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 .
Status of the application
Claims 1-23 are pending. This application is a 371 of PCT/US2023/067520, filed on 05/26/2023 and claims foreign priority as a continuation-in-part to PCTCN2023092571, filed on 05/06/2023.
Claim Rejections
Nonstatutory Obviousness-Type Double Patenting
Claims 1–6 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-5, 7, 9, 11-17, and 20-22 of Application No. 18/797,835.
Claims 1–6 of the instant application are not patentably distinct from the allowed claims of Application No. 18/797,835 because both claim sets are directed to the same core inventive concept: selecting and screening multiplex stem-loop reverse transcription primer combinations for simultaneous quantification of multiple miRNAs by varying anchor length, determining multi-specificity, and optionally repeating the screening/modification process until a suitable primer combination is identified.
Claims 7–18 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-5, 7, 9, 11-17, and 20-22 of Application No. 18/797,835.
Claims 7–18 recite the same core method of screening multiplex reverse transcription primer combinations for quantifying multiple miRNAs simultaneously, including selection of stem-loop sequences, selection of anchor sequence lengths, screening for multi-specificity, and optional repeat testing or sensitivity testing. The additional limitations recited in these claims, including hybridization/extension detail, qPCR amplification detail, Ct-value reporting, and specific target-miRNA panels, do not render the claims patentably distinct from the allowed claims of Application No. 18/797,835.
Claims 19–23 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-5, 7, 9, 11-17, and 20-22 of Application No. 18/797,835.
Claims 19–23 recite another formulation of the same screening method, including selecting stem-loop reverse transcription primers, performing RT-qPCR-based screening, determining multi-specificity, and modifying primer anchor lengths when multi-specificity is not confirmed. These claims are not patentably distinct from the allowed claims of Application No. 18/797,835 because they recite the same essential subject matter in alternative wording and/or broader form.
Although the instant claims omit or rearrange certain limitations present in Application No. 18/797,835, those differences do not patentably distinguish the claimed subject matter. The instant claims recite the same basic assay workflow and the same essential screening logic as the claims allowed in Application No. 18/797,835.
35 U.S.C. § 112(a), First Paragraph, Enablement
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 1–6 are rejected under 35 U.S.C. 112(a), or pre-AIA 35 U.S.C. 112, first paragraph, as failing to comply with the enablement requirement.
The claims are broadly drawn to methods for screening multiplex stem-loop reverse transcription primer combinations for quantifying multiple miRNAs simultaneously, including providing target miRNAs, providing stem-loop reverse transcription primers, selecting stem-loop sequences and anchor lengths, screening for multi-specificity, and modifying primer combinations until a successful combination is identified. The scope of the claims is broad and encompasses a wide range of target miRNAs and primer combinations.
The specification does not reasonably enable the full scope of the claimed subject matter without undue experimentation. The disclosure provides only a limited number of working examples involving a small number of human miRNA panels and specific assay conditions, together with general guidance for primer and probe design. The specification does not teach how to identify, optimize, and validate workable multiplex stem-loop primer combinations across the full breadth of the claimed scope.
The standard for determining whether the specification meets the enablement requirement was established in the Supreme Court decision of Minerals Separation Ltd. v. Hyde, 242 U.S. 261, 270 (1916) which postured the question: is the experimentation needed to practice the invention undue or unreasonable? See also In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988). Accordingly, even though the statute does not use the term "undue experimentation," it has been interpreted to require that the claimed invention be enabled so that any person skilled in the art can make and use the invention without undue experimentation. See MPEP § 2164.06 for discussion of quantity of experimentation, including determining reasonableness of experimentation. See also United States v. Telectronics, Inc., 857 F.2d 778, 785, 8 USPQ2d 1217, 1223 (Fed. Cir. 1988) ("The test of enablement is whether one reasonably skilled in the art could make or use the invention from the disclosures in the patent coupled with information known in the art without undue experimentation."). A patent need not teach, and preferably omits, what is well known in the art. In re Buchner, 929 F.2d 660, 661, 18 USPQ2d 1331, 1332 (Fed. Cir. 1991); Hybritech, Inc. v. Monoclonal Antibodies, Inc., 802 F.2d 1367, 1384, 231 USPQ 81, 94 (Fed. Cir. 1986), cert. denied, 480 U.S. 947 (1987); and Lindemann Maschinenfabrik GMBH v. American Hoist & Derrick Co., 730 F.2d 1452, 1463, 221 USPQ 481, 489 (Fed. Cir. 1984). Any part of the specification can support an enabling disclosure, even a background section that discusses, or even disparages, the subject matter disclosed therein. Callicrate v. Wadsworth Mfg., Inc., 427 F.3d 1361, 77 USPQ2d 1041 (Fed. Cir. 2005)(discussion of problems with a prior art feature does not mean that one of ordinary skill in the art would not know how to make and use this feature). Determining enablement is a question of law based on underlying factual findings. In re Vaeck, 947 F.2d 488, 495, 20 USPQ2d 1438, 1444 (Fed. Cir. 1991); Atlas Powder Co. v. E.I. du Pont de Nemours & Co., 750 F.2d 1569, 1576, 224 USPQ 409, 413 (Fed. Cir. 1984).
In order to determine compliance with the enablement requirement of 35 U.S.C. 112(a), the Federal Circuit developed a framework of factors in In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), referred to as the Wands factors to assess whether any necessary experimentation required by the specification is "reasonable" or is "undue." Consistent with Amgen Inc. et al. v. Sanofi et al., 598 U.S. 594, 2023 USPQ2d 602 (2023), the Wands factors continue to provide a framework for assessing enablement in a utility application or patent, regardless of technology area. See Guidelines for Assessing Enablement in Utility Applications and Patents in View of the Supreme Court Decision in Amgen Inc. et al. v. Sanofi et al., 89 FR 1563 (January 10, 2024). These factors include, but are not limited to:
Breadth of the claims: the claims encompass a broad genus of target miRNAs and corresponding primer combinations.
Nature of the invention: multiplex miRNA primer screening and RT-qPCR quantification is sequence-dependent and sensitive to primer interactions.
State of the art/predictability: the specification itself recognizes that multiplex primer interactions are challenging.
The level of predictability in the art: is not considered predictable in this art, in part, due to the complexities of multiplex primer interactions.
Amount of direction provided: the disclosure gives general design principles, but not sufficient guidance to practice the full scope of the claims without substantial trial-and-error.
Working examples: the examples are limited to a small number of specific human miRNA sets and do not demonstrate that the full claimed scope can be practiced without undue experimentation.
The quantity of experimentation needed to make or use the invention based on the content of the disclosure: would be considered excessive given the variable discussed above.
Accordingly, claims 1–6 are not enabled over the full scope of the claimed subject matter.
Claims 7–18 are rejected under 35 U.S.C. 112(a), or pre-AIA 35 U.S.C. 112, first paragraph, as failing to comply with the enablement requirement.
Claims 7–18 are similarly broad and recite the same general multiplex screening methodology, with additional limitations relating to RT-qPCR amplification steps, probe and primer selection, quantification results, and sensitivity testing. Under the Wands factors, the specification provides only limited examples and general design guidance. It does not reasonably enable the full scope of the claims without undue experimentation.
Although the specification includes working examples for two specific human miRNA panels and provides illustrative reaction conditions and sequence listings, the disclosure does not establish that the full range of claimed target miRNAs and primer combinations can be screened and optimized successfully across the entire breadth of the claims without substantial experimentation.
Claims 19–23 are rejected under 35 U.S.C. 112(a), or pre-AIA 35 U.S.C. 112, first paragraph, as failing to comply with the enablement requirement.
Claims 19–23 recite the screening method in another formulation, including RT-qPCR-based screening, multi-specificity determination, and repeat modification of primer anchor lengths. The claims remain broad with respect to the target miRNAs, the primer combinations, and the conditions under which multi-specificity is confirmed.
The specification does not reasonably enable the full scope of these claims without undue experimentation for the same reasons set forth above. The disclosure is limited to a few concrete examples and generalized design guidance, and it does not teach how to practice the claimed method across the full breadth of the genus encompassed by the claims. Under the Wands factors, the specification provides only limited examples and general design guidance. It does not reasonably enable the full scope of the claims without undue experimentation.
Conclusion
For the reasons set forth above, claims 1–23 are rejected under nonstatutory obviousness-type double patenting over claims 1-5, 7, 9, 11-17, and 20-22 of Application No. 18/797,835, and claims 1–23 are further rejected under 35 U.S.C. § 112(a) for lack of enablement.
No Claim is allowed.
Contact information
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GARY BENZION, Ph.D.
Supervisory Patent Examiner
Art Unit 1681
/GARY BENZION/ Supervisory Patent Examiner, Art Unit 1681
