235G and/or G236R substitutions.
Regarding instant claim 29, A686 claim 30 teaches that the first (PD1) arm has L351K and T366K substitutions and the second arm CH has L351D and L368E substitutions.
Regarding instant claim 30, A686 claim 31 teaches that the first (PD1) arm has L351D and L368E substitutions and the second arm CH has L351K and T366K substitutions.
Regarding instant claim 31, A686 claim 32 teaches that in the bsAb each CH has a K477 deletion.
Regarding instant claims 36-38, A686 claim 33-36 teach the PD1 arm of the bsAb has a CH of SEQ ID NO: 23; the bsAb second arm CH is SEQ ID NO: 24; the first and second arms of the bsAb each comprise the CL of SEQ ID NO: 29 (see 103 rejection for alignments).
A686 does not expressly teach (1) an anti-PD1/anti-CD3 bsAb for treating hematological cancer, (2) CD3 binding arm sequences, or(3) wherein the hematological cancer is a diffuse large B cell lymphoma (DLBCL), (m) wherein the hematological cancer is classical Hodgkin lymphoma (HL), or (n) wherein the hematological cancer is chronic lymphocytic leukemia (CLL).
The teachings of US885, Stamova, and US593 as recited in the 35 USC 103 rejection for claims 20, 24-32, and 35-47 apply to this rejection (see above for details).
It would have been prima facie obvious to a person having ordinary skill in the art (PHOSITA) before the effective filing date of the claimed invention to substitute the method of treating autoimmune disease comprising administering an anti-PD1/anti-CD19 bispecific antibody (bsAb) as taught by A686 and US885, with the method of treating cancer comprising administration of an anti-PD1/anti-CD19 bsAb as taught by US885, in the context of designing and developing an anti-PD1 bsAb for cancer therapy. A PHOSITA would have been motivated to substitute the treatment of cancer as taught by US885 in place of the treatment of autoimmune disease as taught by A686 and US885, because US885 teaches that the same anti-PD1/anti-CD19 bsAbs and further teaches that anti-PD1/anti-CD19 bsAbs were previously reported to treat cancer. There would have been a reasonable expectation of success for a PHOSITA to substitute the treatment of cancer in place of the treatment of autoimmune disease as taught by A686 and US885, because US885 teaches that anti-PD1/anti-CD19 bsAbs were previously reported to treat cancer. This rationale aligns with the principle of simple substitution of one known element for another to obtain predictable results, supporting a conclusion of obviousness (see MPEP § 2141).
It would have been prima facie obvious to a person having ordinary skill in the art (PHOSITA) before the effective filing date of the claimed invention to substitute a CD3 arm as taught by Stamova and US593 in place of the CD19 arm of the bsAb in the modified method of administering an anti-PD1/anti-CD19 bsAb to treat cancer as taught by A686 and US885, in the context of designing and developing an anti-PD1/anti-CD3 bsAb for hematological cancer therapy. A PHOSITA would have been motivated to substitute CD3 arm as taught by Stamova and US593, in place of the CD19 arm of the anti-PD1/anti-CD19 bsAb as taught by A686 and US885, because US885 teaches that anti-PD1/anti-CD19 bsAbs were previously reported to treat cancer, Stamova and US593 teach anti-TAA/CD3 bsAbs to treat cancer, and Stamova teaches that anti-TAA (e.g., anti-PD1 in T cell lymphomas) and anti-CD3 bispecific T cell engagers are effective anti-cancer therapeutics because the CD3 arm activates T cells to kill the cell that is bound by the TAA binding arm (e.g., a cancer cell). There would have been a reasonable expectation of success for a PHOSITA to substitute an anti-PD1/anti-CD3 bsAb for treatment of cancer in place of an anti-PD1/anti-CD19 bsAb for treating cancer as taught by A686 and US885 because US885, Stamova, and US593 all teach bsAbs for treating cancer, and Stamova and US593 teach the well-known in the art bispecific T cell engager approach to activate T cells and direct killing to the cell bound by the anti-TAA arm of the bsAb. Additionally, the bispecific T cell engager approach is unique in that it relies on activating T cells and simultaneously binding (bringing into proximity for killing) cells that express the TAA that the anti-TAA arm binds, which works with both agonist and antagonist anti-TAA binding arms because the mechanism relies on the co-localization of tumor target via TAA binding and T cell while simultaneously activating T cells (via CD3 binding). However, a PHOSITA would recognize that while based on the bispecific T cell engager platform would work with either an agonist or antagonist anti-PD1 arm, that there may be additional benefit of an anti-PD1 agonist arm because activation (agonism) of the PD1 receptor suppresses growth, which in the case of a PD1 TAA would necessarily suppress tumor growth. This rationale aligns with the principle of simple substitution of one known element for another to obtain predictable results, supporting a conclusion of obviousness (see MPEP § 2141). Further, it would have been obvious to a PHOSITA to modify the modified method of treating cancer comprising administering an anti-PD1/anti-CD3 bsAb of US885, Stamova, and US593 (see above) to include the anti-CD3 antigen binding domain sequences as taught by US593, because US885 and Stamova collectively teach an anti-PD1/anti-CD3 bsAb for the treatment of cancer but not the CD3 arm sequence, and US593 teaches the CD3 arm sequence for a bsAb. There is an expectation of success for a PHOPSITA to substitute the CD3 arm sequence taught by US593 in place of the general CD3 bsAb arm as taught by US885 and Stamova, because US885, Stamova, and US593 all teach bsAbs and a CD3 arm of the disclosed bsAbs, and US593 further teaches the sequences required to construct an anti-CD3 binding domain (e.g., a CD3 arm). This rationale aligns with the principle of simple substitution of one known element for another to obtain predictable results, supporting a conclusion of obviousness (see MPEP § 2141).
Further, it would have been obvious to a PHOSITA to modify the modified method administering an anti-PD1/anti-CD3 bsAb to treat hematological cancer of A686, US885, Stamova, and US593 (see above) to include an anti-PD1/anti-CD3 bsAb for treating hematological cancer wherein the hematological cancer is (1) peripheral T cell lymphoma, (2) diffuse large B cell lymphoma (DLBCL), (c) classical Hodgkin lymphoma (HL), or (4) chronic lymphocytic leukemia (CLL) because the anti-PD1 TAA is expressed in peripheral T cell lymphoma, DLBCL, HL, and CLL, as evidenced by Gravelle (see above). Additionally, US885 and Stamova teach bsAbs are used in cancer therapy, and Stamova further teaches that the anti-TAA (e.g., PD1) and anti-CD3 is a bispecific T cell engager which is well known in the art approach to target tumor cells for killing by T cells. There is an expectation of success for a PHOPSITA to substitute the specific hematological cancer indication(s) (e.g., peripheral T cell lymphoma, DLBCL, HL, or CLL) in place of the broad hematological cancer indication treated by an anti-PD1/anti-CD3 bsAb administration as collectively taught by A686, US885, Stamova, and US593, because Stamova teaches bispecific T cell engagers are effective anti-cancer therapies when the bispecific comprises a CD3 arm to activate T cells and an anti-TAA (e.g., PD1), and PD1 is a TAA for peripheral T cell lymphoma, DLBCL, HL and CLL, as evidenced by Gravelle (see above). This rationale aligns with the principle of simple substitution of one known element for another to obtain predictable results, supporting a conclusion of obviousness (see MPEP § 2141).
Thus, the invention as a whole is prima facie obvious over the references, especially in the absence of evidence to the contrary.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim(s) 33-34 is/are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim(s) claims 1-8, 10, 12-18, 25, 29-36, 38 of copending Application No. 19/198,686 (hereinafter A686) in view of US 2022/0185885 A1 (hereinafter “US885”), Stamova et al. (Antibodies 2012, 1, 172-198; hereinafter “Stamova”) as evidenced by Gravelle et al. (Oncotarget, 2017, vol. 8, No. 27, pp: 44960-44975; hereinafter “Gravelle”) and Krishnan et al. (Am J Surg Pathol 2010;34:178–189; hereinafter “Krishnan”), and US 10,266,593 B2 (hereinafter “US593”) as applied to instant claim(s) 20, 24, and 26 above, and further in view of US 11,091,541 B2 (hereinafter “US541”).
The teachings of A686, US885, Stamova, and/or US593 as recited above apply for claim(s) 20, 24 and 26.
A686, US885, Stamova, and/or US593 do not expressly teach that the anti-PD1/anti-CD3 bsAb administered to treat cancer further comprises IgG1 M252(E/P/R/D), N434L and/or Q438E amino acid substitutions.
Regarding instant claims 33-34, US541 teaches Human FCRN-binding modified bsAbs that increase antibody solubility [e.g., pg. 1, title; col 6, line 13]. US541 teaches antibodies comprising human IgG1 or human IgG4 [e.g., col 9, lines 61-67]. US541 further teaches the M252D [e.g., pg. 48, col 42, line 53], N434L [e.g., pg. 30, col 5, lines 33-38] mutations eliminate or lesson binding, respectively. US541 further teaches Q438 is involved in the interaction between the Fc-region and the FcRn, and embodiments wherein Q438 is altered (substituted) [e.g., col 16, lines 31-46; col 36, lines 23-36]. Although the claims at issue are not identical, they are not patentably distinct from each other.
Further, it would have been obvious to a PHOSITA to modify the modified composition of an anti-PD1/anti-CD3 bsAb for treating hematological cancer of A686, US885, Stamova, and US593 (see above) to include the IgG1 M252(E/P/R/D), N434L and/or Q438E amino acid substitutions as taught by US541, because US885, Stamova and US593 teach an anti-PD1/anti-CD3 bsAb for treating cancer, and US541 teaches Fc region modifications to alter FcRn binding to bsAbs to increase solubility. There is an expectation of success for a PHOPSITA to substitute the modified Fc region as taught by US541 in place of the Fc region of the anti-PD1/anti-CD3 bsAb as taught by A686, US885, Stamova and US593, because US885 teaches multiple Fc region embodiments for bsAbs (see above), and US541 teaches additional Fc region substitutions for bsAbs. This rationale aligns with the principle of simple substitution of one known element for another to obtain predictable results, supporting a conclusion of obviousness (see MPEP § 2141).
Thus, the invention as a whole is prima facie obvious over the references, especially in the absence of evidence to the contrary.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim(s) 48-49 is/are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim(s) 1-8, 10, 12-18, 25, 29-36, 38 of copending Application No. 19/198,686 (hereinafter A686) in view of US 2022/0185885 A1 (hereinafter “US885”), Stamova et al. (Antibodies 2012, 1, 172-198; hereinafter “Stamova”) as evidenced by Gravelle et al. (Oncotarget, 2017, vol. 8, No. 27, pp: 44960-44975; hereinafter “Gravelle”) and Krishnan et al. (Am J Surg Pathol 2010;34:178–189; hereinafter “Krishnan”), and US 10,266,593 B2 (hereinafter “US593”) as applied to instant claim(s) 20 above, and further in view of Correnti et al. (Leukemia (2018) 32:1239–1243; hereinafter “Correnti”). Although the claims at issue are not identical, they are not patentably distinct from each other.
The teachings of A686, US885, Stamova, and/or US593 as recited above apply for claim(s) 20.
A686, US885, Stamova, and/or US593 do not expressly teach that the anti-PD1/anti-CD3 bsAb is administered treat cancer in combination with another cancer immunotherapy drug.
Regarding instant claims 48-49, Correnti teaches Simultaneous multiple interaction T cell engaging (SMITE) bispecific antibodies overcome bispecific T cell engager (BiTE; e.g., a type of bsAb) resistance via CD28 co-stimulation. Correnti further teaches BiTEs for the treatment of hematologic malignancies, and that co-treatment with a CD28 BiTE (e.g., anticancer immunotherapy) enhances anti-tumor efficacy of the CD3 BiTE antibodies [e.g., fig 1].
Further, it would have been obvious to a PHOSITA to modify the modified method of administering anti-PD1/anti-CD3 bsAb to treat hematological cancer of A686, US885, Stamova, and US593 (see above) to include the that the anti-PD1/anti-CD3 bsAb is administered treat cancer in combination with another cancer immunotherapy drug as taught by Correnti, because A686, US885, Stamova and US593 teach a bsAb that is a BiTE for the treatment of hematological cancer (see above), and Correnti teaches BiTEs for the treatment of hematological cancer and that the addition of a co-treatment with a CD28 BiTE enhances the anti-tumor efficacy of the CD3 BiTE. There is an expectation of success for a PHOPSITA to add a CD28 BiTE (second immunotherapy) as taught by Correnti in addition to the anti-PD1/anti-CD3 bsAb administered to treat hematological cancer, because Correnti teaches the addition of a co-treatment with a CD28 BiTE enhances the anti-tumor efficacy of the CD3 BiTE. This rationale aligns with the principle of applying a known technique to a known method to yield predictable results, supporting a conclusion of obviousness (see MPEP § 2143).
Thus, the invention as a whole is prima facie obvious over the references, especially in the absence of evidence to the contrary.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims(s) 20, 24-32, and 35-47 is/are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18, 22, 24-33 of U.S. Patent No. US 12,091,461 B2 (hereinafter “US461”), in view of US 2022/0185885 A1 (hereinafter “US885”), Stamova et al. (Antibodies 2012, 1, 172-198; hereinafter “Stamova”) as evidenced by Gravelle et al. (Oncotarget, 2017, vol. 8, No. 27, pp: 44960-44975; hereinafter “Gravelle”) and Krishnan et al. (Am J Surg Pathol 2010;34:178–189; hereinafter “Krishnan”), and US 10,266,593 B2 (hereinafter “US593”). Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding claims 20, 27-32, 40-47, US461 claims 1-7 teach “A bispecific antibody specifically binding to PD1 and CD3 or an antibody fragment thereof, comprising a first arm specifically binding to PD1 and a second arm specifically binding to CD3, wherein the first arm specifically binding to PD1….and wherein the second arm specifically binding to CD3…” and specifically discloses the instant claimed VH and VL CDRs for both the PD1 and CD3 binding arms of the bispecific. US461 claims 8, 10-15, and 17-18 teach the instant claimed first arm PD1 VH domains. US461 claims 9-15 and 17 teach the instant claimed second arm CD3 VH domain. US461 claims 16-18, and 26 teach the instant claimed common VL domain sequence (for PD1 and CD3). US461 claims 31-32 (CH), and 33 (CL) teach the instant claimed constant regions. US461 claim 18 teaches “… PD1 and a second arm specifically binding to CD3, wherein the binding to PD1 with the first arm specifically binding to PD1 is cross-competed (1) by a first arm specifically binding to PD1 having a VH comprising the amino acid sequence set forth in any one selected from SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, and SEQ ID NO: 5; and a VL comprising the amino acid sequence set forth in SEQ ID NO: 25, or (2) by a variable region of a monoclonal antibody specifically binding to PD1 having a VH and a VL that are the same as the bispecific antibody.”.
PD1 VH instant claimed SEQ ID NO: 1 (with HCDR1-3 SEQ ID NOs: 6-8) and US461 VH SEQ ID NO: 1 alignment:
PNG
media_image10.png
316
647
media_image10.png
Greyscale
PD1 VH instant claimed SEQ ID NO: 2 (with HCDR1-3 SEQ ID NOs: 9-11) and US461 VH SEQ ID NO: 2 alignment:
PNG
media_image11.png
313
649
media_image11.png
Greyscale
PD1 VH instant claimed SEQ ID NO: 3 (with HCDR1-3 SEQ ID NOs: 12-14) and US461 VH SEQ ID NO: 3 alignment:
PNG
media_image12.png
311
654
media_image12.png
Greyscale
PD1 VH instant claimed SEQ ID NOs: 4 and 5 (with (identical) HCDR1-3 sequences, SEQ ID NOs: 12-14 and 18-20) and US461 VH SEQ ID NOs: 4 and 5 alignment:
PNG
media_image13.png
440
643
media_image13.png
Greyscale
PD1 and CD3 instant claimed VL (SEQ ID NO: 25; having LCDR1-3 SEQ ID NOs: 26-28) and US461 VL SEQ ID NO: 25 alignment:
PNG
media_image14.png
222
699
media_image14.png
Greyscale
CD3 VH instant claimed SEQ ID NO: 36 (with HCDR1-3 SEQ ID NOs: 37-39) and US461 VH SEQ ID NO: 36 alignment:
PNG
media_image15.png
226
705
media_image15.png
Greyscale
PD1 CH Instant claimed SEQ ID NO: 23 and US461 CH SEQ ID NO: 23 alignment:
PNG
media_image16.png
577
713
media_image16.png
Greyscale
CD3 CH instant claimed SEQ ID NO: 24 and US461 CH SEQ ID NO: 24 alignment:
PNG
media_image17.png
573
721
media_image17.png
Greyscale
PD1 and CD3 CL instant claimed SEQ ID NO: 29 and US461 CH SEQ ID NO: 29 alignment
PNG
media_image18.png
223
707
media_image18.png
Greyscale
Regarding claim 10, US461 claim 7 teaches “…bispecific antibody specifically binding to PD1 and CD3 or antibody fragment thereof….wherein an FRI, an FR2 and an FR3 regions of the VH of the first arm specifically binding to PD1 correspond to an amino acid sequence encoded by a germline V gene IGHV7-4-1 with one or more somatic mutations, and an FR4 region comprises an amino acid sequence encoded by a germ-line J gene JH6c with one or more somatic mutations, excluding 35 the amino acid sequence included in the VH-CDR3 region.
Regarding claims 24-27, 32, US461 claim 22 teaches the bispecific is an IgG antibody, claim 23 teaches the IgG antibody is an IgG1 or an IgG4, claim 24 teaches an IgG1 antibody, and claim 25 teaches the Fc receptor is eliminated or reduced (attenuated).
Regarding claims 28-31, 35, US461 claim 26 teaches “…wherein in two heavy chain constant regions of the PD1/CD3 bispecific IgG1 antibody, leucine at position 235 according to the EU numbering system is substituted with glycine, and/or glycine at position 236 according to the EU numbering system is substituted with arginine.”, claim 27 teaches “…wherein in a constant region of a heavy chain having a VH of the first arm specifically binding to PD1, leucine at position 351 according to the EU numbering system is substituted with lysine, and threonine at position 366 according to the EU numbering system is substituted with lysine; and in a constant region of a heavy chain having a VH of the second arm specifically binding to CD3, leucine at position 351 according to the EU numbering system is substituted with aspartic acid, and leucine at position 368 according to the EU numbering system is substituted with glutamic acid.”, claim 28 teaches “…wherein in a constant region of a heavy chain having a VH of the first arm specifically binding to PD1, leucine at position 351 according to the EU numbering system is substituted with aspartic acid, and leucine at position 368 is substituted with glutamic acid; and in a constant region of a heavy chain having a VH of the second arm specifically binding to CD3, leucine at position 351 according to the EU numbering system is substituted with lysine, and threonine at position 366 according to the EU numbering system is substituted with lysine.”, claim 29 teaches “…wherein in two heavy chain constant regions, lysine at position 447 according to the EU numbering system is deleted.”, claim 30 teaches “…wherein the PD1/CD3 bispecific antibody is an IgG4 antibody, and in two heavy chain constant regions serine at position 228 according to the EU numbering system is substituted with proline.
US461 does not expressly teach (1) an anti-PD1/anti-CD3 bsAb for treating hematological cancer, (2) CD3 binding arm sequences, (3) an anti-PD1/anti-CD3 bsAb for treating hematological cancer (a) wherein the PD1 arm VH FR1/2/3 regions correspond to amino acid sequences encoded by IGHV7-4-4 which may have one or more somatic mutations and FR4 comprises an amino acid sequence encoded by JH6c which may have one or more somatic mutations, (b) wherein the bsAb is an IgG1 antibody wherein the Fc receptor binding is eliminated or attenuated, (c) wherein the bsAb is an IgG1 antibody has L235G and/or G236R substitution(s), (d) wherein the PD1 arm CH has L351K and T366K substitutions and the CD3 arm CH has L351D and L368E substitutions, (e) the PD1 arm has L351D and L368E substitutions and the CD3 arm CH has L351K and T366K substitutions, (f) the two IgG1 CH regions have K447 deleted, (g) wherein the bsAb is an IgG4, wherein the two heavy chain CH regions have S228P substitutions, (h) wherein the PD1 arm VH comprises a CH of SEQ ID NO: 23, (i) wherein the CD3 arm VH comprises a CH of SEQ ID NO: 24, (j) wherein the PD1 and CD3 arms each comprise a VL of SEQ ID NO: 29, (k) wherein the hematological cancer is a peripheral T cell lymphoma, (l) wherein the hematological cancer is a diffuse large B cell lymphoma (DLBCL), (m) wherein the hematological cancer is classical Hodgkin lymphoma (HL), or (n) wherein the hematological cancer is chronic lymphocytic leukemia (CLL).
The teachings of US885, Stamova, and US593 as recited in the 35 USC 103 rejection for claims 3, 5-20, 24-32, and 35-47 apply to this rejection (see above for details).
It would have been prima facie obvious to a person having ordinary skill in the art (PHOSITA) before the effective filing date of the claimed invention to substitute the method of treating autoimmune disease comprising administering an anti-PD1/anti-CD19 bispecific antibody (bsAb) as taught by US461 and US885, with the method of treating cancer comprising administration of an anti-PD1/anti-CD19 bsAb as taught by US885, in the context of designing and developing an anti-PD1 bsAb for cancer therapy. A PHOSITA would have been motivated to substitute the treatment of cancer as taught by US885 in place of the treatment of autoimmune disease as taught by US461 and US885, because US885 teaches that the same anti-PD1/anti-CD19 bsAbs and further teaches that anti-PD1/anti-CD19 bsAbs were previously reported to treat cancer. There would have been a reasonable expectation of success for a PHOSITA to substitute the treatment of cancer in place of the treatment of autoimmune disease as taught by US461 and US885, because US885 teaches that anti-PD1/anti-CD19 bsAbs were previously reported to treat cancer. This rationale aligns with the principle of simple substitution of one known element for another to obtain predictable results, supporting a conclusion of obviousness (see MPEP § 2141).
It would have been prima facie obvious to a person having ordinary skill in the art (PHOSITA) before the effective filing date of the claimed invention to substitute a CD3 arm as taught by Stamova and US593 in place of the CD19 arm of the bsAb in the modified method of administering an anti-PD1/anti-CD19 bsAb to treat cancer as taught by US461 and US885, in the context of designing and developing an anti-PD1/anti-CD3 bsAb for hematological cancer therapy. A PHOSITA would have been motivated to substitute CD3 arm as taught by Stamova and US593, in place of the CD19 arm of the anti-PD1/anti-CD19 bsAb as taught by US461 and US885, because US885 teaches that anti-PD1/anti-CD19 bsAbs were previously reported to treat cancer, Stamova and US593 teach anti-TAA/CD3 bsAbs to treat cancer, and Stamova teaches that anti-TAA (e.g., anti-PD1 in T cell lymphomas) and anti-CD3 bispecific T cell engagers are effective anti-cancer therapeutics because the CD3 arm activates T cells to kill the cell that is bound by the TAA binding arm (e.g., a cancer cell). There would have been a reasonable expectation of success for a PHOSITA to substitute an anti-PD1/anti-CD3 bsAb for treatment of cancer in place of an anti-PD1/anti-CD19 bsAb for treating cancer as taught by US461 and US885 because US885, Stamova, and US593 all teach bsAbs for treating cancer, and Stamova and US593 teach the well-known in the art bispecific T cell engager approach to activate T cells and direct killing to the cell bound by the anti-TAA arm of the bsAb. Additionally, the bispecific T cell engager approach is unique in that it relies on activating T cells and simultaneously binding (bringing into proximity for killing) cells that express the TAA that the anti-TAA arm binds, which works with both agonist and antagonist anti-TAA binding arms because the mechanism relies on the co-localization of tumor target via TAA binding and T cell while simultaneously activating T cells (via CD3 binding). However, a PHOSITA would recognize that while based on the bispecific T cell engager platform would work with either an agonist or antagonist anti-PD1 arm, that there may be additional benefit of an anti-PD1 agonist arm because activation (agonism) of the PD1 receptor suppresses growth, which in the case of a PD1 TAA would necessarily suppress tumor growth. This rationale aligns with the principle of simple substitution of one known element for another to obtain predictable results, supporting a conclusion of obviousness (see MPEP § 2141).
Further, it would have been obvious to a PHOSITA to modify the modified method of treating cancer comprising administering an anti-PD1/anti-CD3 bsAb of US461,US885, Stamova, and US593 (see above) to include the anti-CD3 antigen binding domain sequences as taught by US593, because US461, US885 and Stamova collectively teach an anti-PD1/anti-CD3 bsAb for the treatment of cancer (see above) but not the CD3 arm sequence, and US593 teaches the CD3 arm sequence for a bsAb. There is an expectation of success for a PHOPSITA to substitute the CD3 arm sequence taught by US593 in place of the general CD3 bsAb arm as taught by US461, US885 and Stamova, because US885, Stamova, and US593 all teach bsAbs and a CD3 arm of the disclosed bsAbs, and US593 further teaches the sequences required to construct an anti-CD3 binding domain (e.g., a CD3 arm). This rationale aligns with the principle of simple substitution of one known element for another to obtain predictable results, supporting a conclusion of obviousness (see MPEP § 2141).
Further, it would have been obvious to a PHOSITA to modify the modified composition of an anti-PD1/anti-CD3 bsAb for treating cancer of US461, US885, Stamova, and US593 (see above) to include an anti-PD1/anti-CD3 bsAb for treating hematological cancer (a) wherein the PD1 arm VH FR1/2/3 regions correspond to amino acid sequences encoded by IGHV7-4-4 which may have one or more somatic mutations and FR4 comprises an amino acid sequence encoded by JH6c which may have one or more somatic mutations, (b) wherein the bsAb is an IgG1 antibody wherein the Fc receptor binding is eliminated or attenuated, (c) wherein the bsAb is an IgG1 antibody has L235G and/or G236R substitution(s), (d) wherein the PD1 arm CH has L351K and T366K substitutions and the CD3 arm CH has L351D and L368E substitutions, (e) the PD1 arm has L351D and L368E substitutions and the CD3 arm CH has L351K and T366K substitutions, (f) the two IgG1 CH regions have K447 deleted, (g) wherein the bsAb is an IgG4, wherein the two heavy chain CH regions have S228P substitutions, (h) wherein the PD1 arm VH comprises a CH of SEQ ID NO: 23, (i) wherein the CD3 arm VH comprises a CH of SEQ ID NO: 24, or (j) wherein the PD1 and CD3 arms each comprise a VL of SEQ ID NO: 29 , as taught by US885, because US461, US885, Stamova, and US593 collectively teach the administration of an anti-PD1/anti-CD3 bsAb for the treatment of cancers, and US885 teaches further modifications in the framework region(s) that are applicable for bsAbs. There is an expectation of success for a PHOPSITA to substitute the bsAb framework regions as taught by US885 in order to further modify the modified composition of an anti-PD1/anti-CD3 bsAb for treating cancer of US461, US885, Stamova, and US593 (see above), because US461, US885, Stamova, and US593 all teach bsAbs, and US885 further teaches specific framework regions and modifications thereof for bsAbs. This rationale aligns with the principle of simple substitution of one known element for another to obtain predictable results, supporting a conclusion of obviousness (see MPEP § 2141).
Further, it would have been obvious to a PHOSITA to modify the modified method administering an anti-PD1/anti-CD3 bsAb to treat hematological cancer of US461, US885, Stamova, and US593 (see above) to include an anti-PD1/anti-CD3 bsAb for treating hematological cancer wherein the hematological cancer is (1) peripheral T cell lymphoma, (2) diffuse large B cell lymphoma (DLBCL), (c) classical Hodgkin lymphoma (HL), or (4) chronic lymphocytic leukemia (CLL) because the anti-PD1 TAA is expressed in peripheral T cell lymphoma, DLBCL, HL, and CLL, as evidenced by Gravelle (see above). Additionally, US885 and Stamova teach bsAbs are used in cancer therapy, and Stamova further teaches that the anti-TAA (e.g., PD1) and anti-CD3 is a bispecific T cell engager which is well known in the art approach to target tumor cells for killing by T cells. There is an expectation of success for a PHOPSITA to substitute the specific hematological cancer indication(s) (e.g., peripheral T cell lymphoma, DLBCL, HL, or CLL) in place of the broad hematological cancer indication treated by an anti-PD1/anti-CD3 bsAb administration as collectively taught by US461, US885, Stamova, and US593, because Stamova teaches bispecific T cell engagers are effective anti-cancer therapies when the bispecific comprises a CD3 arm to activate T cells and an anti-TAA (e.g., PD1), and PD1 is a TAA for peripheral T cell lymphoma, DLBCL, HL and CLL, as evidenced by Gravelle (see above). This rationale aligns with the principle of simple substitution of one known element for another to obtain predictable results, supporting a conclusion of obviousness (see MPEP § 2141).
Thus, the invention as a whole is prima facie obvious over the references, especially in the absence of evidence to the contrary.
Claim(s) 33-34 is/are rejected on the ground of nonstatutory double patenting as being unpatentable over claim(s) claims 1-18, 22, 24-33 of U.S. Patent No. US 12,091,461 B2 (hereinafter “US461”) in view of US 2022/0185885 A1 (hereinafter “US885”), Stamova et al. (Antibodies 2012, 1, 172-198; hereinafter “Stamova”) as evidenced by Gravelle et al. (Oncotarget, 2017, vol. 8, No. 27, pp: 44960-44975; hereinafter “Gravelle”) and Krishnan et al. (Am J Surg Pathol 2010;34:178–189; hereinafter “Krishnan”), and US 10,266,593 B2 (hereinafter “US593”) as applied to instant claim(s) 20, 24, and 26 above, and further in view of US 11,091,541 B2 (hereinafter “US541”).
The teachings of US461, US885, Stamova, and/or US593 as recited above apply for claim(s) 20, 24 and 26.
US461, US885, Stamova, and/or US593 do not expressly teach that the anti-PD1/anti-CD3 bsAb is administered to treat hematological cancer further comprises IgG1 M252(E/P/R/D), N434L and/or Q438E amino acid substitutions.
Regarding instant claims 33-34, US541 teaches Human FCRN-binding modified bsAbs that increase antibody solubility [e.g., pg. 1, title; col 6, line 13]. US541 teaches antibodies comprising human IgG1 or human IgG4 [e.g., col 9, lines 61-67]. US541 further teaches the M252D [e.g., pg. 48, col 42, line 53], N434L [e.g., pg. 30, col 5, lines 33-38] mutations eliminate or lesson binding, respectively. US541 further teaches Q438 is involved in the interaction between the Fc-region and the FcRn, and embodiments wherein Q438 is altered (substituted) [e.g., col 16, lines 31-46; col 36, lines 23-36]. Although the claims at issue are not identical, they are not patentably distinct from each other.
Further, it would have been obvious to a PHOSITA to modify the modified composition of an anti-PD1/anti-CD3 bsAb for treating hematological cancer of US461, US885, Stamova, and US593 (see above) to include the IgG1 M252(E/P/R/D), N434L and/or Q438E amino acid substitutions as taught by US541, because US885, Stamova and US593 teach an anti-PD1/anti-CD3 bsAb for treating cancer, and US541 teaches Fc region modifications to alter FcRn binding to bsAbs to increase solubility. There is an expectation of success for a PHOPSITA to substitute the modified Fc region as taught by US541 in place of the Fc region of the anti-PD1/anti-CD3 bsAb as taught by US461, US885, Stamova and US593, because US885 teaches multiple Fc region embodiments for bsAbs (see above), and US541 teaches additional Fc region substitutions for bsAbs. This rationale aligns with the principle of simple substitution of one known element for another to obtain predictable results, supporting a conclusion of obviousness (see MPEP § 2141).
Thus, the invention as a whole is prima facie obvious over the references, especially in the absence of evidence to the contrary.
Claim(s) 48-49 is/are rejected on the ground of nonstatutory double patenting as being unpatentable over claim(s) 1-18, 22, 24-33 of U.S. Patent No. US 12,091,461 B2 (hereinafter “US461”) in view of US 2022/0185885 A1 (hereinafter “US885”), in view of Stamova et al. (Antibodies 2012, 1, 172-198; hereinafter “Stamova”) as evidenced by Gravelle et al. (Oncotarget, 2017, vol. 8, No. 27, pp: 44960-44975; hereinafter “Gravelle”) and Krishnan et al. (Am J Surg Pathol 2010;34:178–189; hereinafter “Krishnan”), and Krishnan et al. (Am J Surg Pathol 2010;34:178–189; hereinafter “Krishnan”), and US 10,266,593 B2 (hereinafter “US593”) as applied to instant claim(s) 20 above, and further in view of Correnti et al. (Leukemia (2018) 32:1239–1243; hereinafter “Correnti”). Although the claims at issue are not identical, they are not patentably distinct from each other.
The teachings of US461, US885, Stamova, and/or US593 as recited above apply for claim(s) 20.
US461, US885, Stamova, and/or US593 do not expressly teach that the anti-PD1/anti-CD3 bsAb is administered treat cancer in combination with another cancer immunotherapy drug.
Regarding instant claims 48-49, Correnti teaches Simultaneous multiple interaction T cell engaging (SMITE) bispecific antibodies overcome bispecific T cell engager (BiTE; e.g., a type of bsAb) resistance via CD28 co-stimulation. Correnti further teaches BiTEs for the treatment of hematologic malignancies, and that co-treatment with a CD28 BiTE (e.g., anticancer immunotherapy) enhances anti-tumor efficacy of the CD3 BiTE antibodies [e.g., fig 1].
Further, it would have been obvious to a PHOSITA to modify the modified method of administering anti-PD1/anti-CD3 bsAb to treat hematological cancer of US461, US885, Stamova, and US593 (see above) to include the that the anti-PD1/anti-CD3 bsAb is administered treat cancer in combination with another cancer immunotherapy drug as taught by Correnti, because US461, US885, Stamova and US593 teach a bsAb that is a BiTE for the treatment of hematological cancer (see above), and Correnti teaches BiTEs for the treatment of hematological cancer and that the addition of a co-treatment with a CD28 BiTE enhances the anti-tumor efficacy of the CD3 BiTE. There is an expectation of success for a PHOPSITA to add a CD28 BiTE (second immunotherapy) as taught by Correnti in addition to the anti-PD1/anti-CD3 bsAb administered to treat hematological cancer, because Correnti teaches the addition of a co-treatment with a CD28 BiTE enhances the anti-tumor efficacy of the CD3 BiTE. This rationale aligns with the principle of applying a known technique to a known method to yield predictable results, supporting a conclusion of obviousness (see MPEP § 2143).
Thus, the invention as a whole is prima facie obvious over the references, especially in the absence of evidence to the contrary.
Response to Arguments – for All NSDP Rejections
Applicant argues:
With respect to the provisional NSDP rejections, Applicant respectfully requests that the Examiner hold the rejections in abeyance until otherwise allowable subject matter is identified.
With respect to the remaining double patenting rejections, Applicant submits that the present claims are patentable over the cited claims and references for at least the reasons set forth above with respect to the rejections under 35 U.S.C. § 103.
Please see the response to arguments under 35 USC 103 above for details regarding response(s) to “b” above. Applicant arguments have been thoroughly reviewed but are not persuasive. Therefore, all of the previous NSDP rejection(s) of claim(s) 20, 24-49 are maintained in modified form as necessitated by amendment.
Conclusion
No claims are currently allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMY M CHATTIN whose telephone number is (571)270-0646. The examiner can normally be reached T-F 0600-1600 PST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Julie Wu can be reached at (571) 272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/AMY M. CHATTIN/Examiner, Art Unit 1643
/JULIE WU/Supervisory Patent Examiner, Art Unit 1643
Prosecution Insights