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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 November 18, 2025 has been entered.
DETAILED ACTION
The amendment filed November 28, 2025 in response to the Office Action of August 27, 2025 is acknowledged and has been entered.
Claim 29 has been amended.
Claims 29, 31-48, and 50 are pending.
Claims 32, 33 and 48 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected inventions or species, there being no allowable generic or linking claim.
Claims 29, 31, 34-47 and 50 are currently under consideration as drawn to the elected invention.
NEW GROUNDS OF REJECTION
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 29, 31, 34-41, 43-47 and 50 are rejected under 35 U.S.C. 103 as being unpatentable over Vitolo (Vitolo et al., Blood 128 (22):470, Publication Date: 2016-12-02, in IDS of 04/24/2023, of record), in view of Scott (Scott et al., Blood, Vol. 123, Number 8, 1214-1217, Publication Date: 02/20/2014, in IDS of 04/24/2023, a copy of Scott with Suppl. is attached in this Office Action), as evidenced by Gabellier (Gabellier et al., Therapeutic Advances in Hematology, 7(2):85-93, Publication Date: 2015-12-27, in IDS of 04/24/2023, of record) and NCT01287741 (retrieved from: https://clinicaltrials.gov/ct2/show/NCT01287741, version of May 5, 2015, in IDS of 04/24/2023, of record) and GAZYVA (GAZYVA Prescribing Information, Reference ID: 4937323, in IDS of 04/24/2023, of record).
It’s noted that GCB COO DLBCL and ABC COO DLBCL are the same as GCB DLBCL and ABC DLBCL, respectively, as evidenced by the paragraph [0004] of the instant publication US 2023/0348611 A1 (“In particular, Scott (2014 and 2015 loc. cit.) assigned the COO subtypes of DLBCL, germinal-center B-cell-like DLBCL (GCB DLBCL), activated B-cell-like DLBCL (ABC DLBCL) and unclassified DLBCL”).
Regarding claims 29, 31, and 45-47, Vitolo teaches that Obinutuzumab (GA101; GAZYVA/GAZYVARO; G) is a glycoengineered, type II anti-CD20 monoclonal antibody with greater direct cell death induction and antibody-dependent cellular cytotoxicity/phagocytosis activity than rituximab, See Background. As evidenced by the instant Sequence Listing and claim 40, Obinutuzumab has a heavy chain variable region of SEQ ID NO:1 and a light chain variable region of SEQ ID NO:2 of the instant application, See paragraph [0442]. Thus, Obinutuzumab reads on the humanized Type II anti-CD20 antibody of the instant claim 29.
Vitolo teaches a clinical trial: patients were randomized 1:1 to receive 8 (21-day) cycles of Obinutuzumab (1000mg i.v. on Days 1, 8, and 15, Cycle 1 and Day 1, of Cycles 2-8) or rituximab (375mg/m2 i.v. on Day 1, Cycles 1-8) in combination with 6 or 8 cycles of CHOP (number of cycles preplanned in advance for all patients at each site). Preplanned radiotherapy was allowed for bulky or extranodal disease. The primary endpoint was investigator (INV)-assessed progression-free survival (PFS); for the target hazard ratio (HR) of 0.75, the 3-year PFS was expected to improve from 60% to 68%. Secondary endpoints included: PFS assessed by Independent Review Committee (IRC); overall survival (OS); complete response (CR) and overall response rate (ORR) with or without PET; and safety. See Methods.
Vitolo teaches that in a prespecified subgroup analysis of INV-assessed PFS, a stratified HR of 0.72 (95% CI, 0.50, 1.01) in favor of Obinutuzumab-CHOP over rituximab-CHOP was determined for pts with GCB DLBCL (3-year PFS, 79% vs. 70%), See Results.
Vitolo teaches as set forth above. However, Vitolo does not explicit teach wherein a tumor sample from the patient treated with Obinutuzumab/GA101 has a germinal center B-cell-like (GCB) cell-of-origin (COO) status identified by an overexpression of each of MME, SERPINA9, ASB13, MAML3, ITPKB, MYBL1, and S1PR2 in the tumor sample.
Scott teaches that GCB DLBCL and ABC DLBCL have distinct patterns of gene expression (§ Introduction).
Scott teaches gene expression profiling in tumor samples of 67 de novo DLBCL patients (Fig. 1, and § Study Design). Fig. 1A and Fig. S2 show all DLBCL patients with an overexpression of each of MME, SERPINA9, ASB13, MAML3, ITPKB, MYBL1, and S1PR2 in the tumor sample has a GCB status DLBCL based on the “Gold Standard”. In addition, none of the ABC DLBCL has an overexpression of each of MME, SERPINA9, ASB13, MAML3, ITPKB, MYBL1, and S1PR2 in the tumor sample.
Scott teaches the level of gene expression was mRNA expression (see Fig. 1 and Fig. S2 heat bar).
It would have been prima facie obvious to one of ordinarily skilled in the art at the time the invention was filed to treat GCB DLBCL patients with a therapy comprising administering a combination of Obinutuzumab and CHOP, as taught by Vitolo, and to further apply method taught by Scott to check the expression of MME, SERPINA9, ASB13, MAML3, ITPKB, MYBL1, and S1PR2 in the tumor sample of the patients to confirm the GCB DLBCL status for those have high/overexpression expression (e.g. mRNA expression level) for each of MME, SERPINA9, ASB13, MAML3, ITPKB, MYBL1, and S1PR2, because Scott teaches that DLBCL patients with an overexpression of each of MME, SERPINA9, ASB13, MAML3, ITPKB, MYBL1, and S1PR2 in the tumor sample have a GCB status DLBCL based on the “Gold Standard”. And none of the ABC DLBCL has an overexpression of each of MME, SERPINA9, ASB13, MAML3, ITPKB, MYBL1, and S1PR2 in the tumor sample. One of ordinary skill in the art would have been motivated to find the optimal patient population for cancers like GCB DLBCL by combining the method of Vitolo and method of Scott. Based on the teaching of the references, one of ordinary skilled in the art would have had a reasonable expectation that DLBCL patients with overexpression of MME, SERPINA9, ASB13, MAML3, ITPKB, MYBL1, and S1PR2 are most likely to be GCB DLBCL patients (a GCB COO status). Given that the methods are documented in the references, one of skill in the art would have had a reasonable expectation of success of using the methods in combination.
Regarding, claims 34 and 35 the Obinutuzumab/GA101 antibody of Vitolo is the same antibody as instantly claimed and thus would have the same effects on clinical outcome as claimed in claims 34 and 35.
Regarding claims 36-40, as evidenced by Gabellier, “Obinutuzumab is the first humanized glycoengineered IgG1 anti-CD20 mAb to be tested in clinical trials. Obinutuzumab has been humanized by grafting the complementarity-determining region sequences from the murine antibody B-ly1 into human VH and VL acceptor frameworks. Obinutuzumab was expressed from Chinese hamster ovary (CHO) K1 cell lines engineered to constitutively overexpress the heavy and light chains of Obinutuzumab as well as recombinant wild-type β-1,4-N-acetyl-glucosaminyltransferase III and wild-type Golgi α-mannosidase II leading to accumulation of antibody glycoforms containing bisected, complex, nonfucosylated oligosaccharides attached to asparagine 297 in the Fc region”, See the bridging paragraph of pages 86 and 87. Furthermore, such modifications induce increased affinity of Obinutuzumab to both FcγRIIIa-158V and -158F compared with rituximab, translating into an increased induction of ADCC relative to rituximab in vitro, See page 87, col. 1 and para. 2.
Regarding claims 41 and 43, as evidenced by NCT01287741, cyclophosphamide, doxorubicin, vincristine and prednisolone are administered through iv every 21 days 6 or 8 cycles (CHOP therapy), See Assigned Interventions.
Regarding claims 44, as evidenced by GAZYVA, GAZYVA is a sterile, clear, colorless to slightly brown, preservative-free liquid concentrate for intravenous use. GAZYVA is supplied at a concentration of 25 mg/mL in 1,000 mg single-dose vials. The product is formulated in 20 mM L-histidine/L-histidine hydrochloride, 240 mM trehalose, 0.02% poloxamer 188. The pH is 6.0. See page 22, § DESCRIPTION.
Regarding claim 50, Scott teaches the level of gene expression was mRNA expression (see Fig. 1 and Fig. S2 heat bar), it would have prima facie been obvious to one of ordinarily skilled in the art at the time of filing the invention to use the method of Scott to check gene expression by measuring mRNA expression level, because the method has been tested and well-known in the art, as evidenced by Scott.
Claim 42 is rejected under 35 U.S.C. 103 as being unpatentable over Vitolo (Vitolo et al., Blood 128 (22):470, Publication Date: 2016-12-02, in IDS, of record), in view of Scott (Scott et al., Blood, Vol. 123, Number 8, 1214-1217, Publication Date: 02/20/2014, in IDS of 04/24/2023, a copy of Scott with Suppl. is attached in this Office Action), as evidenced by Gabellier (Gabellier et al., Therapeutic Advances in Hematology, 7(2):85-93, Publication Date: 2015-12-27, in IDS of 04/24/2023, of record) and NCT01287741 (retrieved from: https://clinicaltrials.gov/ct2/show/NCT01287741, version of May 5, 2015, in IDS of 04/24/2023, of record) and GAZYVA (GAZYVA Prescribing Information, Reference ID: 4937323, in IDS of 04/24/2023, of record), as applied to claims 29-31, 34-41, 43-47, and 54 above, and further in view of Miller (Miller et al., The New England Journal of Medicine, 339 (1): 21-26, Publication Date: 1998-07-02, in IDS of 04/24/2023), as evidenced by The Science Behind Radiation Therapy (American Cancer Society, Publication Date: 2014-10-27, in IDS of 04/24/2023) and DLBCL (retrieved from on March 3, 2022: https://lymphoma.org/aboutlymphoma/nhl/dlbcl/, in IDS of 04/24/2023, of record).
Vitolo and Scott teach as set forth above, including preplanned radiotherapy was allowed (see Method of Vitolo). However, Vitolo does not explicitly teach the method of claim 41 further comprising administering to the patient ionizing radiation enhancing the effects of the one or more cytotoxic agents or the one or more chemotherapeutic agents.
As evidenced by the Science Behind Radiation Therapy: “Radiation used for cancer treatment is called ionizing radiation because it forms ions (electrically charged particles) in the cells of the tissues it passes through. It creates ions by removing electrons from atoms and molecules. This can kill cells or change genes so the cells stop growing”, See pages 3-4, § Types of radiation used to treat cancer. Thus, administering a radiotherapy reads on “administering to the patient ionizing radiation”.
Miller teaches that patients with clinically localized, intermediate- or high-grade non-Hodgkin's lymphoma usually receive initial treatment with a doxorubicin-containing regimen such as cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). Pilot studies suggest that eight cycles of CHOP alone or three cycles of CHOP followed by involved-field radiotherapy are effective in such patients. See whole document, Abstract in particular.
Miller teaches comparisons of these two approaches in a prospective, randomized, multi-institutional study. The end points were progression-free survival, overall survival, and life-threatening or fatal toxic effects. Two hundred eligible patients were randomly assigned to receive CHOP plus radiotherapy, and 201 received CHOP alone. See whole document, Abstract in particular.
Miller teaches that patients treated with three cycles of CHOP plus radiotherapy had significantly better progression-free survival (P=0.03) and overall survival (P=0.02) than patients treated with CHOP alone. The five-year estimates of progression-free survival for patients receiving CHOP plus radiotherapy and for patients receiving CHOP alone were 77 percent and 64 percent, respectively. The five-year estimates of overall survival for patients receiving CHOP plus radiotherapy and for patients receiving CHOP alone were 82 percent and 72 percent, respectively. The adverse effects included one death in each treatment group. Life-threatening toxic effects of any type were seen in 61 of 200 patients treated with CHOP plus radiotherapy and in 80 of 201 patients treated with CHOP alone (P=0.06). The left ventricular function was decreased in seven patients who received CHOP alone, whereas no cardiac events were recorded in the group receiving CHOP plus radiotherapy (P=0.02). See whole document, Abstract in particular.
Miller teaches that three cycles of CHOP followed by involved-field radiotherapy are superior to eight cycles of CHOP alone for the treatment of localized intermediate- and high-grade non-Hodgkin's lymphoma. See whole document, Abstract in particular.
It is also noted that DLBCL is the most common type of non-Hodgkin lymphoma in the United States and worldwide, as evidenced by DLBCL, See paragraph 1.
It would have been prima facie obvious to one of ordinarily skilled in the art at the time the invention was filed to treat GCB DLBCL patients with a therapy comprising administering a combination of Obinutuzumab and CHOP, as taught by Vitolo and Scott, and further add a step of administering to the patient ionizing radiation (radiotherapy), as taught by Miller, because ionizing radiation can significantly enhance the CHOP therapy’s therapeutic efficacy. Based on the teaching of the references, one of ordinary skilled in the art would have had a reasonable expectation that adding radiotherapy would improve the therapeutic efficacy for treatment method of claim 29. One of skill in the art would have been motivated to find the optimal treatment for cancers like GCB DLBCL by combining the method of Vitolo/Scott and method of Miller. Given that the methods are documented in the references, one of skill in the art would have had a reasonable expectation of success of using the methods in combination.
Response to Arguments
For the 103 rejections on claims 29, 31, 34-41, 43-47 and 50, Applicant first argues:
The present invention is based, at least in part, on Applicants' surprising discovery that patients having such a biomarker signature have an improved clinical outcome when administered a treatment comprising obinutuzumab (e.g., G-CHOP) relative to those who are administered a treatment comprising rituximab (e.g., R-CHOP, which is the standard-of-care treatment for previously untreated DLBCL). This surprising discovery is nowhere taught or suggested by the cited references.
Applicant’s arguments have been fully considered but they are not persuasive. Applicant alleges that “patients having such a biomarker signature have an improved clinical outcome when administered a treatment comprising obinutuzumab (e.g., G-CHOP) relative to those who are administered a treatment comprising rituximab (e.g., R-CHOP, which is the standard-of-care treatment for previously untreated DLBCL)”, however, the data in the specification do not describe any patient population identified by an overexpression of each of MME, SERPINA9, ASB13, MAML3, ITPLB, MYBL1, and SIPR2 in the tumor sample. Instead, in the GOYA trial, the patient group, which shows an improved clinical outcome to G-CHOP treatment, was identified by an optimal Linear Predictor Score (LPS) cutoff (≤ 725) ([0440] of the instant publication US 2023/0348611 A1, Example 3.2). Similarly, Example 3.1 also classified patient subgroup by LPS cutoff ([0433] of the instant publication US 2023/0348611 A1). Paragraphs [0302]-[0304] and Table 8 of the instant publication US 2023/0348611 A1 teach that LPS is a weighted sum of the gene expression of the 20 genes in the LST assay. Thus, the specification does not show any “surprising” results with the patient population as claimed.
In addition, Vitolo teaches that in a prespecified subgroup analysis of INV-assessed PFS, a stratified HR of 0.72 (95% CI, 0.50, 1.01) in favor of Obinutuzumab-CHOP over rituximab-CHOP was determined for pts with GCB DLBCL (3-year PFS, 79% vs. 70%), See Results. Scott teaches that DLBCL patients with an overexpression of each of MME, SERPINA9, ASB13, MAML3, ITPKB, MYBL1, and S1PR2 in the tumor sample all have a GCB status DLBCL based on the “Gold Standard”. Based on the teaching of the references, one of ordinary skilled in the art would have had a reasonable expectation that DLBCL patients with overexpression of MME, SERPINA9, ASB13, MAML3, ITPKB, MYBL1, and S1PR2 are most likely to be GCB DLBCL patients (a GCB COO status) and will have a favorable response to Obinutuzumab-CHOP.
Thus, the rejection is proper in view of new combined references as set forth above.
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 29, 31, 34-47 and 50 are alternatively rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-26 of U.S. Patent No. 11,597,772 B2 (hereinafter, Pat. 772, corresponding to Appl. No. US 16/784,021) and in view of Vitolo (Vitolo et al., Blood 128 (22):470, Publication Date: 2016-12-02, in IDS) and Scott (Scott et al., Blood, Vol. 123, Number 8, 1214-1217, Publication Date: 02/20/2014, in IDS of 04/24/2023, a copy of Scott with Suppl. is attached in this Office Action), as evidenced by Gabellier (Gabellier et al., Therapeutic Advances in Hematology, 7(2):85-93, Publication Date: 2015-12-27, in IDS of 04/24/2023, of record) and NCT01287741 (retrieved from: https://clinicaltrials.gov/ct2/show/NCT01287741, version of May 5, 2015, in IDS of 04/24/2023, of record) and GAZYVA (GAZYVA Prescribing Information, Reference ID: 4937323, in IDS of 04/24/2023, of record).
Regarding claims 29 and 31, the claims of Pat. 772 teach:
1. A method of treating a patient having a diffuse large B-cell lymphoma (DLBCL), the method comprising administering to the patient a therapeutically effective amount of a humanized Type II anti-CD20 antibody, wherein a tumor sample from the patient has a germinal center B-cell-like (GCB) cell-of-origin (COO) status;
wherein the humanized Type II anti-CD20 antibody comprises a heavy chain variable region comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 1 and a light chain variable region comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 2; and
wherein the GCB COO status is a strong GCB COO status identified by a linear predictor score linear predictor score (LPS) for the tumor sample that is less than 1141, and wherein the LPS is a weighted sum of the expression levels of the genes …, MME, SERPINA9, ASB13, MAML3, ITPKB, MYBL1, S1PR2, …, and is calculated according the formula:
LPS(X)=Σj a j X j, wherein Xj is the gene expression for gene j and aj is the coefficient for gene j.
2. The method of claim 1, wherein the humanized Type II anti-CD20 antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 1 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 2.
3. The method of claim 1, wherein the tumor sample from the patient further has (a) one or more mutations in one or more of CREBBP, EP300, MEF2B, MYC, EZH2, and TNFRSF14 and (b) one or both of (i) one or more genetic mutations in CD58 and (ii) an expression level of CD58 that is less than 5.3 log2(nRPKM).
4. The method of claim 1, wherein the tumor sample from the patient further has one or both of (i) a translocation of BCL2 and (ii) a high expression level of BCL2 as compared to a control.
Thus the claims of Pat. 772 teach a method of treating a diffuse large B-cell lymphoma (DLBCL) with a strong GCB COO status with the same antibody (e.g. Obinutuzumab, see claim ) as the instant claims. However, the claims of Pat. 772 do not explicitly teach strong (GCB) cell-of-origin (COO) status identified by an overexpression of only each of MME, SERPINA9, ASB13, MAML3, ITPKB, MYBL1, and S1PR2 in the tumor sample.
Vitolo and Scott teach as set forth above in the 103 rejection above.
It would have been prima facie obvious to one of ordinarily skilled in the art at the time the invention was filed to treat GCB DLBCL patients with a therapy comprising administering a combination of Obinutuzumab and CHOP, as taught by the claims of Pat. 772 and Vitolo, because GCB DLBCL show good response to the treatment; and to further apply method taught by Scott to check the expression of MME, SERPINA9, ASB13, MAML3, ITPKB, MYBL1, and S1PR2 in the tumor sample of the patients to confirm the GCB DLBCL status for those have high expression (e.g. mRNA expression level) of MME, SERPINA9, ASB13, MAML3, ITPKB, MYBL1, and S1PR2, because Scott teaches that all DLBCL patients with an overexpression of each of MME, SERPINA9, ASB13, MAML3, ITPKB, MYBL1, and S1PR2 in the tumor sample has a GCB status DLBCL based on the “Gold Standard”. And none of the ABC DLBCL has an overexpression of each of MME, SERPINA9, ASB13, MAML3, ITPKB, MYBL1, and S1PR2 in the tumor sample. One of skill in the art would have been motivated to find the optimal patient population for cancers like GCB DLBCL by combining the method of Vitolo and method of Scott. Based on the teaching of the references, one of ordinary skilled in the art would have had a reasonable expectation that DLBCL patients with overexpression of MME, SERPINA9, ASB13, MAML3, ITPKB, MYBL1, and S1PR2 are most likely to be GCB DLBCL patients (a GCB COO status). Given that the methods are documented in the references, one of skill in the art would have had a reasonable expectation of success of using the methods in combination particularly given that Vitolo demonstrated PFS.
Regarding claim 34, claim 5 of Pat. 772 teaches the method of claim 1, wherein the patient reaches an improved clinical outcome as compared to a patient treated with rituximab.
Regarding claim 35, claim 6 of Pat. 772 teaches the method of claim 5, wherein the clinical outcome is progression-free survival (PFS), overall survival (OS), or event-free survival (EFS).
Regarding claim 36, claim 7 of Pat. 772 teaches the method of claim 1, wherein the humanized Type II anti-CD20 antibody comprises a glycoengineered Fc region.
Regarding claim 37, claim 8 of Pat. 772 teaches the method of claim 7, wherein the humanized Type II anti-CD20 antibody has an increase in the fraction of non-fucosylated oligosaccharides attached to the glycoengineered Fc region relative to an anti-CD20 antibody that comprises a non-glycoengineered Fc region.
Regarding claim 38, claim 9 of Pat. 772 teaches the method of claim 8, wherein the non-fucosylated oligosaccharides are bisected non-fucosylated oligosaccharides.
Regarding claim 39, claim 10 of Pat. 772 teaches the method of claim 1, wherein the humanized Type II anti-CD20 antibody has an increased affinity for human FcγRIII receptors relative to an anti-CD20 antibody that comprises a non-glycoengineered Fc region or rituximab. Claim 11 of Pat. 772 teaches the method of claim 1, wherein the humanized Type II anti-CD20 antibody is capable of causing increased antibody-dependent cellular cytotoxicity (ADCC) relative to a non-glycoengineered antibody.
Regarding claim 40, claim 13 of Pat. 772 teaches the method of claim 1, wherein the antibody is obinutuzumab.
Regarding claim 41, claim 14 of Pat. 772 teaches the method of claim 1, further comprising administering to the patient one or more additional cytotoxic agents or chemotherapeutic agents.
Regarding claim 42, claim 15 of Pat. 772 teaches the method of claim 14, further comprising administering to the patient ionizing radiation enhancing the effects of the one or more cytotoxic agents or the one or more chemotherapeutic agents.
Regarding claim 43, claim 16 of Pat. 772 teaches the method of claim 14, comprising administering to the patient the chemotherapeutic agents (i) cyclophosphamide; (ii) doxorubicin; (iii) vincristine; and (iv) prednisone or prednisolone.
Regarding claim 44, claim 17 of Pat. 772 teaches the method of claim 1, wherein the humanized Type II anti-CD20 antibody is administered to the patient in a pharmaceutical composition comprising a pharmaceutically acceptable carrier.
Regarding claim 45, claim 18 of Pat. 772 teaches the method of claim 1, wherein the humanized Type II anti-CD20 antibody is administered intravenously at a dose of 1000 mg every three weeks.
Regarding claim 46, claim 19 of Pat. 772 teaches the method of claim 18, wherein the humanized Type II anti-CD20 antibody is administered on days 1, 8, and 15 of a first 21-day treatment cycle and on day 1 of one or more additional 21-day treatment cycles.
Regarding claim 47, claim 20 of Pat. 772 teaches the method of claim 19, wherein 8 cycles of treatment are administered.
Regarding claim 50, claim 22 of Pat. 772 teaches method of claim 1, wherein the expression levels of the genes are mRNA expression levels.
Response to Arguments
For the Double Patenting rejections on claims 29, 31, 34-47 and 50, Applicant argues:
This rejection is based, at least in part, on the premise that the present claims would have been obvious in view of the cited references Vitolo and Staudt for the reasons set forth in the § 103 rejection. Office Action, pages 20-21. For at least the reasons discussed above, the present claims are nonobvious over the cited references.
Applicant is reiterating the arguments set forth above. As set forth above, Vitolo in combination with Scott (the new reference) teach the patient population identification step as instantly claimed. Thus, the claims of Pat.772, Vitolo and Scott together teach the claimed invention.
Conclusion
No claims are allowed.
All rejections set forth in the previous Office Action of August 27, 2025 are hereby withdrawn in view of the claim amendments and Applicant’s arguments.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHENG LU whose telephone number is (571)272-0334. The examiner can normally be reached Monday-Friday 8-5.
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/CHENG LU/ Examiner, Art Unit 1642