DETAILED ACTION
The amendment filed on 04/07/2026 has been entered.
Claims 1-2, 9 and 12 were amended in the claim set filed on 04/07/2026.
Applicant's election with traverse of Group I, claims, 1-6 and 9, drawn to a method for diffuse large B-cell lymphoma prognosis and treatment in a patient in need thereof, in the reply filed on 12/08/2025 is acknowledged. The
Applicant is reminded that upon the cancelation of claims to a non-elected invention, the inventorship must be corrected in compliance with 37 CFR 1.48(a) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. A request to correct inventorship under 37 CFR 1.48(a) must be accompanied by an application data sheet in accordance with 37 CFR 1.76 that identifies each inventor by his or her legal name and by the processing fee required under 37 CFR 1.17(i).
Claims 12-19 and 30 are withdrawn drawn to a nonelected Group II, III or V. Applicant timely traversed the restriction (election) requirement for claims 12-15 in the reply filed on 12/08/2025.
Claims 4-5 and 20-23 were canceled in the claim set filed on 04/07/2026.
Claims 1-3, 6 and 9 in the claim set filed on 04/07/2026 are currently under examination.
Response to the Arguments
Applicant’s arguments regarding traversal of the restriction requirement have been considered but are not persuasive. The restriction requirement between Groups I and II are maintained after further amendment as the language of the claims remains open-ended. Claims 12-15 remain restricted as Group II.
Claim objections have been withdrawn in light of applicants claim amendments.
Applicant’s arguments regarding previous rejection(s) of claim(s) 1 under 35 U.S.C. 112 have been fully considered and are persuasive. The 35 U.S.C. 112 rejections documented in the previously mailed non-final have been withdrawn in light of applicants claim amendments and arguments on Pg. 7.
Applicant’s arguments regarding previous rejection(s) of claim(s) 1-3, 6 and 9 under 35 U.S.C. 101 have been fully considered and are persuasive. As necessitated by amendment, the 35 U.S.C. 101 rejections documented in the previously mailed non-final have been withdrawn in light of applicants claim amendments and arguments on Pg. 7-9.
Applicant’s arguments regarding previous rejection(s) of claim(s) 1-3, 6 and 9 under 35 U.S.C. 103 have been fully considered and are persuasive. As necessitated by amendment, the 35 U.S.C. 103 rejections of claim(s) 1-3, 6 and 9 documented in the previously mailed non-final have been withdrawn in light of applicants claim amendments and arguments on Pg. 7-9. However, upon further consideration and search, new grounds of rejection are made as documented below in the 35 U.S.C. 103 rejection in this office action on Pg. 17-36.
The revised rejections for claims 1-3, 6 and 9 are documented below in this Final Office Action are necessitated by claim amendments filed on 04/07/2026.
Priority
The present application is the U.S. National Stage of International Patent Application No. PCT/US2021/056774, filed October 27,2021, which claims the priority benefit of U.S. Provisional Patent Application Serial No. 63/105,970, filed October 27, 2020.
Claim Rejections - 35 USC § 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 1-3, 6 and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Staudt et al. (“Staudt”; Patent App. Pub. No. US 20110152115 A1, June 23, 2011) in view of Knudsen et al. (“Knudsen”; Patent App. Pub. No. US 20180087113 A1, March 29, 2018).
Staudt discloses “The present invention discloses methods for identifying, diagnosing, and predicting survival in a lymphoma or lymphoproliferative disorder on the basis of gene expression patterns. The invention discloses a novel microarray, the Lymph Dx microarray, for obtaining gene expression data from a lymphoma sample. The invention also discloses a variety of methods for utilizing lymphoma gene expression data to determine the identity of a particular lymphoma and to predict survival in a subject diagnosed with a particular lymphoma. This information is useful in developing the appropriate therapeutic approach for use with a particular subject.”(Abstract)
Regarding claims 1-2, Staudt teaches a method comprising “a biopsy sample is obtained from the subject and gene expression data is obtained from the biopsy sample” (Para. 13). Staudt teaches a method comprising LMO2, LY75, SLAMF1, TNFRSF9, PDK1, GNG8, ECT2 AND NEK3 (Table 2). Staudt also teaches a method comprising “gene expression data obtained using Affymetrix U133A and U133B microarrays” (Para. 77). Staudt teaches a method comprising “A step-up procedure was applied to determine the optimal number of gene signatures to use in the survival predictor model. First, the gene expression signature that was most significantly associated with survival was included in the model. Next, the gene expression signature with the second highest association with survival was added to the model to form a two-component model” (Para. 168). Staudt teaches a method comprising “23 PMBL signature genes” (Para. 40). Furthermore, Staudt teaches a method comprising “Hierarchical clustering is performed to group these genes into gene expression signatures, and the expression of all genes within each signature are averaged to obtain a gene expression signature value for each signature” (Para. 9; Para. 55). “Affymetrix U133A and U133B” read on a microarray used to determine the expression levels of ALDOC, ASIP, ATP8A1, CD1E, DUSP16, FAF1, GAREM, GNG8, LMO2, LPPR4, LY75, MAEL, PADI2, PDK1, PPP1R7, SCN1A, SLAMF1, SSTR2, TNFRSF9, USH2A, VEZF1, WDR91, ADRA2B, ECT2, ELOVL6, IGSF9, NEK3, PDK4, PES1, PUSL1, TADA2A, and ZMYND19. U133A reads on majority of the first gene expression profile except DUSP16, GNG8 and MAEL, which can be found on U133B. (see confirmed list provided by Ensemble-BioMart search). U133A reads on majority of the second gene expression profile except IGFS9, PUSL1 and ZMND19, which can be found on U133B. (see confirmed list provided by Ensemble-BioMart search). “23 PMBL signature genes” read on 23 genes to determine first expression profile. Thus, Staudt suggests a method of processing a biological sample from a diffuse large B-cell lymphoma (DLBCL) patient, said method comprising: obtaining a biological sample from the DLBCL patient; and determining a first gene expression profile in said biological sample by assaying said sample with a gene panel comprising a combination of at least ALDOC, ASIP, ATP8A1, CD1E, DUSP16, FAF1, GAREM, GNG8, LMO2, LPPR4, LY75, MAEL, PADI2, PDK1, PPP1R7, SCN1A, SLAMF1, SSTR2, TNFRSF9, USH2A, VEZF1, and WDR91; and further comprising: determining a second gene expression profile in said biological sample for combination of at least a second set of genes ADRA2B, ECT2, ELOVL6, IGSF9, NEK3, PDK4, PES1, PUSL1, TADA2A, and ZMYND19.
Staudt suggests a method comprising determining a first gene expression profile and second gene expression using Affymetrix U133A and U133B microarrays from the sample of a DLBCL patient. However, Staudt does not explicitly teach the limitations of “FAM223 Member A or B” or “a panel”.
Knudsen discloses “The present invention features methods, devices, and kits for detecting gene expression in a patient having cancer or determining responsive of a patient having cancer to a treatment, such as APO010. The invention further includes methods of treating a patient having cancer by administering, e.g., APO010.”(Abstract)
Regarding claims 1-2, Knudsen teaches a method comprising “quantified using, e.g., HG-U133A or HG-U133_Plus2 GeneChip from Affymetrix Inc. and compatible apparatus e.g. GCS3000Dx from Affymetrix, using the manufacturer's instructions. The resulting biomarker expression measurements may be further analyzed as described herein.” (Para. 60). Knudsen teaches a method comprising “the patient may have … diffuse large B-cell lymphoma (DLBCL)” (Para. 140). “HG-U133_Plus2” reads on the full list of genes listed in claim 1 and claim 2 (see confirmed list provided by Ensemble-BioMart search). Thus, Staudt and Knudsen further suggest a method comprising determining a first gene expression profile in said biological sample by assaying said sample with a gene panel comprising a combination of at least ALDOC, ASIP, ATP8A1, CD1E, DUSP16, FAF1, FAM223 Member A or B, GAREM, GNG8, LMO2, LPPR4, LY75, MAEL, PADI2, PDK1, PPP1R7, SCN1A, SLAMF1, SSTR2, TNFRSF9, USH2A, VEZF1, and WDR91; and further comprising: determining a second gene expression profile in said biological sample for combination of at least a second set of genes ADRA2B, ECT2, ELOVL6, IGSF9, NEK3, PDK4, PES1, PUSL1, TADA2A, and ZMYND19.
Staudt and Knudsen are both considered to be analogous to the claimed invention because they are in the same field of detecting gene expression in a patient having cancer. Therefore, it would have been obvious to someone of ordinary skill in the art before the effective filing date of the claimed invention to have modified the methods of method of processing a biological sample from a diffuse large B-cell lymphoma (DLBCL) patient using U133A and U133B as taught by Staudt by the HG-U133 Plus2 array the method of using a panel to determine the first and second gene expression profile according to the limitations of 1 and 2 as taught by Knudsen and provide a method for processing a biological sample from a diffuse large B-cell lymphoma (DLBCL) patient. One of ordinary skill in the art would be motivated to substitute the use of two arrays, HG-U133A and HG-U133B for one array, HG-U133 Plus2. These claim elements were known in the art and one of skill in the art could have simply substituted these known elements for another, and the substitution would have yielded the predictable outcome according to the limitations of claims 1 and 2. Doing so would allow for cancer diagnosis and prognosis valuation in DLBC patients.
Furthermore, claim 3, 6 and 9 depend on claim 1.
Regarding claim 3, Staudt teaches a method wherein “a biopsy sample is obtained from the subject… belonging to a lymph node” (Para. 15). Thus, Staudt teaches a method wherein said sample is lymph node tissue.
Regarding claim 6, Staudt teaches a method wherein “the gene expression data used in this method is obtained using a microarray.” (Para. 13). Thus, Staudt teaches a method wherein said first gene expression profile is determined by a system configured to assay a plurality of molecular targets in the biological sample to detect gene expression levels for said first set of genes, wherein said system is selected from the group consisting of microarray, PCR, immunoassay, quantitative PCR, and next- generation sequencing.
Regarding claim 9, Staudt teaches a method comprising “…As survival predictor scores increase (i.e., prognosis gets worse), subjects may receive more intensive treatments. Those subjects with the highest survival predictor scores (i.e., very poor prognosis) may receive experimental treatments or treatments with novel agents. Accurate survival prediction using the methods disclosed herein provides an improved tool for selecting treatment options and for predicting the likely clinical outcome of those options” (Para. 94). Thus, Staudt teaches a method further comprising administering a therapeutic treatment to said patient.
Regarding claim 9, Staudt teaches a method wherein “All patients from whom the samples were derived had been treated with anthracycline-containing multiagent chemotherapy protocols, with some patients additionally receiving radiation therapy. The training set was profiled for gene expression” (Para. 206). Thus, Staudt teaches a method further comprising repeating the determination of the first gene expression profile after administering said treatment to yield an updated first gene expression profile, and comparing the first gene expression profile to the updated first gene expression profile to determine efficacy of said treatment.
Response to Arguments
Applicant's arguments filed 04/07/2026 (Pg. 7-9) with respect to claims 1-3, 6 and 9 have been fully considered but they do not apply to the new grounds of rejection. To clarify some instances argued in the response filed 04/07/2026 see responses to each argument made by Applicant below:
Applicants’ argument: “Among the 23 specific genes in the first gene panel recited in claim 1, these 17 appear to be missing altogether from Staudt: ALDOC, ASIP, ATP8Al, CDlE, DUSP16, FAFl, FAM223AIFAM223B, GAREM, LPPR4, MAEL, PADI2, PPP1R7, SCNlA, SSTR2, USH2A, VEZFl, and WDR91. Stated another way, Staudt only even discloses 5 of Applicant's genes. And Applicant could not find any discussion in Staudt calling out these particular 5 or otherwise suggesting they be grouped together in a particular panel.”
Response: Applicant’s arguments have been fully considered and found unpersuasive because the expression of 22 of the 23 genes could be determined by HG-U133A and HG-U133B. Furthermore, expression of all 23 genes can be determined by using HG-U133 Plus2.
Conclusion of Response to Arguments
In view of the amendments, new grounds of rejections and above responses to arguments, no claims are in condition for allowance.
Conclusion
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 KENDRA R VANN-OJUEKAIYE whose telephone number is (571)270-7529. The examiner can normally be reached M-F 9:00 AM- 5:00 PM.
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, Winston Shen can be reached at (571)272-3157. 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.
/KENDRA R VANN-OJUEKAIYE/Examiner, Art Unit 1682
/WU CHENG W SHEN/Supervisory Patent Examiner, Art Unit 1682
Prosecution Insights