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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 11/04/2025 has been entered.
Claims Status
Claims 32, 36, 44-45, 50, 52, and 54-55 are cancelled.
Claims 129-130 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 08/24/2024.
Claims 1-2, 12-13, 15, 22, 24, 62, 72-73, 75, 84, 88-90, 97, 99-100, and 128 are pending and are examined on the merits.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-2, 62, 72-73, 75, 84, 88-90, 97, 99-100, and 128 are rejected under 35 U.S.C. 102(a)(1) as anticipated by Tilly et al. 2019 (The Lancet Oncology, 20(7), 998-1010.; of record), herein “Tilly”, as evidenced by “The 2016 revision of the World Health Organization classification of lymphoid neoplasms” (Swerdlow et al. 2016. Blood, 127(20), 2375-2390.; PTO-892), Sehn et al. 2020 (Journal of hematology & oncology, 13(1), 71.; PTO-892), and the instant specification.
Tilly teaches a method of treating diffuse large B-cell lymphoma (DLBCL), including those of the activated B-cell (ABC) and germinal center B-cell (GCB) subtypes (Table 1), comprising six to eight 21-day cycles comprising IV administration of 750 mg/m2 cyclophosphamide, 50 mg/m2 doxorubicin, 375 mg/m2 rituximab, and 1.8 mg/kg polatuzumab vedotin on day 1 of each cycle and oral administration of 100 mg prednisone daily for days 1-5 of each cycle (Pg. 1000, § Procedures; Supplemental Protocol §4.3.2 Dosage, Administration, and Compliance).
Regarding the new limitation of the amended claims wherein the DLBCL is “a DLBCL, not otherwise specified (NOS)”, GCB and ABC DLBCL are both subtypes of “DLBCL, not otherwise specified (NOS)”, as evidenced by the 2016 revision of the World Health Organization classification of lymphoid neoplasms (Blood, 127(20), 2375-2390.; see Tables 1-2; Pg. 2380) and the instant specification (e.g. ¶0323: “...DLBCL, not otherwise specified (NOS), including germinal center B-cell type, activated B-cell type;...”).
Regarding instant Claims 2, Tilly teaches that disease progression is measured from the date of the first dose to the first occurrence of progression (Supplemental Protocol Pg. 19, § Activity Outcome Measures).
Regarding instant Claims 97 and 99-100, Tilly teaches that prophylaxis for tumor lysis syndrome includes a hydration regimen of 3 L/day starting 1 or 2 days before the first study dose and 300 mg/day allopurinol starting 48-72 hours before Cycle 1 (Supplemental Protocol §5.1.7.1).
Regarding instant Claim 128, Tilly teaches that disease progression, including death from any cause, is assessed using the 2014 Lugano Response Criteria (Supplemental Protocol §3.4.3; Appendix 3).
Tilly teaches that a higher proportion of patients receiving pola-R-CHP achieved a complete response (CR) and progression-free survival (PFS) at one year when compared to the control group of the contemporary “GOYA” trial (i.e. a “reference PFS”), despite a higher proportion of enrolled patients having characteristics prognostic for poor outcomes (Pg. 1009, ¶2-3). As evidenced by Sehn, the control group of GOYA were treated with the standard of care “R-CHOP” comprising a combination of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (Abstract).
Claim Rejections - 35 USC § 102/103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 12-13, 15, 22, and 24 are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Tilly et al. 2019 (The Lancet Oncology, 20(7), 998-1010.; of record), herein “Tilly”, as evidenced by “The 2016 revision of the World Health Organization classification of lymphoid neoplasms” (Swerdlow et al. 2016. Blood, 127(20), 2375-2390.; PTO-892), Sehn et al. 2020 (Journal of hematology & oncology, 13(1), 71.; PTO-892), and the instant specification.
The teachings of Tilly are summarized above.
Tilly does not teach several of the particular outcomes/results recited in the claims including time-to-event metrics (e.g. Claims 12-13) and hazard ratios (e.g. Claim 15, 24).
However, as summarized above, Tilly discloses a method of treating DLBCL NOS with a modified R-CHP regimen wherein vincristine is substituted with polatuzumab vedotin (“Pola-R-CHP”) – a method comprising the same therapeutics administered at the same doses according to the same schedule to the patients having the same disease as instantly claimed. Accordingly, any outcomes achieved in practicing the Pola-R-CHP method of Tilly are inherent to said method necessarily flow from its practice.
Indeed, results disclosed in the instant specification (e.g. Fig. 15, Fig. 27) demonstrate as much – i.e. DLBCL patients receiving the Pola-R-CHP regimen as disclosed by Tilly achieved at least a 20% reduction in risk of disease progression and an unstratified hazard of about 0.77 as compared to control. Such outcomes are therefore inherent to the method of the prior art, and they need not have previously noticed for the method of the instant claims to be anticipated by the Pola-R-CHP protocol taught by Tilly. See MPEP §2112 (e.g. “I. Something which is old does not become patentable upon the discovery of a new property” and “II. Inherent feature need not be recognized at the relevant time”).
Moreover, the recited outcome measures of the method according to the claims do not confer any features that would distinguish its practice from that of the method taught by Tilly (e.g. active steps, additional therapeutics, etc.). Even without knowledge said results, one of ordinary skill in the art would remain motivated by the teachings of Tilly to employ the Pola-R-CHP regimen to treat DLBCL NOS. There would have been a reasonable expectation of success because Tilly teaches that the preliminary results from the Pola-R-CHP Phase II trial compared favorably to the standard-of-care in a separate contemporary trial in spite of a high proportion of enrolled patients having characteristics prognostic for poor outcomes, and that “the proportion of patients with a response and with progression-free survival were similar across the biological subsets of diffuse large B-cell lymphoma” (Pg. 1009).
Response to Arguments
Applicant's arguments filed 11/04/2025 have been fully considered but they are not persuasive because:
First, Applicant argues the claims as amended “specify a patient subgroup that is not disclosed in Tilly”. However, as discussed above, Tilly teaches treatment of ABC and GBC type DLBCL, both of which belong to the claimed subgroup of “DLBCL, not otherwise specified (NOS)” – a fact acknowledged in the instant specification (e.g. ¶0323). Accordingly, the instant claims remain anticipated by Tilly.
Applicant further argues that the therapeutic effects of the claims are not inherent to practice of the Pola-R-CHP regimen of Tilly (Remarks, Pg. 28, last ¶). Applicant asserts that because Tilly discloses differences in response between DLBCL subtypes and that some – but not all – patients achieved an overall response when treated with the Pola-R-CHP regimen that the claimed results are not “inextricably linked to” nor “the natural result of” the method taught by Tilly.
In response it is noted that the instant Claims are not drawn to a method having 100% efficacy but instead claim a method having particular population-level responses among a plurality of treated patients. The teachings of Tilly are consistent with the claims and instant disclosure in this regard, each demonstrating efficacy of the Pola-R-CHP regimen in a majority, but not totality, of patients treated. Moreover, as stated above, the Pola-R-CHP protocol of Tilly is identical to that of the instant disclosure, Tilly demonstrates broad efficacy of said method among the DLBCL NOS subtype, and the particular population-level outcome measures encompassed by the instant claims do not materially alter how said method is performed.
Finally, regarding applicant’s assertion that “the claimed methods are based on unexpected results” (Remarks, Pg. 29, ¶3), it is first noted that only instant Claims 73 and 90 specify the complete protocol used to achieve the disclosed results (particular doses, schedule, etc.), however neither claim requires these limitations as they are claimed in the alternative (“and/or”) with the control treatment recited thereafter. As such, none of the instant claims is commensurate in scope with the method purported to have produced “unexpected results”.
Moreover, the results disclosed in the instant application would neither be surprising nor unexpected to one of ordinary skill in the art familiar with the disclosure of Tilly. Tilly highlights that, despite disproportionately unfavorable patient characteristics of those enrolled, the Pola-R-CHP regimen resulted in greater levels of complete response and progression free survival when compared to the control group of the contemporary GOYA trial. In fact, the prior art supports such this very comparison for exploratory analysis. For example, Morschhauser et al. 2021 (Blood. 137.5 (2021): 600-609.; of record) teaches that R-CHOP controls from the recent GOYA trial are “statistically robust and clinically meaningful” (Pg. 602) and can serve as an “appropriate contemporary benchmark for safety and efficacy” (Abstract).
While Tilly concedes that the Phase II trial reported on “is not a randomized study designed to enable comparison”, Tilly ultimately concludes: “[h]owever, the activity observed is promising, particularly in the context of high-risk patients, in terms of both patient risk and biological disease characteristics”. Accordingly, in view of the extensive foundation of reliable data from the long-practiced R-CHP regimen combined with the promising early response rates reported by Tilly, the results of the follow-up phase 3 trial as disclosed in the instant application would not have been particularly surprising to one of ordinary skill in the art.
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.
Claims 1-2, 15, 22, 24, 62, 72-73, 75, 84, 88-90, and 97 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5, 9-10, 15, 24, 31, 72-76, 80, 87, 89-91, and 118 of copending Application No. 18/681,787 (US 2024/0336697 A1; of record). Although the claims at issue are not identical, they are not patentably distinct from each other because:
The claims of ‘787 are drawn to a method of treating diffuse large B-cell lymphoma (DLBCL) comprising administering 1.8 mg/kg polatuzumab vedotin, 375 mg/m2 rituximab, 750 mg/m2 cyclophosphamide, 50 mg/m2 doxorubicin, and 100 mg prednisone wherein progression free survival (PFS) is extended relative to a reference PFS from a plurality of patients who have received a control treatment comprising rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone in the absence of polatuzumab vedotin.
The claims of ‘787 are further drawn to administering said method on according to 21-day cycles, wherein polatuzumab vedotin, rituximab, cyclophosphamide, and doxorubicin are administered on day 1 of each cycle, and predinisone is administered on each of days 1-5 of each cycle – and wherein the prednisone is administered prior to the rituximab, the rituximab is administered prior to the polatuzumab vedotin, and the polatuzumab vedotin is administered prior to the cyclophosphamide.
The claims of ‘787 are further drawn to a variety of patient populations including patients that have high grade lymphoma, have an IPI score between 3 and 5, ECOG performance status of 0-2, does not have a demyelinating form of Charcot-Marie Tooth disease, etc.
The claims of ‘787 are further drawn to the method wherein PFS is measured from the start of treatment to the first occurrence of disease progression, wherein PFS improvement is statistically significant with a hazard ratio of no more than 0.4, and wherein the hazard ratio is calculated at 12 or 24 months.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 12-13, 99-100, and 128 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5, 9-10, 15, 24, 31, 72-76, 80, 87, 89-91, and 118 of copending Application No. 18/681,787, and further in view of Tilly et al. 2018 (The Lancet Oncology, 20(7), 998-1010.; of record). Although the claims at issue are not identical, they are not patentably distinct from each other because:
The claims of ‘787 are summarized above.
Regarding instant Claims 12-13, the claims of ‘787 are not drawn to the outcome measure of a 55% reduction in risk of disease progression, relapse or death.
Regarding instant Claims 99-100, the claims of ‘787 are not drawn to a method of treating DLBCL further comprising a prophylaxis for tumor lysis syndrome.
These deficiencies are obvious over Tilly and/or inherent to the method as claimed in ‘787.
Tilly teaches a method of treating diffuse large B-cell lymphoma (DLBCL) comprising six to eight 21-day cycles comprising IV administration of 750 mg/m2 cyclophosphamide, 50 mg/m2 doxorubicin, 375 mg/m2 rituximab, and 1.8 mg/kg polatuzumab vedotin on day 1 of each cycle and oral administration of 100 mg prednisone daily for days 1-5 of each cycle (Pg. 1000, § Procedures; Supplemental Protocol §4.3.2 Dosage, Administration, and Compliance).
Regarding instant Claims 99-100, Tilly teaches that prophylaxis for tumor lysis syndrome includes a hydration regimen of 3 L/day starting 1 or 2 days before the first study dose and 300 mg/day allopurinol starting 48-72 hours before Cycle 1 (Supplemental Protocol §5.1.7.1).
Regarding instant Claim 128, Tilly teaches that disease progression, including death from any cause, is assessed using the 2014 Lugano Response Criteria (Supplemental Protocol §3.4.3; Appendix 3).
Regarding the particular outcome measures of instant Claims 12-13, the method of ‘787 comprises the same therapeutics administered at the same doses according to the same schedule to the patients having the same disease as instantly claimed. Accordingly, any outcomes achieved in practicing the Pola-R-CHP method of ‘787 are inherent to said method necessarily flow from its practice.
Response to Arguments
Applicant's arguments filed 11/04/2025 have been fully considered but they are not persuasive because:
Applicant requests that the nonstatutory double patenting rejection in abeyance (Remarks Pg. 32). MPEP § 804(I)(B)(1) sates only compliance with objections or requirements as to form not necessary for further consideration of the claims may be held in abeyance until allowable subject matter is indicated. The nonstatutory double patenting rejection is above.
Conclusion
No claim is allowed.
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/BRYAN WILLIAM HECK/Examiner, Art Unit 1643
/JULIE WU/Supervisory Patent Examiner, Art Unit 1643