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 .
DETAILED ACTION
Claims 1-14 and 16-19 are cancelled.
Claim 15 is amended.
Claims 20-33 are new.
Claims 15 and 20-33 are examined herein.
Priority
The instant application claims benefit of priority to U.S. Provisional Application No. 63008359, filed on 10 April 2020 and PCT/US2021/026907, filed on 12 April 2021.
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, U.S. Provisional Application No. 63008359, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. The subject matter of comparing to a reference sample of a healthy individual in claims 15 and 20-33 is not enabled in the provisional application and are not entitled to the benefit of the prior application. Therefore, claims 15 and 20-33 receives the effective filing date of 12 April 2021.
Information Disclosure Statement
The information disclosure statement (IDS), submitted on 23 January 2024, is acknowledged and considered. The submissions are in compliance with the provisions of 37 CFR 1.97.
Response to Arguments
The amendment filed on 31 January 2026 has been entered.
In view of applicant cancellation of claims 3 and 4, the 112(a)-written description rejection of record is withdrawn.
In view of applicant cancellation of claims 3, 7, 8, 10-12, 14, and 19, the 112(b) rejections of record are withdrawn.
In view of applicant cancellation of claims 4, 10, 11, 12, 14, and 19, the 112(d) rejections of record are withdrawn.
In view of applicant cancellation of claims 1-8, the 102(a)(1) rejection of record is withdrawn.
In view of applicant cancellation of claim 14, the 103 rejection of record over McMorris in view of White and Verhaak is withdrawn.
In view of applicant cancellation of claim 19, the 103 rejection of record over McMorris in view of White and Mischel is withdrawn.
With respect to the sequence listing objection, it is noted that Applicant has submitted a corrected sequence listing however, the CRF was rejected as the Applicant submitted ST.26 format when ST.25 is required. Therefore the rejection is maintained.
With respect to the 103 rejections over McMorris, White and Regev, Applicant amendment has been considered but is not found persuasive for at least the following reasons. The Applicant argues that White (WO2018237327) discloses a method of measuring MGMT promotor methylation and not MGMT expression. Measuring the amount of methylated MGMT is a way to measure the expression of MGMT. High methylation is low expression of MGMT, low methylation is high expression of MGMT. Furthermore, the instant specification uses promoter methylation measurements (Table 1). Therefore the rejections are maintained and modified in light of the claim amendments.
In addition, new 112 (a), 112(b), and 103 rejections are necessitated by amendment (see below).
All rejections and objections not found below have been withdrawn.
MAINTAINED OBJECTIONS
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency - This application contains sequence disclosures in accordance with the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.821(a)(1) and (a)(2). However, this application fails to comply with the requirements of 37 CFR 1.821 - 1.825.
The sequence disclosures are located on pages 15-18 of the specification. The CRF file for Sequence ID No. 10 is not compliant.
Required response – Applicant must provide:
A "Sequence Listing" part of the disclosure, as described above in item 1); as well as
An amendment specifically directing entry of the "Sequence Listing" part of the disclosure into the application in accordance with 1.825(b)(2);
A statement that the "Sequence Listing" includes no new matter in accordance with 1.825(b)(5); and
A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.825(b)(4).
If the "Sequence Listing" part of the disclosure is submitted according to item 1) a) or b) above, Applicant must also provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter;
If the "Sequence Listing" part of the disclosure is submitted according to item 1) b), c), or d) above, Applicant must also provide:
A replacement CRF in accordance with 1.825(b)(6); and
Statement according to item 2) a) or b) above.
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.
Claim(s) 15 and 20-22, and 26-28 is/are rejected under 35 U.S.C. 103 as being unpatentable over McMorris et al. (WO2007019308A2) in view of White (WO2018237327).
Regarding claim 15, McMorris discloses the method of treating cancer comprising administering a compound of Formula (I). McMorris explicitly states the treatment can be for cancerous tumors of the central nervous system (CNS) and brain (page 8, line 30). Additionally, McMorris discloses hydroxyureamethyl-acylfulvene as a compound of Formula (I) (claim 34; pictured below).
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McMorris does not teach the method of measuring expression of genetic information of the cancer to compare to a reference.
White discloses a method of measuring genetic expression in a subject having or suspected of having glioblastoma by obtaining a biological sample from the subject, determining if the subject has MGMT methylation and then administering 4-iodo-3-nitrobenzamide to the subject if the subject has a MGMT promoter methylation (claim 1).
In KSR International Vo. V. Teleflex Inc., 82 USPQ2d (U.S. 2007), the Supreme Court particularly emphasized “the need for caution in granting a patent based on a combination of elements found in the prior art,” (Id. At 1395) and discussed circumstances in which a patent might be determined to be obvious.
In this case at least prong A of KSR applies – combining known methods for the same purpose of treating brain cancer. As both references disclose the method of treating brain cancer it would be prima facie obvious to one of ordinary skill in the art to combine the method of measuring expressed genetic information to determine the disease state of the subject, as taught by White, then apply the method of treatment as taught by McMorris. As both McMorris and White disclose treating brain cancer one skilled in the art would be motivated to combine the teachings.
Thus, all of the elements of claims were known to one of ordinary skill in the art at the time the invention was made and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions and the combination would have yielded nothing more than predictable results to one of ordinary skill in the art at the time of invention. Therefore, the claimed invention, as a whole, would have been obvious to one of ordinary skill in that art at the time the invention was made.
Regarding claim 20, White discloses the method of treating glioblastoma multiforme (paragraph [0138]).
Regarding claim 21, McMorris discloses the method treating central nervous system cancers (page 8, line 30) which would include brain stem glioma, craniopharyngioma, medulloblastoma, and meningioma.
Regarding claim 22, White discloses the method of obtaining tissue samples by biopsy (paragraph [0067]). White additionally discloses the method of performing MRIs on the patient every 8 weeks to monitor tumor (paragraph [0147]).
Regarding claim 26, McMorris discloses the method of intravenous administration (page 6, line 6).
Regarding claim 27, McMorris discloses the suitable dose range to be 0.5 to 100 mg/kg (page 18, line 20) and discloses dosing three times a week (page 22, line 12). While this does not work out to be exactly every other day, the dosing is close and in the absence of criticality would be considered routine optimization. See MPEP 2144.05.II.A.
Regarding claim 28, McMorris discloses the dosing schedule of three times a week on a 21-day treatment cycle. Reduction of this dosing would be considered routine optimization in the absence of criticality. See MPEP 2144.05.II.A.
Claim(s) 15 and 20-22, 26-29, and 31-33 is/are rejected under 35 U.S.C. 103 as being unpatentable over McMorris et al. (cited above) in view of White (cited above) in further view of Regev et al. (WO2019070755A1).
The teachings of McMorris and White are disclosed above and incorporated by reference herein.
Regarding the combined teachings of McMorris and White do not teach measuring the expression of genetic information wherein the genetic information is LAMB1, UGDH, ANXA2, S100A1, and CTSB.
Regev discloses the method of detecting the expression of a gene in tumor cells. Regev discloses the detection of LAMB1, UGDH, ANXA2, S100A11, and CTSB.
It would be prima facie obvious to the skilled artisan to combine the teachings of McMorris and White with that of Regev and measure for the expression of additional genes known to assist in the prognosis and treatment of the cancer. The skilled artisan would be motivated to combine these teachings as Regev discloses the method for detection of gene signatures in the prognosis of brain cancer (paragraph [0307]), the same condition taught by McMorris and White.
Regarding claim 31, Regev discloses the detection of APP (claim 1).
Regarding claim 32, Regev discloses the method of measuring transcript expression (paragraph [374]).
Regarding claim 33, McMorris discloses the suitable dose range to be 0.5 to 100 mg/kg (page 18, line 20) and discloses dosing three times a week (page 22, line 12). While this does not work out to be exactly every other day, the dosing is close and in the absence of criticality would be considered routine optimization. See MPEP 2144.05.II.A.
NEW REJECTONS NECESSITATED BY AMENDMENT
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 25, 27, 30-31, and 33 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 25 recites “the method of claim 15, wherein MGMT is measured..”. This is unclear. It is the Examiners opinion the claim should read “…wherein the MGMT expression level is measured…” or “…wherein the level of MGMT expression is measured…”.
The term “about” in claim 27 and 33 is a relative term which renders the claim indefinite. The term “about” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Claim 30 recites the limitation "wherein the at least on biomarker is EGFR.” There is insufficient antecedent basis for this limitation in the claim as EGFR is not one of the recited biomarkers in claim 29.
Claim 31 recites the limitation "wherein the at least one biomarker is APP.” There is insufficient antecedent basis for this limitation in the claim as APP is not one of the recited biomarkers in claim 29.
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.
Claim(s) 15 and 20-22, and 26-33 is/are rejected under 35 U.S.C. 103 as being unpatentable over McMorris et al. (cited above) in view of White (cited above) and Regev et al. (cited above), and in further view of Mischel et al. (WO2006116016A2).
The teachings of McMorris, White, and Regev are disclosed above and incorporated by reference herein.
Regarding claim 30, the combined teachings of McMorris, White, and Regev do not teach comparing the expression of a biological marker to a reference wherein the marker is EGFR.
Mischel teaches the method of identifying treatment response to a glioblastoma comprising examining the tumor cell for the expression of EGFR deletion mutant variant III.
It would be prima facie obvious to one of ordinary skill in the art to combine the teachings of McMorris, White, and Regev with that of Mischel and measure the expression of the EGFR mutant commonly found in glioblastomas. As both McMorris and White teach the methods of treating brain cancer, the skilled artisan would expect a reasonable level of success as the combined methods share the utility of treating brain cancer.
Claim(s) 15 and 20-28 is/are rejected under 35 U.S.C. 103 as being unpatentable over McMorris et al. (cited above) in view of White (cited above) in further view of Butler et al. (Trends Cancer. 2020;6(5):380–391).
The teachings of McMorris and White are disclosed above and incorporated by reference herein.
Regarding claims 23 and 24, the combination of McMorris and White does not teach measuring MGMT expression by determining the amount of MGMT mRNA or MGMT protein in a tumor sample.
Butler teaches MGMT as a biomarker in glioblastoma and tabulates current methods for evaluating MGMT status in Table 1, including promoter methylation, mRNA expression, and protein expression.
In KSR International Vo. V. Teleflex Inc., 82 USPQ2d (U.S. 2007), the Supreme Court particularly emphasized “the need for caution in granting a patent based on a combination of elements found in the prior art,” (Id. At 1395) and discussed circumstances in which a patent might be determined to be obvious.
In this case at least prong D of KSR applies – combining a known technique to a known method. It would be prima facie obvious to one skilled in the art to substitute the multiple methods of detecting MGMT status, as taught by Butler, with the method of determining only MGMT promoter methylation, as taught by White. Butler guides the skilled artisan to expanding the method of determining MGMT expression by explaining methylation and expression are not always correlated as there could be an additional mechanism affecting MGMT expression. As the utility of the detection methods is the same for White and Butler, i.e. as a biomarker for glioblastoma, the skilled artisan would have a reasonable expectation of success in applying the methods of Butler to the method of McMorris and White.
Thus, all of the elements of claims were known to one of ordinary skill in the art at the time the invention was made and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions and the combination would have yielded nothing more than predictable results to one of ordinary skill in the art at the time of invention. Therefore, the claimed invention, as a whole, would have been obvious to one of ordinary skill in that art at the time the invention was made.
Regarding claim 25, Butler teaches cutoff values for determining MGMT status of methylation and expression varies and recites a range overlapping with the instant 20% of 10-50%. Therefore, in the absence of criticality, this would be routine optimization. See MPEP 2144.05.II.A.
Conclusion
Claims 15 and 20-33 are rejected.
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 Jerica K Wilson whose telephone number is (703)756-4690. The examiner can normally be reached Monday-Friday 9:00-5:00.
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, Clinton Brooks can be reached at (571)270-7682. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/J.K.W./Examiner, Art Unit 1621
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621