DETAILED ACTION
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 .
Claims 1-3, 6-8, 11, 12, 15-18, 23, 25, 27, 28, 38, 39, 43, and 44 are pending and currently under consideration.
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.
Claim 12 is 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 12 recites exemplary claim language (see text in parentheses). The metes-and-bounds of the claims are unclear because it is unclear how recited examples limit claims. See MPEP 2173.05(d).
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-3, 6-8, 11, 12, 15-18, 23, 25, 38, and 39 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Factors to be considered in determining whether undue experimentation is required, are summarized in In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988). There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is "undue." These factors include, but are not limited to: the breadth of the claims, the nature of the invention, the state of the prior art, the level of one of ordinary skill, the level of predictability in the art, the amount of direction provided by the inventor, the existence of working examples, and the quantity of experimentation needed to make or use the invention based on the content of the disclosure. See also Ex parte Forman, 230 USPQ 546 (BPAI 1986).
The claims are broadly drawn to methods wherein just any altered amount (such as an increase or a decrease) of DAS, N3AP, and CA125 in just any biological sample from a subject is (i) an indication that the subject harbors or is risk of harboring ovarian cancer, or does not harbor or is not at risk of harboring ovarian cancer, (ii) an indication that the subject is at risk of developing ovarian cancer or not at risk of developing ovarian cancer, (iii) just any indication of just any predisposition of the subject to ovarian cancer, (iv) just any indication of just any likelihood of progression of the ovarian cancer in the subject, (v) just any indication of progression-free survival of the subject, (vi) just any indication of just any likely outcome of treatment of the ovarian cancer, and (vii) just any indication that the subject is a candidate for treatment with just any anticancer therapy. The specification further states a marker may be present in an increased amount or a decreased amount ([0101], in particular). This clearly includes highly-unpredictable contradictory methods, such as methods wherein an elevated amount of DAS, N3AP, and CA125 is equally an indication (i) that a subject harbors or is risk of harboring ovarian cancer and (ii) does not harbor or is not at risk of harboring ovarian cancer.
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 discloses a combination of DAS, N3AP, and CA125 has been used to distinguish early-stage ovarian cancer patients from controls (Example 3, in particular). However, it is unclear which levels of DAS, N3AP, and CA125 are indicative of ovarian cancer. Further, the specification does not demonstrate using the combination of DAS, N3AP, and CA125 to determine risk of developing ovarian cancer, predisposition of ovarian cancer, likelihood of progression of ovarian cancer, likelihood of progression-free survival, likelihood of outcome of any treatment of ovarian cancer.
The level of unpredictability for using a particular level of a particular molecule (or combination of molecules) to detect or characterize a disease state is quite high. The state of the prior art dictates that one of skill in the art would not predict that a level of a particular molecule (or combination of molecules) is indicative of a particular diseased state without a demonstration that said particular diseased stated correlates with said particular level of said particular molecule (or combination of molecules). 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 level of a particular molecule (or combination of molecules) correlating with a particular disease or disease state, one of skill in the art would not predict said particular level of said particular molecule (or combination of molecules) correlates with said particular disease or disease state without undue experimentation. Experimentation to identify such a correlation would in itself be inventive.
In order to perform the broadly claimed methods, undue experimentation would be required to determine which levels of DAS, N3AP, and CA125 are, or are not, (i) an indication that the subject harbors or is risk of harboring ovarian cancer, or does not harbor or is not at risk of harboring ovarian cancer, (ii) an indication that the subject is at risk of developing ovarian cancer or not at risk of developing ovarian cancer, (iii) a particular indication of a particular predisposition of the subject to ovarian cancer, (iv) a particular indication of a particular likelihood of progression of the ovarian cancer in the subject, (v) a particular indication of progression-free survival of the subject, (vi) a particular indication of a particular likely outcome of treatment of the ovarian cancer, and (vii) a particular indication that the subject is a candidate for treatment with of a particular anticancer therapy.
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.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-3, 6-8, 11, 12, 15-18, 23, 25, 38, and 39 are rejected under 35 U.S.C. 101 because the claimed invention is directed to judicial exception(s) (i.e., a law of nature, a natural phenomenon, and/or an abstract idea) without significantly more. Abstract ideas include mathematical concepts (including mathematical relationships, formulas, equations, and calculations), mental processes (including concepts performed in the human mind), and certain methods of organizing human activity (including managing personal behavior, relationships, or interactions between people). The rationale for this determination is explained below:
Claims 1-3, 6-8, 11, 12, 15-18, 23, 25, 38, and 39 are directed to abstract ideas and natural phenomenon because the claims recite natural phenomenon and an abstract idea (“Step 2A prong one”) and the judicial exception(s) is/are not integrated into a practical application (“Step 2A prong two”). The “natural phenomenon” is: an altered amount of DAS, N3AP, and CA125 in a biological sample from a subject is (i) an indication that the subject harbors or is risk of harboring ovarian cancer, or does not harbor or is not at risk of harboring ovarian cancer, (ii) an indication that the subject is at risk of developing ovarian cancer or not at risk of developing ovarian cancer, (iii) just any indication of just any predisposition of the subject to ovarian cancer, (iv) just any indication of just any likelihood of progression of the ovarian cancer in the subject, (v) just any indication of progression-free survival of the subject, (vi) just any indication of just any likely outcome of treatment of the ovarian cancer, and (vii) just any indication that the subject is a candidate for treatment with just any anticancer therapy. The “abstract idea” ideas (all mental processes) include: the “determining”, “predicting”, “diagnosing”, “classifying”, “selecting”, and “comparing” steps of claim 1. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception(s). A claim that focuses on judicial exception(s) can be shown to recite something “significantly more” than the judicial exception(s) by reciting a meaningful limitation beyond the judicial exceptions. However, in the instant case, the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the additional elements (when considered both individually and as an ordered combination) are limited to well-understood, routine and conventional limitations of measuring levels of DAS, N3AP, and CA125 in a biological sample from a subject (“Step 2B”). Well-understood, routine and conventional limitations are not meaningful limitations and are not enough to qualify the claimed method as reciting something “significantly more” than the judicial exception(s) (see Part I.B.1 of the interim Guidance).
MPEP 2106.05(d)(II) provides a non-limiting list of laboratory techniques recognized by courts as well-understood, routine, conventional activity. These techniques include:
i. Determining the level of a biomarker in blood by any means, Mayo, 566 U.S. at 79, 101 USPQ2d at 1968; Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1362, 123 USPQ2d 1081, 1088 (Fed. Cir. 2017);
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Here, the claims do not contain any significant additional elements or steps beyond the observation of judicial exception(s) present when performing routine and conventional methods. Further, the broad instant claims, encompassing correlations that have not been demonstrated with amounts of DAS, N3AP, and CA125, do not relate the judicial exception(s) in a significant way and appear to be a drafting effort designed to monopolize laws of nature in a manner that is antithetical to patent laws. Further, the active method steps are conventional and routine in the art for the reasons stated above and the claims do not amount to significantly more than the judicial exception(s). Further, just as methods comprising detecting paternal DNA sequences in particular samples by PCR was identified in Ariosa v. Sequenom as "well-known, routine, and conventional" (see first paragraph on page 13 of Ariosa Diagnostics, Inc. v. Sequenom, Inc. (Fed. Cir. 2015)) even though the prior art did not demonstrate detecting said paternal DNA sequences in said particular samples by PCR, the methods encompassed by the instant claims are well-known, routine, and conventional. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the additional elements (common methods of detecting expression) are routinely performed in the art to obtain data regarding expression and treat subjects. In regards to “diagnosing" or “providing a prognosis”, it is further noted that merely presenting results of a process otherwise unpatentable under 35 U.S.C. 101 is insufficient to establish eligibility under the statute. See FairWarning IP, LLC v. Iatric Sys., Inc., No. 2015-1985, 2016 WL 5899185, at *3 (Fed. Cir. Oct. 11, 2016) (claim unpatentable under 35 U.S.C. 101 despite recitation of the step: “providing notification if [an] event has occurred”). Moreover, “[w]hile preemption may signal patent ineligible subject matter, the absence of complete preemption does not demonstrate patent eligibility…." Ariosa Diagnostics, Inc., v. Sequenom, Inc., 788 F.3d 1371, 1379 (Fed. Cir. 2015), cert. denied, No. 15-1182, 2016 WL 1117246 (U.S. June 27, 2016). Further, “Groundbreaking, innovative, or even brilliant discovery does not by itself satisfy the § 101 inquiry.” Ass’n for Molecular Pathology v. Myriad Genetics, Inc., 133 S. Ct. 2107, 2117 (2013). The claims do not recite something “significantly more” than the judicial exception(s); rather, the claims “simply inform” the natural phenomenon to one performing routine active method steps and do not amount to significantly more than the judicial exception(s).
Claim Rejections - 35 USC § 101
Claims 27-28 are rejected under 35 U.S.C. 101 because the claimed invention is directed to judicial exception(s) (i.e., a law of nature, a natural phenomenon, and/or an abstract idea) without significantly more. The rationale for this determination is explained below:
Claims 27-28 are directed to natural phenomenon because the claims recite natural phenomenon (“Step 2A prong one”) and the judicial exception(s) is/are not integrated into a practical application (“Step 2A prong two”). The “natural phenomenon” include: a combination/panel of (a) DAS, N3AP, and CA125; or (b) DAS, N3AP, AcSpmd, DiAcSpmd, and Ca125. Recited panels are not markedly different than plasma, which naturally comprises (a) DAS, N3AP, and CA125; or (b) DAS, N3AP, AcSpmd, DiAcSpmd, and Ca125 (see Example 3 of the instant specification, in particular). The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception(s). A claim that focuses on judicial exception(s) can be shown to recite something “significantly more” than the judicial exception(s) by reciting a meaningful limitation beyond the judicial exceptions. However, in the instant case, the claims recite nothing more than (i) combinations of markers that are not markedly different than combinations of the markers naturally found in plasma recited in claim 27 and (ii) the natural phenomenon that the combinations function in a diagnostic manner in claim 28 (“Step 2B”). The natural phenomenon that the combinations function in a diagnostic manner is a judicial exception (natural phenomenon) and is not “beyond” judicial exceptions.
Claim Rejections - 35 USC § 101
Claims 43-44 are rejected under 35 U.S.C. 101 because the claimed invention is directed to judicial exception(s) (i.e., a law of nature, a natural phenomenon, and/or an abstract idea) without significantly more. The rationale for this determination is explained below:
Claims 43-44 are directed to natural phenomenon because the claims recite natural phenomenon (“Step 2A prong one”) and the judicial exception(s) is/are not integrated into a practical application (“Step 2A prong two”). The “natural phenomenon” include: (i) levels of DAS, N3AP, and CA125 are elevated a subject with ovarian cancer and (ii) levels of DAS, N3AP, CA125, AcSpmd, and DiAcSpmd are elevated a subject with ovarian cancer. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception(s). A claim that focuses on judicial exception(s) can be shown to recite something “significantly more” than the judicial exception(s) by reciting a meaningful limitation beyond the judicial exceptions. However, in the instant case, the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the additional elements (when considered both individually and as an ordered combination) are limited to well-understood, routine and conventional limitations of administering just any “anticancer drug”, therapeutic radiation, or surgery to a subject that has ovarian cancer that happens to have elevated levels of DAS, N3AP, CA125, AcSpmd, and/or DiAcSpmd (“Step 2B”). Administering anticancer drugs, therapeutic radiation, or surgery to subjects with ovarian cancer are certainly well-understood, routine, and conventional. Well-understood, routine and conventional limitations are not meaningful limitations and are not enough to qualify the claimed method as reciting something “significantly more” than the judicial exception(s) (see Part I.B.1 of the interim Guidance).
Recited active steps of the claims impose no meaningful limit on the scope of the claims, implicate a relevant pre-existing audience, and are recited at a high level of generality such that substantially all methods of administering just any “anticancer drug”, therapeutic radiation, or surgery to a subject that has ovarian cancer that happens to have elevated levels of DAS, N3AP, CA125, AcSpmd, and/or DiAcSpmd would conventionally and routinely perform such steps. Here, the claims do not contain any significant additional elements or steps beyond the observation of judicial exception(s) present when performing routine and conventional methods. Further, the active method steps are conventional and routine in the art for the reasons stated above and the claims do not amount to significantly more than the judicial exception(s). The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the additional elements (common methods of treating a subject with ovarian cancer) are routinely performed in the art to treat subjects with ovarian cancer. The claims do not recite something “significantly more” than the judicial exception(s); rather, the claims “simply inform” the natural phenomenon to one performing routine active method steps and do not amount to significantly more than the judicial exception(s).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 3, 6-8, 11, 12, 16, 17, 23, 25, 27, 28, and 43 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 7-14, 25, 26, 31, 32, 49-52, and 57 of copending Application No. 19/012572 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because both the pending claims and the instant claims are directed to methods of characterizing, selecting treatments for, and treating ovarian cancer patients by administering the same treatments based on measuring elevated levels of the DAS, N3AP, and CA125 panel of the instant claims in a biological sample from a subject (see copending claim 2, specific treatments of copending claim 25, in particular). Regarding instant claims reciting “serum” as a particular biological sample, [0110] of the copending specification discloses biological samples of the copending method include serum. Regarding instant claim 23 reciting the ovarian cancer is ”early stage”, [032] of the copending specification discloses ovarian cancer of the copending method includes early stage. Copending claims, reciting additional markers in addition to those recited by the instant claims, are directed to species of the instant claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
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/SEAN E AEDER/Primary Examiner, Art Unit 1642