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 .
Claims Status
The amendments and remarks filed 05/01/2026 are acknowledged.
Claims 1-4, 6, 10-14, 16, 24, 26, 28, 39, 53-55, 57-59, 61, and 63-64 are pending.
Claims 10, 12, and 28 are amended.
Claims 5, 7-9, 15, 17-23, 25, 27, 29-38, 40-52, 56, 60, and 62 are canceled.
Claims 63 and 64 are new.
Claims 59 and 61 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 08/19/2025.
Therefore, claims 1-4, 6, 10-14, 16, 24, 26, 28, 39, 53-55, 57-58, and 63-64 are under examination.
Withdrawn
The objection to the specification is withdrawn. Applicant has submitted a substitute specification to overcome this objection.
The rejections of claims 10, 12, and 28 under 35 U.S.C. 112(b) are withdrawn. Applicant has amended the claims to overcome the rejections.
Maintained Rejections
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.
This rejection has been modified solely to address new claims 63 and 64.
Claims 1-4, 6, 10-14, 16, 24, 26, 28, 39, 53-55, 57-58, and 63-64 are rejected under 35 U.S.C. 103 as being unpatentable over Polson (US 20160082120) and further in view of NCT01670370 (2018; instant PTO-892).
Regarding claims 1, 6, 10-13, 16, and 57-58, Polson teaches a method for treating a B-cell proliferative disorder, in particular Diffuse Large B-cell Lymphoma (DLBCL), by administering to an individual an effective amount of an immunoconjugate comprising an anti-CD79b antibody linked to a cytotoxic agent and rituximab [0003, 0008-0009, Claims 1-2]. Polson also teaches that the formula of the immunoconjugate is [0016]:
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This structure is 100% identical to the structure of the instant claim, and therefore, this structure is necessarily polatuzumab vedotin-piiq (as elected). Additionally, Polson teaches administering polatuzumab vedotin (anti-CD79b (huMA79b.v8)-MC-vc-PAB-MMAE), which has the same structure as polatuzumab vedotin-piiq, in combination with rituximab in patients with relapsed or refractory diffuse large B-cell lymphoma [0422]. Polson further teaches that the antibody comprises (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO:21; (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO:22; (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO:23; (d) HVRL1 comprising the amino acid sequence of SEQ ID NO:24; (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO:25; and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO:26 [0019].
SEQ ID NOs: 21-26 have 100% sequence identity to SEQ ID NOs: 21-26 of the instant claim, respectively.
Polson further teaches that p ranges from 1-8 [0012] and that the anti-CD79b immunoconjugate demonstrated clear inhibition of tumor growth and the combination with rituximab resulted in significantly greater efficacy [0421]. Polson also teaches that the anti-CD79 immunoconjugate (polatuzumab vedotin-piiq) is administered at a dose of 1.8 mg/kg [0158], the rituximab is administered at a dose of 375 mg/m2 [0159], and that the anti-CD79b immunoconjugate (polatuzumab vedotin-piiq) and the additional therapeutic agent (rituximab) can be co-administered on the same day [0155]. Polson further teaches that polatuzumab vedotin (anti-CD79b immunoconjugate) is administered intravenously in combination with rituximab, and rituximab is administered on day 1 of cycle 1 and on day 1 of each subsequent cycle for up to 6 cycles [0424]. Polson also teaches polatuzumab vedotin 1.8 mg/kg is administered intravenously (IV) on day 1 of cycle 1-6 of each 21-day cycle [0457-0463]. Polson further teaches Rituximab may be administered up to nine 3- to 4- weeks-dosage-cycles [0159] and that the dosing regimens for administration of the combination therapy of the anti-CD79b immunoconjugate and rituximab are, but not limited to, every 3 weeks (21 day cycle) [0160]. This range overlaps with up to eight 21-day cycles. MPEP 2144.05 (I) states “in the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facia case of obviousness exists”.
However, Polson does not specifically teach administering an effective amount of (c) gemcitabine, and (d) oxaliplatin in combination with (a) the immunoconjugate and (b) rituximab, or that gemcitabine is administered at a dose of 1000 mg/m2, the oxaliplatin is administered at a dose of 100 mg/m2, and that the immunoconjugate (polatuzumab vedotin-piiq), the rituximab, the gemcitabine, and the oxaliplatin are administered for at least one (i.e. one or more) 21-day cycles, and wherein the gemcitabine and oxaliplatin are administered intravenously on Day 2 of each 21-day cycle.
NCT01670370 teaches R-GemOx, a combination of Rituximab, Gemcitabine, and Oxaliplatin to treat DLBCL [page 3]. NCT01670370 further teaches that Rituximab is administered at 375 mg/m2 IV (intravenously) on day 1, Gemcitabine is administered at 1g/m2 (equivalent to 1000mg/m2) IV (intravenously) on day 2, and Oxaliplatin is administered at 100mg/m2 IV (intravenously) on day 2 [page 4]. NCT01670370 also teaches that R-GemOx achieved high efficacy with a low toxicity profile in relapsed and refractory DLBCL [page 4].
It would have been obvious to someone of ordinary skill in the art before the effective filing date of the claimed invention to have combined the anti-CD79b immunoconjugate (polatuzumab vedotin-piiq) and rituximab, as taught by Polson, with the gemcitabine, and oxaliplatin, as taught by NCT01670370. One would have been motivated to combine these therapies because all are known compositions to treat diffuse large B-cell lymphoma (DLBCL) and relapsed or refractory (R/R) DLBCL. MPEP 2144.06 states “it is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). Therefore, it would have been obvious to combine the separate, known compositions into one single composition for the same purpose of treating DLBCL and R/R DLBCL with a reasonable expectation of success.
It further would have been obvious to someone of ordinary skill in the art before the effective filing date of the claimed invention to administer the Polatuzumab vedotin (immunoconjugate) at a dose of 1.8mg/kg, as taught by Polson, the rituximab at a dose of 375 mg/m2, as taught by Polson and NCT01670370, the gemcitabine at a dose of 1000 mg/m2, as taught by NCT01670370, and the oxaliplatin at a dose of 100mg/m2, as taught by NCT01670370, for one or more 21-day cycles, for up to 9 cycles, as taught by Polson, wherein the immunoconjugate and the rituximab are administered intravenously on Day 1, as taught by Polson, and the gemcitabine and the oxaliplatin are administered intravenously on Day 2, as taught by NCT01670370, because these are known values of known parameters in the art, and therefore would have a reasonable expectation of success.
Claim 2 is included in this rejection because Polson teaches that the
antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 19 and a VL sequence comprises the amino acid sequence of SEQ ID NO:20 [0020].
SEQ ID NO: 19 has 100% identity to SEQ ID NO: 19 of the instant claim and SEQ ID NO: 20 has 100% identity to SEQ ID NO: 20 of the instant claim.
Claim 3 is included in this rejection because Polson teaches that the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:36 and a light chain comprising the amino acid sequence of SEQ ID NO:35 [0020].
SEQ ID NO: 36 has 100% identity to SEQ ID NO: 36 of the instant claim and SEQ ID NO: 35 has 100% identity to SEQ ID NO: 35 of the instant claim.
Claim 4 is included in this rejection because Polson teaches that p ranges from 1-8 [0012] and in some embodiments p ranges from 2-5 [0017]. MPEP 2144.05 (I) states “in the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facia case of obviousness exists”.
Claim 14 is included in this rejection because Polson teaches that the anti-CD79b immunoconjugate and the additional therapeutic agents are co-administered either simultaneously or sequentially in either order and when both therapeutic agents are co-administered sequentially the dose can be administered in two separate administrations [0155]. Further, rearranging steps is not inventive. See MPEP 2144 (IV)(C) which cites In re Burhans, 154 F.2d 690, 69 USPQ 330 (CCPA 1946) that states “selection of any order of performing process steps is prima facie obvious in the absence of new or unexpected results.”
Claim 24 is included in this rejection because Polson teaches that the individual has received at least one prior therapy for DLBCL [0149].
Claim 26 is included in this rejection because Polson teaches that the B-cell proliferative disorder is a histologically confirmed DLBCL [0149] and the B-cell proliferative disorder is a relapsed or refractory B-cell proliferative disorder [0151].
Claim 28 is included in this rejection because NCT01670370 teaches that the inclusion criteria for patients is to be newly-diagnosed and untreated. Therefore, the human would not have (f) had prior therapy with a combination of gemcitabine and a platinum-based agent or (g) received a prior therapy with polatuzumab vedotin-piiq for DLBCL.
Claims 39 and 53 are included in this rejection because it merely recites effects or results of administering the immunoconjugate, the rituximab, the gemcitabine, and the oxaliplatin together. Because it would have been obvious to administer this combination as described above, a person of ordinary skill in the art would have reasonably expected these effects to occur, absent evidence to the contrary. Further (a) and (b) are properties of the combination of the immunoconjugate, the rituximab, the gemcitabine, and the oxaliplatin. Applicant is reminded that chemical compounds and their properties are inseparable (In re Papesch, 315 F.2d 381, 137 USPQ 43 (CCPA1963)), as are their processes and yields (In re Von Schickh, 362 F.2d 821, 150 USPQ 300 (CCPA 1966)).
Claims 54 and 55 are included in this rejection because Polson teaches an article of manufacture containing materials for the treatment of DLBCL, wherein the article of manufacture (kit) comprises a container and a label or package insert on or associated with the container, and wherein the container holds a composition which is by itself or container with another composition effective for treating , and that the composition is the immunoconjugate of the invention. Polson further teaches that the article of manufacture may comprise a first container with a composition contained therein, wherein the composition comprises the immunoconjugate and a second container with a composition contained therein, wherein the composition comprises a further cytotoxic or otherwise therapeutic agent [0415].
The limitation of “for use in combination with rituximab, gemcitabine, and oxaliplatin for treating a human in need thereof having diffuse large B-cell lymphoma (DLBCL) according to the method of claim 1” is a recitation of intended use. The recitation of the intended use does not result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. As taught above, the prior art structure (i.e. polatuzumab vedotin-piiq) is capable of performing the intended use, and thus, it meets the limitations of the instant claims.
Claim 63 is included in this rejection because NCT01670370 teaches that the minimum age for the eligibility of patients in this study is 60 years (an adult) [page 5].
Claim 64 is included in this rejection because Polson teaches administering
polatuzumab vedotin (anti-CD79b (huMA79b.v8)-MC-vc-PAB-MMAE), which has the
same structure as polatuzumab vedotin-piiq), in combination with rituximab in patients
with relapsed or refractory diffuse large B-cell lymphoma [0422].
Response to Arguments
The rejections under 35 U.S.C. 103 over Polson and NCT01670370 are maintained. On page 12 of the remarks, Applicant argues that the Examiner has not provided a sufficient rational to combine the agents of Polson with those of NCT01670370, citing MPEP 2145(X) that “contrary to accepted wisdom in the art is evidence of nonobviousness”, and that the totality of the prior art and accepted wisdom in the art teach away from a method of treatment comprising administration of an anti-CD79b immunoconjugate (i.e. polatuzumab vedotin), rituximab, gemcitabine, and oxaliplatin because it was known at the time the present application was filed that polatuzumab vedotin and oxaliplatin were each associated with neurotoxicity. Applicant supports this argument by citing the teachings of Cohen and Pulvers and Marks, which teach that polatuzumab vedotin and oxaliplatin were each known to be toxic on their own. This is not found persuasive because Applicant is comparing to what may have been expected from separate references showing only 2 of the 4 drugs claimed when administered separately. Further, the art Applicant cites is not the closest prior art at the time the application was filed and even though Applicant argues that two of the drugs were individually toxic, the art also still explicitly teaches combining these drugs. The closest prior art is the art cited in the office action, i.e. Polson and NCT01670370, which each teach that combining the respective drugs is more effective than individual treatments. Polson teaches that a triple combination with an anti-CD79b antibody drug conjugate, rituximab, and bendamustine resulted in significantly greater efficacy than the antibody drug conjugate or rituximab/bendamustine doublet alone [0421]. Additionally, NCT01670370 teaches that the combination of rituximab, gemcitabine, and oxaliplatin achieved high efficacy with a low toxicity profile in relapsed and refractory DLBCL [page 3, see Detailed Description]. Furthermore, Bendamustine and Oxaliplatin are both chemotherapy drugs that are alkylating agents [see Mayo Clinic, and see Chemocare]. In view of these teachings, a person of ordinary skill in the art would have been motivated to combine the teachings of Polson and NCT01670370 with a reasonable expectation of success of treating DLBCL.
On page 13 of the remarks, Applicant argues that one would not have been reasonably motivated to have combined the teachings of Polson and NCT01670370 because the prior art as a whole would have suggested to one of ordinary skill in the art that the combination of both polatuzumab vedotin and oxaliplatin was likely to result in an increased and cumulative risk of peripheral neuropathy, and thus, the art teaches away from a method comprising administration of polatuzumab vedotin, rituximab, gemcitabine, and oxaliplatin. This is not found persuasive because a teaching away must criticize, discredit, or otherwise discourage [see MPEP 2143.01(I)], and even if Applicant’s argument that combining the CD79b immunoconjugate with oxaliplatin would result in increased and cumulative risk of neurotoxicity is true, the art clearly still teaches that these are effective chemotherapeutics. There is no evidence that the person of ordinary skill in the art would consider this alleged “increased risk” sufficient to avoid combining two known effective treatments. Further, Applicant has not provided any evidence that a person of ordinary skill in the art would consider this alleged “risk” of peripheral neuropathy sufficient to avoid combining the effective treatments. Applicant is reminded that “arguments of counsel cannot take place of factually supported objective evidence” (see MPEP §2145).
On pages 14-15 of the remarks, Applicant argues that the combination of polatuzumab vedotin, rituximab, gemcitabine, and oxaliplatin (Pola-R-GemOx), as claimed, demonstrates an unexpectedly high degree of efficacy as compared to a combination treatment with only rituximab, gemcitabine, and oxaliplatin (R-GemOx), as allegedly taught by NCT01670370, resulting in an increase in overall survival, progression-free survival, complete response rate, objective response rate, best overall response, and event-free survival, further arguing that this unexpectedly high degree of efficacy was not demonstrated by either Polson and NCT01670370, and thus, could not have been reasonably predicted by one of ordinary skill in the art. This is not found persuasive because Applicant does not demonstrate the results of polatuzumab vedotin when administered alone. Therefore, the Examiner cannot make a determination of a trend that would lead to a conclusion of unexpected results. The burden is on Applicant to provide the Examiner a trend proving the unexpected results. See MPEP 716.02(b). In view of the above, Applicant’s arguments of unexpected results are not persuasive to rebut the rejections under 35 U.S.C. 103.
Conclusion
No claims are 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 nonprovisional extension fee (37 CFR 1.17(a)) 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 mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Brittney E Donoghue whose telephone number is (571)272-9883. The examiner can normally be reached Mon - Fri 7:30 - 3:30.
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/B.E.D./Examiner, Art Unit 1675
/JEFFREY STUCKER/Supervisory Patent Examiner, Art Unit 1675
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