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 .
Continued Examination Under 37 CFR 1.114
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 November 7, 2025 has been entered.
Claims Status and Response to Amendments
The amendments filed November 7, 2025 have been acknowledged and entered. Claims 16 and 25-32 are pending.
Withdrawn Rejections
Applicant is notified that any outstanding rejection or objection that is not expressly maintained in this Office Action has been withdrawn or rendered moot in view of Applicant' s amendments and/or
remarks.
Claim Rejections - 35 USC § 112a
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 16 and 25-32 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 wherein COC1 ACC is indicated by explicit threshold levels of G0S2 methylation and BUB1B-PINK1 expression scores which are recited in the specification does not reasonably provide enablement for wherein COC1 ACC is indicated by any level of G0S2 methylation and BUBIB-PINKI expression score. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims
The point at issue is that the specification fails to define which levels of G0S2 methylation and BUBIB-PINKI expression score are indicative of COC1 ACC and therefore fails to teach how to use the claimed invention. Step b of claim 16 requires administering linsitinib when a subject has a G0S2 methylation and BUBIB-PINKI expression score that is indicative of COC1 ACC; however, the specification fails to define which methylation or expression scores are indicative of the condition. Given the direction provided by Applicant, one skilled in the art could not practice the full scope of the invention without undue and unreasonable experimentation.
As a general rule, enablement must be commensurate with the scope of claim language.MPEP 2164.08 states, "The Federal Circuit has repeatedly held that "the specification must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation." In re Wright, 999 F.2d 1557, 1561, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)" (emphasis added). The "make and use the full scope of the invention without undue experimentation" language was repeated in 2005 in Warner-Lambert Co. v. Teva Pharmaceuticals USA Inc., 75 USPQ2d 1865, and Scripps Research Institute v. Nemerson, 78 USPQ2d 1019 asserts: "A lack of enablement for the full scope of a claim, however, is a legitimate rejection." The principle was explicitly affirmed most recently in Liebel-Flarsheim Co. v. Medrad, Inc., 481 F.3d 1371, 82 USPQ2d 1113; Auto. Tech. Int'l, Inc. v. BMWofN. Am., Inc., 501 F.3d 1274, 84 USPQ2d 1108 (Fed. Cir. 2007), Monsanto Co. v. Syngenta Seeds, Inc., 503 F.3d 1352, 84 U.S.P.Q.2d 1705 (Fed. Cir. 2007), and Sitrick v. Dreamworks, LLC, 516 F.3d 993, 85 USPQ2d 1826 (Fed. Cir. 2008).
In evaluating the enablement question, several factors are to be considered. Note In re Wands, 8 USPQ2d 1400 and Ex parte Forman, 230 USPQ 546. The factors include: 1) The nature of the invention, 2) the state of the prior art, 3) the predictability or lack thereof in the art, 4) the amount of direction or guidance present, 5) the presence or absence of working examples, 6) the breadth of the claims, and 7) the quantity of experimentation needed. The determination that “undue experimentation” would have been needed to make and use the claimed invention is not a single, simple factual determination. Rather, it is a conclusion reached by weighing all the above noted factual considerations.
The nature of the invention & breadth of claims:
The claims are drawn to a method a method for identifying a subject with adrenocortical carcinoma (ACC) as having COC1 ACC comprising
a) identifying the subject as having COC1 ACC by obtaining or having obtained a sample from the subject; and measuring the level of GOS2 methylation and BUBIB-PINKI expression score in the sample; and
b) administering linsitinib to said subject when said subject has a level of G0S2 methylation and BUBIB-PINKI expression score indicative of the presence of COCl ACC.
The claims however do not require that level of G0S2 methylation and BUBIB-PINKI expression score are any particular threshold. The scope of the claims therefore includes wherein any threshold level is indicative of COC1 ACC.
The state of the prior art
The state of the prior art is not aware of all levels of G0S2 methylation and BUB1B-PINK1 expression score that are indicative of COC1 ACC. Moreover, a person skilled in the art recognizes that diagnosis of disease based on such parameters as epigenetic status (DNA methylation) and gene expression requires validation (some sort of positive control) to show that certain thresholds are indicative of a particular disease. There is no evidence in the record or state of the prior art which teaches the specific levels of G0S2 methylation and BUB1B-PINK1 expression that indicate COC1 ACC.
The Level of One of Ordinary Skill
The level of skill in the art is high. The artisan using the claimed invention would be a person with medical training such as a medical doctor or physician with an MD degree or the equivalent.
Predictability in the art
The art is highly unpredictable. In the field of diagnostics, determining the presence of disease (e.g. COC1 ACC) by measuring biochemical parameters such as expression levels or methylation status requires validation to show that such levels are actually indicative of the disease in question. One cannot simply predict which levels of protein expression or methylation status will be indicative of a condition.
Amount of guidance/working examples
Applicant teaches specific expression levels of BUB1B-PINK and methylation levels of G0S2 are indicative of COC1 ACC (see page 24). Applicant, however, fails to teach the full scope of expression and methylation levels that indicate the disease. The invention is a method of identifying a subject as having COC1 ACC by measuring the level of GOS2 methylation and BUBIB-PINKI expression score in the sample; however, how is a person skilled in the art expected to practice the method if they do not know which threshold levels of BUB1B-PINK expression and G0S2 methylation indicate that a subject has COC1 ACC? As the Supreme Court said in Brenner v. Manson, 148 USPQ at 696: “a patent is not a hunting license. It is not a reward for the search, but compensation for its successful conclusion.” As U.S. Court of Customs and Patent Appeals stated In re Diedrich 138 USPQ at 130, quoting with approval from the decision of the board: “We do not believe that it was the intention of the statutes to require the Patent Office, the courts, or the public to play the sort of guessing game that might be involved if an applicant could satisfy the requirements of the statutes by indicating the usefulness of a claimed compound in terms of possible use so general as to be meaningless and then, after his research or that of his competitors has definitely ascertained an actual use for the compound, adducing evidence intended to show that a particular specific use would have been obvious to men skilled in the particular art to which this use relates.”
The quantity of experimentation needed:
MPEP 2164.01(a) states, "A conclusion of lack of enablement means that, based on theevidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)."
That conclusion is clearly justified here and one skilled in the art could not practice the full scope of the claimed invention without undue and unreasonable experimentation.
Claim Rejections - 35 USC § 112b
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.
Claims 16 and 25-32 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. [A] claim is indefinite when the boundaries of the protected subject matter are not clearly delineated and the scope is unclear (MPEP 2173.04). The following terms and/or phrases render the scope of the claims unclear because the specification does not provide a scope limiting definition of the phrase or term, or any direction for ascertaining the scope of the limitation indicated by the term or phrase. Accordingly, one skilled in the art could not ascertain the metes and bounds of the claimed invention.
Claim 16 recites the limitation “indicative of the presence of COC1 ACC” which is indefinite because the specification provides no threshold cutoffs or definition of G0S2 methylation and BUB1B-PINK1 expression score that is indicative of the condition. The specification teaches at page 24 that
the expression levels of BUB1B and PINKl and the methylation levels of G0S2 are used to classify COC into subtypes COCl-3 and explicitly recites the present disclosure is not limited to particular cut-off or threshold values for characterizing ACC. How is a person skilled supposed to know what levels and scores are indicative of COC1 ACC in order to practice the claimed method? MPEP 2173 states 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph requires that a patent application 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 primary purpose of this requirement of definiteness of claim language is to ensure that the scope of the claims is clear so the public is informed of the boundaries of what constitutes infringement of the patent. Based on the direction provided by Applicant, a person skilled in the art would not be able to determine the metes and bounds of the invention, and thus what constitutes infringement, because the specification does not clearly define what level of G0S2 methylation and BUB1B-PINK1 expression score is indicative of the presence of COC1 ACC.
Claims 25-32 depend from claim 16 and do not clarify the above deficiency.
Applicant should amend the claim to clearly define what levels of G0S2 methylation and BUB1B-PINK1 expression indicate COC1 ACC.
Conclusion
No claim is allowed.
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December 29, 2025
/K.S.M./Examiner, Art Unit 1624
/BRUCK KIFLE/Primary Examiner, Art Unit 1624