Case 1:17-cv-12194-MLW Document 32-7 Filed 03/01/18 Page 1 of 11
`Case 1:17-cv—12194-MLW Document 32-7 Filed 03/01/18 Page 1 of 11
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`EXHIBIT 7
`EXHIBIT 7
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`

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`Case 1:17-cv-12194-MLW Document 32-7 Filed 03/01/18 Page 2 of 11
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`IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
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`PATENT
`Attorney Docket No. 37901-713.304
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`In re application of:
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`Confirmation No.: 9266
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`Inventors: Daniel D. VON HOFF et al.
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`Group Art Unit: 1631
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`Serial No.: 14/170,466
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`Filed: January 31, 2014
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`Examiner: Lin, Jerry
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`Customer No. 96600
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`For: SYSTEM AND METHOD FOR
`DETERMINING INDIVIDUALIZED MEDICAL
`INTERVENTION FOR A DISEASE STATE
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`ELECTRONICALLY FILED AUGUST 22, 2014
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`Mail Stop Amendment
`Commissioner for Patents
`P.O. Box 1450
`Alexandria, VA22313-1450
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`RESPONSE TO FINAL OFFICE ACTION
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`Sir/Madam:
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`Introductory Comments:
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`This communication is in response to the Final Office Action mailed on July 29, 2014 (the
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`"Office Action"). The shortened statutory period for response expires on October 29, 2014. Therefore,
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`Applicants believe no fee is required with the filing of this Response.
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`Applicants respectfully request consideration of the above-referenced application in view of the
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`following amendments and remarks.
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`Amendments to the Claims begin on page 2 of this paper.
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`Remarks begin on page 4 of this paper.
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`Attorney Docket No. 37901-713.304
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`

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`Case 1:17-cv-12194-MLW Document 32-7 Filed 03/01/18 Page 3 of 11
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`U.S. Serial No. 14/170,466
`Response to Office Action mailed July 29, 2014
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`Amendments to the Claims:
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`1.
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`(Currently Amended) A system for generating a report identifying at least one therapeutic agent
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`for an individual with a cancer comprising:
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`a.
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`at least one device configured to assay a plurality of molecular targets in a biological sample
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`to determine individualized molecular profile test values for the plurality of molecular targets,
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`wherein the molecular targets comprise EGFR, KIT, TOPI, MLHI, PTEN, PDGFRA and
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`ESRI; and
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`b. at least one computer database comprising:
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`1. a reference value for the plurality of molecular targets; and
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`11. a listing of available therapeutic agents for said plurality of molecular targets;
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`c.
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`a computer-readable program code comprising instructions to input the individualized
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`molecular profile test values and to compare said test values with a corresponding reference
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`value in (b )(i);
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`d. a computer-readable program code comprising instructions to access the at least one
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`computer database and to identify at least one therapeutic agent from the listing of available
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`therapeutic agents for the plurality of molecular targets wherein said comparison to said
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`reference in ( c) indicates a likely benefit of the at least one therapeutic agent; and
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`e.
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`a computer-readable program code comprising instructions to generate a report that
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`comprises a listing of the molecular targets wherein said comparison to said reference
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`indicated a likely benefit of the at least one therapeutic agent in ( d) along with the at least one
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`therapeutic agent identified in ( d).
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`2.
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`(Previously Presented) The system of claim 1, wherein the individualized molecular profile test
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`values are input into the system from a location that is remote from said at least one database.
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`3.
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`(Previously Presented) The system of claim 1, wherein the individualized molecular profile test
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`values are input into the system over an internet connection.
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`4.
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`(Original) The system of claim 1, wherein the report is in electronic or paper format.
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`5.
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`(Currently Amended) The system of claim 1, wherein the at least one computer database further
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`comprise§. data corresponding to at least one clinical trial of a molecular target.
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`-2-
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`Attorney Docket No. 37901-713.304
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`Case 1:17-cv-12194-MLW Document 32-7 Filed 03/01/18 Page 4 of 11
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`U.S. Serial No. 14/170,466
`Response to Office Action mailed July 29, 2014
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`6.
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`(Original) The system of claim 1, wherein the reference value for each of the plurality of
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`molecular targets comprises a nucleic acid and/or protein.
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`7.
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`(Previously Presented) The system of claim 1, wherein the test values for the plurality of
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`molecular targets in the individual are determined after the individual has received drug therapy
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`for the cancer.
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`8.
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`(Previously Presented) The system of claim 1, wherein the molecular profile test values are
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`determined by assessing a cell, tissue sample, blood sample or combination thereof.
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`9.
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`(Previously Presented) The system of claim 1, wherein the molecular profile test values are
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`determined by performing a test for a gene and/ or a protein.
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`10. (Previously Presented) The system of claim 1, wherein the reference is obtained from at least one
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`normal individual without the cancer.
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`11. (Currently Amended) The system of claim 1, wherein the individual has been treated by and
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`failed to respond to ~ ffile cancer therapeutic.
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`12. (Currently Amended) The system of claim 1, wherein the individual has been treated by and
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`failed to respond to mofe thffii at least one cancer therapeutic.
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`13. (Previously Presented) The system of claim 1, wherein the at least one device configured to assay
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`the plurality of molecular targets is configured to perform at least one of immunohistochemistry
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`(IHC), an expression microarray, a comparative genomic hybridization (CGH) microarray, a
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`single nucleotide polymorphism (SNP) microarray, a fluorescent in-situ hybridization (FISH), in(cid:173)
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`situ hybridization (ISH), and a proteomic array.
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`14. (Previously Presented) The system of claim 1, wherein the at least one device configured to assay
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`the plurality of molecular targets is configured to perform at least one of a microarray, genotyping
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`and proteomic analysis.
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`-3-
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`Attorney Docket No. 37901-713.304
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`Case 1:17-cv-12194-MLW Document 32-7 Filed 03/01/18 Page 5 of 11
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`U.S. Serial No. 14/170,466
`Response to Office Action mailed July 29, 2014
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`REMARKS
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`With this Response, claims 1, 5 and 11-12 are amended for clerical purposes only. Applicants
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`respectfully request entry thereof and reconsideration of the application in view of the amendments and
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`arguments below.
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`I.
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`Examiner Interview
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`Applicants are appreciative to Examiner Lin for attending the phone interview held August 14,
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`2014 with Applicants' representatives Ramin Akhavan and Jeff Thomas. Arguments to address the
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`outstanding rejections under 35 U.S.C. § 101 were discussed. The Examiner's comments were very
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`helpful in the preparation of this Response.
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`II.
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`Information Disclosure Statement
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`Applicants respectfully request that the Examiner acknowledge the Information Disclosure
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`Statement uploaded via EFS-WEB on July 3, 2014. A supplemental Information Disclosure Statement is
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`also uploaded with this Response.
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`III.
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`Final Office Action I Advisory Action
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`With this Response, Applicants believe that all claims are in order for allowance. However, if the
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`Examiner should disagree, Applicants request that the current Office Action be made non-final as
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`Applicants believe that the rejection under 35 U.S.C. § 101 in regards to natural phenomena is a new
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`rejection not necessitated by amendment. See Office Action, Item 4, pp. 3-4.
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`Should the Examiner disagree that all claims are in order for allowance yet maintain the finality
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`of the Office Action, Applicants request that the Examiner issue an Advisory Action as this Response is
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`submitted within two months of the mailing date of the Office Action. No additional search is required.
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`IV.
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`Rejection under 35 U.S.C. § 101: Abstract Idea
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`The Examiner rejected claims 1-14 under 35 U.S.C. § 101 as allegedly directed to non-statutory
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`subject matter. Office Action, Item 3, p. 2. The Examiner states that the instant claims are "as a whole,
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`considering all claim elements both individually and in combination, do not amount to significantly more
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`than an abstract idea." Id. The Examiner maintained this rejection from the prior office action and further
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`states that "Applicants have stated that the inclusion of an assay in the preamble demonstrates that there is
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`-4-
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`Attorney Docket No. 37901-713.304
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`Case 1:17-cv-12194-MLW Document 32-7 Filed 03/01/18 Page 6 of 11
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`U.S. Serial No. 14/170,466
`Response to Office Action mailed July 29, 2014
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`more than a generic computer. .. However, the instant claims contain no recitation of performing the
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`assay. Thus, it does not appear that a particular machine is necessary for the claimed invention." Id. at p.
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`3.
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`Applicants disagree with the Examiner's assertion that the claims are an abstract idea, for at least
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`the reason that the claims provide improvements to another technology or technical field, e.g., by
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`improving the treatment of cancer victims. See Alice Corp. Ply. Ltd v. CLS Bank Int 'l, 573 U.S._
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`(2014) (Slip Op. at p. 15) (distinguishing abstract claims from those that "effect an improvement in any
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`other technology or technical field," citing Diamond v. Diehr, 450 U. S. 175, 177-78 (1981 )).
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`Furthermore, the claims recite at least one device configured to assay a plurality of specific molecular
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`targets comprising EGFR, KIT, TOPI, MLHl, PTEN, PDGFRA and ESRl and thereby obtain
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`individualized molecular profile test values. This device is not found in the preamble but rather is recited
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`in claim 1 (a). The device is also configured to assay the particular panel of molecular targets, which panel
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`the Examiner has acknowledged is non-conventional in the context of the claimed invention. Moreover,
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`the claimed system comprises code to input the individualized molecular profile test values obtained
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`using the device, to compare such test values to a reference, and to generate a report based on such
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`comparison. Thus, the device is a necessary and integral part of the claimed invention.
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`Accordingly, the claimed invention provides improvements to another technology or technical
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`field, recites machinery other than a generic computer, and further recites that such machinery is
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`configured to assay a non-conventional panel of targets. Such elements ensure that the claims amount to
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`significantly more than the alleged abstract idea itself and that the claims are not abstract. Applicants
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`respectfully request that the Examiner reconsider and withdraw this rejection.
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`V.
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`Rejection under 35 U.S.C. § 101: Natural Phenomena
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`The Examiner newly rejected claims 1-14 under 35 U.S.C. § 101 as allegedly directed to non(cid:173)
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`statutory subject matter in regards to natural phenomena. Office Action, Item 4, p. 3. The Examiner states
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`that "the instant claims are drawn to comparing molecular profiles to reference values and identifying a
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`therapeutic agent. However, the association between a molecular profile[] to reference values and
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`therapeutic agents is a natural phenomenon." Id. The Examiner alleges that "[s]uch a natural phenomenon
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`is a judicial exception and is not patent eligible. Furthermore, the step of obtaining the data via an assay is
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`an extrasolution activity that does not provide a practical application of the judicial exception." and
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`concludes that the "instant claims are non-statutory." Id. Applicants respectfully traverse this rejection.
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`-5-
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`Attorney Docket No. 37901-713.304
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`Case 1:17-cv-12194-MLW Document 32-7 Filed 03/01/18 Page 7 of 11
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`U.S. Serial No. 14/170,466
`Response to Office Action mailed July 29, 2014
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`On March 4, 2014, the USPTO issued guidance for determining subject matter eligibility in view
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`of Mayo Collaborative Services v. Prometheus Laboratories, Inc., 566 U.S._ (2012) ("Mayo") and
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`Association for Molecular Pathology v. Myriad Genetics, Inc., 569 U.S._ (2013) ("Myriacf'). See 2014
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`Procedure For Subject Matter Eligibility Analysis Of Claims Reciting Or Involving Laws Of
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`Nature/Natural Principles, Natural Phenomena, And/Or Natural Products (the "Guidance"). The Guidance
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`directs the Examiner to perform a three step inquiry to determine subject matter eligibility. If the claimed
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`invention is directed to a category of statutory patent-eligible subject matter (Question 1) and there is any
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`question whether the claims recite or involve one or more judicial exceptions (Question 2), the claims are
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`assessed under Question 3, which asks whether the claims as a whole recite something significantly
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`different than the judicial exception(s )? Id. at p. 3. The Guidance presents a number of factors to consider
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`in regards to Question 3, which factors are to be weighed according to the totality of the circumstances to
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`determine subject matter eligibility. Id. at pp. 4-5. Because the instant claims are directed to a patent
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`eligible system and may involve a natural phenomenon (i.e., "association between a molecular profiles to
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`reference values and therapeutic agents"), Applicants herein assess the claimed invention under Question
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`3. This analysis reveals that the claimed invention is significantly different than the alleged natural
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`phenomenon and is thus patent eligible.
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`a. Factors weighing towards eligibility (significantly different) indicate that the
`claimed invention recites patentable subject matter
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`Factors weighing toward eligibility include the following. See Guidance at p. 4.
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`(a) Claim is a product claim reciting something that initially appears to be a natural
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`product ...
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`This factor is not relevant.
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`(b) Claim recites elements/steps in addition to the judicial exception(s) that impose
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`meaningful limits on claim scope, i.e., the elements/steps narrow the scope of the claim so that others are
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`not substantially foreclosed from using the judicial exception(s).
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`There are numerous elements of the claimed invention that would not foreclose others from the
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`alleged natural phenomenon. For example, one need not employ a system comprising the claimed assay
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`device, particular databases, and particular code elements to associate molecular profiles to reference
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`values and therapeutic agents. Furthermore, one need not assess the particular panel of claimed targets,
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`i.e., EGFR, KIT, TOPI, MLHI, PTEN, PDGFRA and ESRI to obtain a molecular profile for a cancer.
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`For example, the targets could be assessed individually or in alternate panels.
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`-6-
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`Attorney Docket No. 37901-713.304
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`

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`Case 1:17-cv-12194-MLW Document 32-7 Filed 03/01/18 Page 8 of 11
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`U.S. Serial No. 14/170,466
`Response to Office Action mailed July 29, 2014
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`Applicants' dependent claims recite further elements that one need not employ to associate
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`molecular profiles to reference values and therapeutic agents, including but not limited to remote access
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`(claims 2-3), particular report format (claim 4), clinical trial database (claim 5), particular type of
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`reference (claims 6, 10), particular treatment regimen (claims 7, 11-12), particular sample type (claim 8),
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`particular assay or assay device (claims 9, 13, 14 ).
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`Thus, this factor weighs towards eligibility.
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`( c) Claim recites elements/steps in addition to the judicial exception(s) that relate to the
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`judicial exception in a significant way, i.e., the elements/steps are more than nominally, insignificantly, or
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`tangentially related to the judicial exception(s).
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`The claims recite elements that are not tangential to the alleged natural phenomenon. For
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`example, the system comprises code to utilize the results of the assay for the particular panel of targets
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`obtained using the assay device. Furthermore, the system comprises code to directly associate molecular
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`profiles to reference values and therapeutic agents. See, e.g., claim l(d).
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`Thus, this factor weighs towards eligibility.
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`( d) Claim recites elements/steps in addition to the judicial exception(s) that do more than
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`describe the judicial exception(s) with general instructions to apply or use the judicial exception(s).
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`The claimed invention comprises numerous elements that provide more than just general
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`instructions to apply the alleged natural phenomenon. For example, the claims are limited to a system
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`having numerous concrete elements, such as an assay device, databases, program code logic, and
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`particular panel of markers.
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`Thus, this factor weighs towards eligibility.
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`( e) Claim recites elements/steps in addition to the judicial exception(s) that include a
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`particular machine or transformation of a particular article, where the particular
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`machine/transformation implements one or more judicial exception(s) or integrates the judicial
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`exception(s) into a particular practical application.
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`As described above, the device is a necessary and integral part of the claimed invention. The
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`device is further configured to transform a biological sample to determine the individualized molecular
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`profile test values. Thus, this factor weighs towards eligibility.
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`(f)
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`Claim recites one or more elements/steps in addition to the judicial exception(s) that add
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`a feature that is more than well-understood, purely conventional or routine in the relevant field.
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`-7-
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`Attorney Docket No. 37901-713.304
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`

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`Case 1:17-cv-12194-MLW Document 32-7 Filed 03/01/18 Page 9 of 11
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`U.S. Serial No. 14/170,466
`Response to Office Action mailed July 29, 2014
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`By withdrawing the prior rejection under 35 U.S.C. § 103, the Examiner has acknowledged that
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`molecular profiling of Applicants' claimed selection of biomarkers to guide drug selection for cancer was
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`neither routine nor conventional at the time of filing. Accordingly, this factor weighs towards eligibility.
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`b. Factors weighing against eligibility (not significantly different) indicate that the
`claimed invention recites patentable subject matter
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`Factors weighing against eligibility include the following. See Guidance at pp. 4-5.
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`(g) Claim is a product claim reciting something that initially appears to be a natural
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`product ...
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`This factor is not relevant.
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`(h) Claim recites elements/steps in addition to the judicial exception(s) at a high level of
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`generality such that substantially all practical applications of the judicial exception(s) are covered.
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`As explained above under factor (b ), the claimed invention recites elements that do not
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`substantially foreclose others from using the alleged natural phenomena. Thus, this factor weighs towards
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`eligibility.
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`(i) Claim recites elements/steps in addition to the judicial exception(s) that must be
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`used/taken by others to apply the judicial exception(s).
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`As with factor (h) above, the claimed invention recites several elements that need not be
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`employed by others to apply the alleged judicial exception. For example, Applicants' claims are directed
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`to profiling a combination of biomarkers. One need not assess this particular combination in order to
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`apply the alleged natural principle. For example, one may link expression of less than all of the recited
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`biomarkers to a drug efficacy. In addition, one need not employ a system comprising the claimed assay
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`device, particular databases, and particular code elements to associate molecular profiles to reference
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`values and therapeutic agents.
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`Applicants' dependent claims recite further elements that one need not employ to associate
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`molecular profiles to reference values and therapeutic agents, including but not limited to remote access
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`(claims 2-3), particular report format (claim 4), clinical trial database (claim 5), particular type of
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`reference (claims 6, 10), particular treatment regimen (claims 7, 11-12), particular sample type (claim 8),
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`particular assay or assay device (claims 9, 13, 14 ).
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`Thus, this factor weighs towards eligibility.
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`-8-
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`Attorney Docket No. 37901-713.304
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`

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`Case 1:17-cv-12194-MLW Document 32-7 Filed 03/01/18 Page 10 of 11
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`U.S. Serial No. 14/170,466
`Response to Office Action mailed July 29, 2014
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`G) Claim recites elements/steps in addition to the judicial exception(s) that are well(cid:173)
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`understood, purely conventional or routine in the relevant field.
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`As with factor (f) above, the Examiner has acknowledged that Applicants selection ofbiomarkers
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`is neither routine nor conventional. Thus, this factor weighs towards eligibility.
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`(k) Claim recites elements/steps in addition to the judicial exception(s) that are insignificant
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`extra-solution activity, e.g., are merely appended to the judicial exception(s).
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`As explained above in regard to factors ( c) and ( d), the claimed invention recites several elements
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`that integrate the alleged natural phenomenon into the claims and thus are more than extra-solution
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`activity.
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`Thus, this factor weighs towards eligibility.
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`(1) Claim recites elements/steps in addition to the judicial exception(s) that amount to
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`nothing more than a mere field of use.
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`As explained above, the claimed invention recites several concrete and non-conventional
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`elements in addition to the alleged natural phenomenon. These elements limit the claim to a particular
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`application of linking biomarker expression to therapeutic response.
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`Thus, this factor weighs towards eligibility.
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`c. Conclusion: Claimed invention recites patentable subject matter
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`In sum, analysis of the factors in the Guidance reveals that all relevant factors weigh towards
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`subject matter eligibility. Indeed, Applicants' claimed combination of biomarkers to inform selection of a
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`therapeutic agent for cancer is neither routine nor conventional. Nor does the claimed invention preempt
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`the alleged natural phenomenon. For at least these reasons, Applicants respectfully request that the
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`Examiner reconsider and withdraw this rejection.
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`VI.
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`Non-Statutory Double Patenting
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`The Examiner provisionally rejected claims 1-12 on the ground of non-statutory double patenting
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`as being unpatentable over claims 1-10 of co-pending Application No. 14/150,624 (hereinafter "the '624
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`application"). Office Action, p. 5. The Examiner alleges that "[a]lthough the claims at issue are not
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`identical, they are not patentably distinct from each other because the instant claims require all the
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`limitations of the copending application with the additional limitations of specifying EGFR, KIT, TOPI,
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`MLHl, PTEN, PDGRA, and ESRl as molecular targets." Id.
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`-9-
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`Attorney Docket No. 37901-713.304
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`

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`Case 1:17-cv-12194-MLW Document 32-7 Filed 03/01/18 Page 11 of 11
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`U.S. Serial No. 14/170,466
`Response to Office Action mailed July 29, 2014
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`Although Applicants believe the claims are patentably distinct, Applicants submit a terminal
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`disclaimer herewith to obviate the provisional double patenting rejection over the co-pending '624
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`application in order to expedite the allowance of all claims.
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`CONCLUSION
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`Applicants submit that this paper fully addresses the Final Office Action mailed July 29, 2014.
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`Applicants believe that the pending claims are under condition for allowance. Should the Examiner have
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`any questions, the Examiner is encouraged to telephone the undersigned at (571) 261-9809. The
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`Commissioner is authorized to charge any additional fees which may be required, including petition fees
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`and extension of time fees, to Deposit Account No. 50-4961 (Docket No.: 37901-713.304).
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`Respectfully submitted,
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`CARIS MPI, INC.
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`/Ramin Akhavan/
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`Ramin Akhavan
`Registration No. 58,120
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`Date: August 22, 2014
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`Caris MPI, Inc.
`6655 N. MacArthur Blvd.
`Irving, TX 75039
`Customer No. 96600
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`-10-
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`Attorney Docket No. 37901-713.304
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