Office Action 2: Final Rejection (2024-09-20)
Rejection types: 101 - Patent-Eligible Subject Matter, 112 - Written Description/Enablement

CLAIMS:
Listing of Claims

Amendments to Claims:

This listing of claims replaces all prior versions and listings of claims in this application.

1\. (Currently Amended) A method of treating a subject who has primary melanoma, wherein the primary melanoma is cutaneous melanoma and is stage Ito IIC, the method comprising:obtaining a biopsy sample from the primary melanoma;
determining the T cell fraction (TCFr) of said sample, wherein determining the TCFr comprises analyzing T-cell receptor beta (TCR p3) gene sequences in substantially every T cell in the sample, and qiuantitating total nucleated cells and calculating the proportion ofT cells in the sample relative to its total number ofnucleated cell; \[\[and\]\] selecting a subject with TCFr below 20% for an aggressive treatment; and
treating said subject with \[\[an\]\] the aggressive treatment, wherein the aggressive treatment is targeted treatment, immunotherapy, chemotherapy, and/or radiation, or a combination thereof

2\. -4. (Cancelled)33

5\. (Currently Amended) The method of claim \[\[4\]\] 1, wherein the primary melanoma is 1-4 mm thick.

6\. -7. (Cancelled)

8\. (Currently Amended) The method of claim \[\[7\]\] 1, wherein said analyzing is performed by high-throughput DNA sequencing.

9\. (Cancelled)
10\. (Currently Amended) The method of claim \[\[9\]\] 1, wherein the chemotherapy comprises administration of one or more nitrosoureas; alkylating agents; microtubule targeting agents;or platinum-containing agentsSVG {EMBED HERE} 0.0770.09

11\. (Currently Amended) The method of claim \[\[9\]\] 1, wherein the targeted treatment comprises a BRAF inhibitor and/or a MEK inhibitor.

12\. (Currently Amended) The method of claim \[\[9\]\] 1, wherein the immunotherapy comprises administration of a checkpoint inhibitor.

13\. (Currently Amended) The method of claim \[\[9\]\] 1, wherein the immunotherapy comprises administration of a vaccine targeting melanoma cells, peptide-based vaccine, viral vector-based vaccine, or dendritic cell vaccine.

14\. (Cancelled)

15\. (Currently Amended) The method of claim 1, further comprising determining one or more of Breslow thickness\[\[;\]\], ulceration status\[\[;\]\], levels of mitoses/mm2\[\[;\]\], and nodal disease in the sample\[\[,\]\]; and treating a subject with the aggressive treatment when the one or more of Breslow thickness, ulceration status;levels of mitoses/mm2, and nodal disease is high in the sample.

OFFICE ACTION:
FINAL ACTION
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 responsive to the Amendments and Reply filed June 20, 2024.  Claims 1, 5, 8, 10-13, and 15 have been amended, and claims 2-4, 6-7, 9, and 14 have been canceled.  Claims 1, 5, 8, 10-13, and 15 remain under consideration.  Applicant’s amendments and arguments have been thoroughly reviewed, and have overcome the prior rejections of claims under 35 USC 112(b) (although the claims remain indefinite for the reasons given below), and under 35 USC 103 (in view of the amendment of claim 1 to recite the type of primary melanoma required, as well as more particular criteria for selecting a subject for “aggressive treatment”).  However, the claims remain rejected for the reasons that follow, which include new grounds of rejection necessitated by Applicant’s amendments.  Any rejections and/or objections not reiterated in this action have been withdrawn.  This action is FINAL.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim Objections
Claims 1, 5, 8, 10-13, and 15 are objected to because of the following informalities: in independent claim 1, at line 7, the claim recites “total number of nucleated cell” rather than “total number of nucleated cells”.  Appropriate correction is required.
Claim Rejections - 35 USC § 112(d)/fourth paragraph
THE FOLLOWING INCLUDES NEW GROUNDS OF REJECTION NECESSITATED BY APPLICANT’S AMENDMENTS
Claim 15 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.  Amended claim 15 recites “treating a subject with the aggressive treatment when” certain conditions are met; however, claim 1 as written, from which claim 15 depends, actually requires that a “treating” step be performed.  As such, claim 15 does not properly depend from claim 1, as the claim encompasses embodiments in which treating is not performed (specifically, in cases when the criteria specified in claim 15 are not met).  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.
Claim Rejections - 35 USC § 112(b)/second paragraph
THE FOLLOWING INCLUDES NEW GROUNDS OF REJECTION NECESSITATED BY APPLICANT’S AMENDMENTS:
Claims 1, 5, 8, 10-13, and 15 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.
The term “high” in claim 15 is a relative term that renders the claim indefinite. The term “high” 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. Accordingly, clarification is required with regard to what would/would not be considered “high” with regard to each of the criteria, or with what a comparison is made in order to establish that a value for one of the criteria is “high”, etc. (although it is also noted that the claim is not properly dependent from claim 1 for the reasons indicated above; thus, both the rejections under 35 USC 112(b) and 35 USC 112(d) should be considered when amending the claim).
Claims 1, 5, 8, and 10-13 are indefinite to the extent that they are directed to embodiments as set forth in dependent claim 15.  Particularly, while the language of independent claim 1 appears to recite a requirement for performing a step of “selecting a subject…for aggressive treatment” and “treating said subject with the aggressive treatment”, dependent claim 15 as written embraces embodiments wherein a treatment identified by the same terminology - “aggressive treatment” - is only performed when additional criteria referenced in that claim are met.  Thus, to the extent that claim 1 and its other dependent claims are directed to such an embodiment, it is unclear what is required by the recitation “treating said subject with the aggressive treatment”, and further clarification (either of claim 1, claim 15, or both) is required.
Claim Rejections - 35 USC § 101
THE FOLLOWING INCLUDES NEW GROUNDS OF REJECTION NECESSITATED BY APPLICANT’S AMENDMENTS:
Claims 1, 5, 8, 10-13, and 15 remain rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more.
Initially, it is noted that this rejection applies to claims 1, 5, 8, and 10-13 to the extent that they are directed to embodiments in which performance of the recited “aggressive treatment” is not actually required, as is suggested by the language of dependent claim 15 (see also the above rejections under 35 USC 112(d) and 35 USC 112(b)).
Claim 15 recites the activity of “treating a subject with the aggressive treatment when the one or more of Breslow thickness, ulceration status, levels of mitoses/mm2, and nodal disease is high” in a sample.  This conditional limitation encompasses embodiments in which an active “treating” is performed, as well as embodiments in which - based on the results of a prior data gathering activity - a decision could be made to take no further action, i.e., a mental activity that may be performed entirely in the human mind, which is a type of abstract idea.  The judicial exception is not integrated into a practical application because the only clearly required active steps of the claims are data gathering steps that amount to insignificant extra-solution activity.  The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because these data gathering steps, whether considered individually or in combination, were well-understood, routine and conventional at the time of applicant’s invention (as evidenced by the teachings of Tarhini et al [previously cited]); the inclusion of these steps in the claims thus does not add anything significantly more than a judicial exception.  Thus, claim 15 - and to the extent that they are directed to the embodiment of claim 15, claims 1, 5, 8, and 10-13 - is/are not directed to patent eligible subject matter.  With further regard to claim 5, this claim is further limiting only of the source of material for data gathering, which does not impart any kind of practical application or add anything more than a JE.   The activities of claim 8 are a more particular type of data gathering known in the art, as evidenced by Tarhini et al.  Regarding claims 10-13, it is reiterated that this rejection applies to the claims to the extent that they do not require performance of the “aggressive treatment” (which again, is in question because of the language of applicant’s claims).
The reply of June 20, 2024 traverses the prior rejection of claims under 35 USC 101 for the following reasons.
The reply summarizes the prior rejection and the language of independent claim 1 as amended (Reply page 12), and urges that amended claim 1 does not recite a conditional limitation, but rather active steps of “selecting a subject with TCFr below 20% for an aggressive treatment” and “treating said subject with the aggressive treatment”, such that the “treatment” of the claim “integrates any alleged judicial exception into a practical application” (Reply at page 12 bridging to page 13).
These arguments have been thoroughly considered but are not persuasive, because - as is indicated in the above rejections - the amended claims (and particularly claim 15, as well as claims 1, 5, 8, and 10-13 as directed to embodiments as set forth in claim 15) do not clearly necessarily require performance of the recited “aggressive treatment” in the manner referenced in claim 1.  Accordingly, given the actual language of the claims under consideration, the rejection must be maintained.
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 extension fee 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 date of this final action.

APPLICANT REBUTTAL: REMARKS Status of the Claims Claims 1, 5, 8, 10-13, and 15 were pending in this application. These claims were examined, and stand rejected. Claim 1 is presently amended to fix a minor typographical error at line 7. Claim 15 is presently cancelled without prejudice or disclaimer. These amendments are fully supported by the original claims and the specification as originally filed. No new matter has been added by these claim amendments. Upon entry of these amendments, claims 1, 5, 8, and 10-13 will be pending in this application. Reexamination and reconsideration of the claims are respectfully requested in view of these amendments and the following remarks. Interview Summary Applicant thanks Examiner Johannsen for the courtesy of the telephonic conversations on November 25, 2024 and December 3, 2024, with Applicant's representative. During the conversations, the outstanding rejections under 35 U.S.C. §§§ 112(d), 112(b), and 101 were discussed and it was agreed upon that cancelling claim 15 will overcome these rejections. Claim Objections Claims 1, 5, 8, 10-13, and 15 were objected to because of informalities. In particular, the Office noted that, "in independent claim 1, at line 7, the claim recites "total number of nucleatedcell" rather than "total number of nucleated SVG {EMBED HERE} 0.1430.473 Applicant thanks the Office for noting this typographical error and has amended independent claim 1 accordingly. In view of the foregoing, this objection may be withdrawn. Claim Rejections - 35 U.S.C. & 112(d) Claim 15 was rejected under 35 U.S.C. § 112(d) as allegedly 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. In particular, the Office alleged (Office Action at page 3): Amended claim 15 recites "treating a subject with the aggressive treatment when" certain conditions are met; however, claim 1 as written, from which claim 15 depends, actually requires that a "treating" step be performed. As such, claim 15 does not properly depend from claim 1, as the claim encompasses embodiments in which treating is not performed (specifically, in cases when the criteria specified in claim 15 are not met). Without acquiescing to the rejection and solely in furtherance of prosecution, Applicant has cancelled claim 15, thus rendering this rejection moot. Claim Rejections - 35 U.S.C. 4 112(b) Claims 1, 5, 8, 10-13, and 15 were rejected under 35 U.S.C. § 112(b) as allegedly indefinite. In particular, the Office alleged (Office Action at page 4): The term "high" in claim 15 is a relative term that renders the claim indefinite. The term "high" 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... Claims 1,5, 8, and 10-13 are indefinite to the extent that they are directed to embodiments as set forth in dependent claim 15. Particularly, while the language of independent claim 1 appears to recite a requirement for performing a step of "selecting a subject...for aggressive treatment" and "treating said subject with the aggressive treatment", dependent claim 15 as written embraces embodiments wherein a treatment identified by the same terminology - "aggressive treatment" - is only performed when additional criteria referenced in that claim are met. Thus, to the extent that claim 1 and its other dependent claims are directed to such an embodiment, it is unclear what is required by the recitation "treating said subject with the aggressive treatment", and further clarification (either of claim 1, claim 15, or both) is required. Claim 15 is presently cancelled. As agreed upon during the Examiner Interview (see, "Interview Summary" above), cancellation of claim 15 would be sufficient to overcome this rejection. Reconsideration and withdrawal of the rejection of claims 1, 5, 8, and 10-13 (claim 15 is presently cancelled, rendering all rejections directed to this claim moot) under 35 U.S.C. § 112(b) is kindly requested in view of the foregoing. Claim Rejections - 35 U.S.C. 4 101 The Office maintained the rejection of claims 1, 5, 8, 10-13, and 15 under 35 U.S.C. § 101 as allegedly directed to an abstract idea without significantly more. In particular, the Office alleged (Office Action at page 5): Initially, it is noted that this rejection applies to claims 1, 5, 8, and 10-13 to the extent that they are directed to embodiments in which performance of the recited "aggressive treatment" is not actually required, as is suggested by the language of dependent claim 15 (see also the above rejections under 35 USC 112(d) and 35 USC 112(b)). Claim 15 is presently cancelled. As agreed upon during the Examiner Interview (see, "Interview Summary" above), cancellation of claim 15 would be sufficient to overcome this rejection. Reconsideration and withdrawal of the rejection of claims 1, 5, 8, and 10-13 (claim 15 is presently cancelled, rendering all rejections directed to this claim moot) under 35 U.S.C. § 101 is kindly requested in view of the foregoing. CONCLUSION It is believed that all rejections of the pending claims have been addressed. However, the absence of a reply to a specific rejection, issue or comment does not signify agreement with or concession of that rejection, issue or comment. In addition, because the arguments made above may not be exhaustive, there may be reasons for patentability of any or all pending claims (or other claims) that have not been expressed. Finally, nothing in this paper should be construed as intent to concede any issue with regard to any claim, except as specifically stated in this paper, and the amendment of any claim does not necessarily signify concession of unpatentability of the claim prior to its amendment. In view of the preceding arguments and amendments, the claims are believed to be in condition for allowance. If a discussion would be helpful to move the case forward, the Examiner is invited to call the undersigned at the telephone number provided below. A Request for Continued Examination with the requisite fees is being concurrently filed herewith. Apply those fees and any other necessary charges or credits to Deposit Account 06-1050, referencing the above attorney docket number. Respectfully submitted, Date: December 19, 2024 /Pallavi Banerjee/ Pallavi Banerjee, Reg. No. 81,012Customer Number 26161Fish & Richardson P.C. Telephone: +1 (617) 521-7023 Facsimile: (877) 769-7945 24440200.doc

NEXT OFFICE ACTION: Attachment to Notice of Allowability – Examiner’s Comment
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection.  Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.  Applicant's submission filed on December 19, 2024 - in which dependent claim 15 was canceled, and independent claim 1 amended to address an objection - has been entered.  As all remaining issues have been overcome (please see the Interview Summary mailed December 9, 2024), claims 1, 5, 8, and 10-13 are now allowed.
In accordance with 37 CFR 1.126, the allowed claims will be renumbered as claims 1-7 in the issued patent.
Conclusion