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 .
Claim Status
Currently, claims 1, 6, 10-19, 40-43 are pending in the instant application. Claim 2-5, 7-9, 20-39 have been canceled. Claims 6, 10-16 and 18 are withdrawn and claims 40-43 are newly added. All the amendments and arguments have been thoroughly reviewed but were found insufficient to place the instantly examined claims in condition for allowance. The following rejections are either newly presented, as necessitated by amendment, or are reiterated from the previous office action. Any rejections not reiterated in this action have been withdrawn as necessitated by applicant' s amendments to the claims. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action. This action is FINAL.
Claims 1, 17, 19, 40-43 are under examination. The claims are under examination with respect to the elected biomarker, CD45.
Withdrawn Rejections
The rejection of claims 1-3, 7-9, 17, 19-20 under 35 USC 101 is withdrawn in view of the amendment to the claims.
The rejection of claims 1, 7-9, 17, and 20 under 35 USC 102(a)(1) as being anticipated by Halbert is withdrawn in view of the amendment to the claims.
The rejection of claims 1-4, 8, and 19 under 35 U.S.C. 102(a)(1) as being anticipated by
Allen (WO2018/132287 A1) is withdrawn in view of the amendment to the claims.
New Grounds of Rejection – Necessitated by Amendment to the Claims
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.
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 1, 17, 19, 40-43 are rejected under 35 U.S.C. 103 as being unpatentable over Nuciforo (2018, cited on IDS) in view of Keegan (J Clin Oncol 35, 583 (2017)).
Nuciforo teaches on-treatment TILs but not baseline TILs are associated with response following anti-HER2 therapy. Nuciforo teaches a combined score of TILs and tumor cellularity measured at D15 provides predictive information upon completion of neoadjuvant anti-HER2 based therapy (see conclusions, pg. 1). Nuciforo teaches patients with HER2 positive breast cancer were treated with neoadjuvant lapatinib and trastuzumab for 18 weeks (administering a HER targeted therapeutic to an individual having HER2+ breast cancer) (HER2 targeted therapeutic is trastuzumab, lapatinib) (claim 40). Nuciforo teaches FFPE tumor samples at D15 of treatment were collected (see PAMELA study design) (obtaining on treatment cancer biopsy) (formalin fixed paraffin embedded, claim 19). Nuciforo teaches histopathological analysis of TILs was done of tumor tissue. Percentage of TILs and tumor cellularity at D15 were measured in biopsies from patients. D15 samples of PAMELA were used in a bivariate logistic regression model for pCR using tumor cellularity and TILs as variables (see tumor cellularity and TILS combined model at D15) (identifying one or more regions of interest within on treatment cancer biopsy, entering the set of on treatment biomolecular expression into a trained machine learning classifier, regression model) to indicate complete pathological response). Nuciforo teaches trastuzumab benefits patients with higher TILs levels and increase TILs at baseline are associated with increased probability of pCR (see discussion, pg. 174). Nuciforo teaches TILs predictive value are strongest at D15 and teaches selecting patients for treatment without anti-HER therapy without chemotherapy (see pg. 175, 2nd column). Nuciforo teaches selecting patients who have a higher change of being cured with a chemo free regiment in HER2 positive early breast cancer (see pg. 176). Nuciforo does not teach expression measurements of CD45.
However it was known in the art to assess TILs by immunohistochemical stain with CD45. Keegan teaches assessing TIL counts using IHC staining with CD45 on FFPE at baseline and 20 days post treatment (claim 17). Keegan additionally teaches RNA libraries were generating for transcriptomic profile of treated pre and on treatment sample pairs, using cell population counter method to measure abundance of immune cell populations (see methods) (multiplex spatial proteomics) (claim 42). Keegan teaches higher TILs are associated with increased likihood of patient achieving a pCR to therapy.
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to improve the method of detecting TILs for determining complete response to therapy in breast cancer, as taught by Nuciforo and include analysis of TILs using known techniques for detection, including expression of CD45 as taught by Keegan. The ordinary artisan would have been motivated to use analysis of CD45 and spatial proteomics in the analysis of Nuciforo because Nuciforo teaches analysis of TILs to determine complete response after administering therapy and Keegan teaches determining complete response of therapy in breast cancer by TILs analysis using CD45 expression staining. Additionally the ordinary artisan would have used spatial proteomics because Keegan teaches analysis of additional markers in determining pCR of TILs in determining breast cancer response following therapy. The ordinary artisan would have been motivated to continue to treat without chemotherapy for subjects with pCR as taught by Nuciforo because Nucuiforo teaches the method allows for selecting subjects for chemotherapy free treatment, as such the ordinary artisan would have treated with targeted HER2 therapy only in subjects determined to have a pCR. The ordinary artisan would have had a reasonable expectation of success that the use of spatial proteomics and analysis of TILs using expression of CD45 could be used in the method of Nuciforo because Keegan teaches analysis of TILs and pCR of on treatment cancer biopsy samples using CD45 analysis and counter method to measure immune cell populations for analysis.
Conclusion
No claims are allowable.
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 SARAE L BAUSCH whose telephone number is (571)272-2912. The examiner can normally be reached M-F 9a-4p.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Fereydoun Sajjadi can be reached at 571-272-3311. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SARAE L BAUSCH/Primary Examiner, Art Unit 1699
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