DETAILED CORRESPONDENCE
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 .
This action is in response to the papers filed November 26, 2025. Currently, claims 2-12, 14-15 are pending.
Election/Restrictions
Applicant's election without traverse of TP53 promoter in Claim 2, in the paper filed November 26, 2025 is acknowledged.
Upon search and consideration, the election requirement of October 1, 2025 has been withdrawn.
Priority
PNG
media_image1.png
70
556
media_image1.png
Greyscale
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 2-12, 14-15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 12,054,781 in view of Pan et al. (Clinical Chemistry, Vol. 61, No. 3, pages 514-522, January 20, 2015). Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are species within the scope of the generic claims of U.S. Patent No. 12,054,781.
Claim 1 of U.S. Patent No. 12,054,781 recites
A method comprising: a) receiving a Cerebral Spinal Fluid (CSF) sample from a human with a primary brain tumor, wherein said primary brain tumor is a glioma, a medulloblastoma, or an ependymoma and has been determined by imaging to abut a CSF reservoir, wherein the CSF reservoir is a ventricular reservoir or a basal cistern; b) assaying tumor-specific DNA shed from said primary brain tumor in said CSF sample and determining the presence of one or more point mutations in said tumor-specific DNA; and c) assaying nucleic acids from a normal tissue from the human and determining absence of the one or more point mutations determined to be present in said tumor-specific DNA.
The claims of ‘781 do not teach the point mutation is in p53.
However, Pan teaches brain tumor mutations include mutations in p53. Therefore, it would have been prima facie obvious to have analyzed known brain tumor mutations in the method of ‘781. The ordinary artisan would have been motivated to have selected mutations known to be associated with brain tumors to assay brain tumors.
Citation of Relevant Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Pan et al. (Clinical Chemistry, Vol. 61, No. 3, pages 514-522, January 20, 2015). Pan teaches a method of obtaining CSF samples from humans with primary brain tumors and assaying nucleic acids in the CSF. Specifically, Pan teaches detecting DNA within CSF to characterize tumor specific mutations (abstract). Pan teaches using digital PCR and sequencing to quantify tumor mutations in the cfDNA of CSF from 7 patients with solid brain tumors. Pan teaches CSF, blood and brain tumor tissue were collected at the time of surgical resection (page 515, col. 1). Patient S2 had atypical meningioma and tumor DNA was detected. Atypical meningiomas form along the dura mater, the outermost layer of tissue that covers and protects the brain and spinal cord, and thus abut a CSF reservoir. The CSF was collected at the time of a clinically indicated lumbar puncture (page 515, col. 1). Pan also performs exome sequencing and ddPCR and targeted amplicon sequencing for tumor and normal DNA (page 516, col. 1). Pan further teaches considerable number of tumor cells grow along the dura and meninges of patients with leptomeningeal disease, cellular DNA in CSF constitutes an important source of tumor DNA.
McAllister (Primary Central Nervous System Lymphoma: A Review, pages 210-215, 2002). McAllister teaches primary central nervous system lymphoma (PCNSL) is an aggressive non-Hodgkin’s lymphoma associated with poor prognosis without treatment (abstract). McAllister teaches assaying patients for CSF cytology or ocular involvement to make a diagnosis. McAllister teaches the majority (98%) of lesions abuts a CSF space. McAllister teaches nonspecific CSF abnormalities may be screened (page 211, col. 2) and combined with flow cytometry and morphologic examination to increase diagnostic value (page 211, col. 2). McAllister teaches relapse is problematic.
Bruno et al. (Abstract 3896: Recurrent TERT promoter mutations in primary central nervous system lymphoma; Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA) Forty-one PCNSL tumor samples of newly diagnosed PCNSL were sequenced for C228T and C250T TERT somatic mutations. TERT promoter mutations status was correlated with clinical outcome.
Eichler et al. (Neurosurg Focus, Vol. 5, E16, 2006). Eichler teaches primary central nervous system lymphoma: presentation, diagnosis and staging. Eichler teaches Primary Central Nervous system lymphoma (PCNSL) affects the brain and the spinal cord, for example (abstract). Eichler teaches imaging and cerebrospinal fluid (CSF) analysis are performed for PCNSL. Eichler teaches patients with evidence of spinal cord dysfunction should have contrast-enhanced MR imaging of the entire spine (abstract). Eichler teaches the location of PCNSL lesions, like all masses in the CNS, determines the clinical presentation. Specifically, the symptoms and signs of intramedullary spinal cord lymphoma resemble those of other intramedullary spinal tumors and depend on the lesion’s location within the spinal cord (page 2, col. 1). Intramedullary tumors arise within the spinal cord itself and thus abut a CSF reservoir. Table 2 illustrates diagnostic evaluation of patients includes contrast enhanced spinal MRI and PCR for immunoglobulin heavy-chain clonal rearrangements (page 5, col. 1). Eichler teaches PCR is gaining broader use (page 4, col. 2). The use of PCR studies for CSF analysis has been used to detect clonal rearrangements. Re-arrangements are mutations (page 5, col. 1).
None of the references teach the primary brain tumor is glioma, medulloblastoma or ependymoma or determining by imaging the tumor abuts a ventricular reservoir or basal cistern.
Conclusion
No claims allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEANINE ANNE GOLDBERG whose telephone number is (571)272-0743. The examiner can normally be reached on Monday-Friday 6am-3:30pm.
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, Wu-Cheng (Winston) Shen can be reached on (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 an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JEANINE A GOLDBERG/Primary Examiner, Art Unit 1634 February 12, 2026