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
The Amendments and Remarks filed 8/17/26 in response to the Office Action of 4/28/26 are acknowledged and have been entered.
Claims 2-9 and 11-20 are pending.
Claims 2, 3, 6, 7, 9, 11-13, and 20 have been amended by Applicant.
Claims 2-9 and 11-20 are currently under examination.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
The following Office Action contains NEW GROUNDS of rejections Necessitated by Amendments.
Rejections Withdrawn
The rejections under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, are withdrawn.
Rejections Maintained
Claim Rejections - 35 USC § 112
Claims 2, 4, 5, and 7 remain rejected and claims 3, 6, 8, 9, and 11-20 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for determining a predicted response score that predicts a subject with NSCLC or melanoma will respond and/or benefit from combination therapy comprising an anti-PD-1 checkpoint inhibitor and an HDAC inhibitor, wherein the predicted response score is (1) low expression of both HDAC1 and HDAC2 in a tumor tissue sample from the subject or (2) a low ratio of combined HDAC1 and HDAC2 expression / combined HDAC3 and HDAC5 expression in a tumor tissue sample from the subject, does not reasonably provide enablement for determining a predicted response score that predicts a subject with NSCLC or melanoma will respond and/or benefit from combination therapy comprising an anti-PD-1 checkpoint inhibitor and an HDAC inhibitor, wherein the predicted response score is (1) low expression of both HDAC1 and HDAC2 in just any l sample from the subject or (2) a low ratio of combined HDAC1 and HDAC2 expression / combined HDAC3 and HDAC5 expression in just any sample from the subject. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to perform the invention commensurate in scope with these claims.
Factors to be considered in determining whether undue experimentation is required are summarized in Ex parte Forman, 230 USPQ 546 (BPAI 1986). They include the nature of the invention, the state of the prior art, the relative skill of those in the art, the amount of direction or guidance disclosed in the specification, the presence or absence of working examples, the predictability or unpredictability of the art, the breadth of the claims, and the quantity of experimentation which would be required in order to practice the invention as claimed.
The instant claims are drawn to determining a predicted response score that predicts a subject with NSCLC or melanoma will respond and/or benefit from combination therapy comprising an anti-PD-1 checkpoint inhibitor and an HDAC inhibitor, wherein the predicted response score is (1) low expression of both HDAC1 and HDAC2 in just any l sample from the subject or (2) a low ratio of combined HDAC1 and HDAC2 expression / combined HDAC3 and HDAC5 expression in just any sample from the subject. This includes methods of determining scores, using HDAC expression results from just any sample from a subject, that have yet to be shown to correlate with response and/or benefit to a recited combination therapy.
This invention is in a class of invention which the CAFC has characterized as "the unpredictable arts such as chemistry and biology". Mycogen Plant Sci., Inc. v. Monsanto Co., 243 F.3d 1316, 1330 (Fed. Cir. 2001).
The specification demonstrates determining a predicted response score that predicts a subject with NSCLC or melanoma will respond and/or benefit from combination therapy comprising an anti-PD-1 checkpoint inhibitor and an HDAC inhibitor, wherein the predicted response score is (1) low expression of both HDAC1 and HDAC2 in a tumor tissue sample from the subject or (2) a low ratio of combined HDAC1 and HDAC2 expression / combined HDAC3 and HDAC5 expression in a tumor tissue sample from the subject (Examples 2-4, in particular).
The level of unpredictability for using an expression pattern to detect any disease state (such as responsiveness or efficacy of treatment) is quite high. The state of the prior art dictates that one of skill in the art would not predict that a particular expression pattern is indicative of a particular diseased state without a demonstration that said particular diseased state correlates with said particular expression pattern. For example, Tockman et al (Cancer Res., 1992, 52:2711s-2718s) teach considerations necessary in bringing a cancer biomarker (intermediate end point marker) to successful application. Absent evidence demonstrating a particular expression pattern correlating with a particular diseased state, one of skill in the art would not predict said particular expression pattern correlates with said particular diseased state without undue experimentation. Experimentation to identify such a correlation would in itself be inventive.
One cannot extrapolate the teachings of the specification to the scope of the claims because the claims are broadly drawn to a method of determining a predicted response score that predicts a subject with NSCLC or melanoma will respond and/or benefit from combination therapy comprising an anti-PD-1 checkpoint inhibitor and an HDAC inhibitor, wherein the predicted response score is (1) low expression of both HDAC1 and HDAC2 in just any l sample from the subject or (2) a low ratio of combined HDAC1 and HDAC2 expression / combined HDAC3 and HDAC5 expression in just any sample from the subject, and Applicant has not enabled said method because it has not been shown that a recited response score determined in just any a biological sample from a subject is indicative of response to a combination therapy comprising a checkpoint inhibitor and an HDAC inhibitor.
Further, undue experimentation would be required to determine which biological samples encompassed by the claims can be predictably used by the claimed method to determine response scores that correlate (or do not correlate) with responsiveness to combination treatment with a checkpoint inhibitor and an HDAC inhibitor in NSCLC and melanoma patients in order to perform the method as broadly claimed.
In view of the teachings above and the lack of guidance, workable examples and or exemplification in the specification, it would require undue experimentation by one of skill in the art to determine with any predictability, that the method would function as claimed.
Response to Arguments
In the Reply of 8/17/26, Applicant argues claims have been amended to be commensurate in scope with exactly the subject matter the examiner acknowledged the specification enables.
The amendments to the claims and the arguments found in the Reply of 8/17/26 have been carefully considered, but are not deemed persuasive. In regards to the argument claims have been amended to be commensurate in scope with exactly the subject matter the examiner acknowledged the specification enables, the examiner disagrees. The 4/28/26 indicated the claims are enabled for methods using tumor tissue sample from a subject with NSCL or melanoma, while the pending claims are drawn to methods using just any sample from a subject with NSCLC or melanoma.
New Rejections Necessitated by Amendments
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 5 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 5 does not further limit the subject matter of claim 2. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Samira Jean-Louis can be reached at (571)270-3503. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SEAN E AEDER/Primary Examiner, Art Unit 1642
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