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 .
Response to Amendment
The amendment filed January 8th, 2026 is acknowledged. Regarding the Office Action mailed October 8th, 2025:
The rejection set forth under 35 U.S.C. 102 is withdrawn in view of the amendments.
The rejection set forth under 35 U.S.C. 103 is withdrawn in view of the amendments.
New grounds of rejection are set forth below, as necessitated by the amendments.
Claim Summary
Claims 1-2, 5-6, 11, 15-16, 18-20, 23, 27, 31-32, 38-39, and 45 have been amended. Claims 3-4, 9-10, 13, 21-22, 24-25, 28-30, 33-34, 37, and 40-44 have been canceled. Claims 1-2, 5-8, 11-12, 14-20, 23, 26-27, 31-32, 35-36, 38-39, and 45 are pending. Claims 8, 20, 31, 38-39, and 45 are withdrawn from consideration as being drawn to a non-elected invention/species. Claims 1-2, 5-7, 11-12, 14-19, 23, 26-27, 32, and 35-36 are under examination and discussed in this Office action.
Claim Rejections - 35 USC § 112(a) – New – Necessitated by Amendment
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 1-2, 5-7, 11-12, 14-19, 23, 26-27, 32, and 35-36 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 a Cas13a polypeptide of LbuCas13a or LwaCas13a and an RNA reporter, does not reasonably provide enablement for any Type VI CRISPR-Cas nuclease and any reporter nucleic acid as embraced by the claims. 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.
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.” See MPEP § 2164. 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, the quantity of experimentation needed to make or use the invention based on the content of the disclosure.
The office has analyzed the specification in direct accordance to the factors outlines in In re Wands. MPEP 2164.04 states: “[W]hile the analysis and conclusion of a lack of enablement are based on factors discussed in MPEP 2164.01(a) and the evidence as whole, it is not necessary to discuss each factor in written enablement rejection.” These factors will be analyzed, in turn, to demonstrate that one of ordinary skill in the art would have had to perform “undue experimentation” to make and/or use the invention and therefore, applicant’s claims are not enabled.
(A) With respect to the breadth of the claims: Claim 1 as currently drafted encompasses a composition comprising a Type VI Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)- associated (Cas) nuclease and a reporter nucleic acid. “Type VI CRISPR-Cas nuclease” does not limit the nuclease in question to the LbuCas13a or LwaCas13a nucleases as described in the specification. Furthermore, “a reporter nucleic acid” does not limit the reporter in question to the RNA reporter as described in the specification. Consequently, the breadth of the claim is expansive. Claims 2, 5-7, 11-12, 14-19, 23, 26-27, 32, and 35-36 encompass the same breadth as claim 1 since they either do not limit the Type VI CRISPR-Cas nuclease to a LbuCas13a or LwaCas13a nuclease or do not limit the reporter nucleic acid to an RNA reporter.
(B) The nature of the invention: The invention is in the field of CRISPR-Cas nuclease compositions directed to target single-stranded deoxyribonucleic acid (ssDNA).
(C), (D), (E) With respect to the state of the prior art, the level of one of ordinary skill and predictability of the art: Freije (Detect and destroy: CRISPR-based technologies for the response against viruses, Cell Host Microbe, April 2021, 29, 689-703) teaches on Cas13 proteins specifically cleaving single-stranded RNA (Page 691, column 1, paragraph 2). Freije further teaches that Cas13 (e.g. Type VI CRISPR-Cas nuclease) collaterally cleaves ssRNA (Page 691, column 1, paragraph 4), which has been used for detection techniques like SHERLOCK to generate a signal from a synthetic, fluorescent ssRNA when a target RNA is present (Page 692, column 1 paragraph 5 to column 2, paragraph 1).
Zhou (CRISPR/Cas-based nucleic acid detection strategies: Trends and challenges, February 2024, 10, 1-20) also supports the same teachings, where Cas13 proteins specifically cleave single-stranded RNA (Page 5, paragraph 2; Page 13, paragraph 3) and Cas13 collaterally cleaves ssRNA (Page 5, paragraph 2; Page 13, paragraph 4), which can be used for detection techniques like SHERLOCK to generate a signal when a target RNA is present (Figure 5).
Taken together, the art supports the use of RNA targets and RNA reporters with Type VI CRISPR-Cas nucleases. A composition comprising a DNA target interacting with a Type VI CRISPR-Cas nuclease beyond those nucleases described in the specification, and any reporter nucleic acid besides the RNA reporters described in the specification, remains highly unpredictable.
The invention is drawn to biological molecules, and is therefore 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 level of skill in the art is therefore deemed to be high.
(F), (G) With respect to the amount of direction and working examples provided by the applicant: While the Applicant has provided description of many Type VI CRISPR-Cas nucleases (see paragraphs [0101]-[0104], Table 1, and Table 2) the provided working examples are only directed to the Cas13a polypeptides LbuCas13a or LwaCas13a. As seen in Figure 2C, Figure 4B, paragraph [0175], and paragraph [0178], these two Cas13a polypeptides are capable of use without an RNA polymerase through direct detection of ssDNA. With regard to reporter nucleic acids, the Applicants have directly stated at Page 121, paragraph [0177]: “Results indicated the Cas13 trans-cleavage was specific for RNA reporters, even when activated by target ssDNA.”
The Applicants have not provided working examples comprising any other Type VI CRISPR-Cas nucleases. Given the state of the art, as cited above, Type VI CRISPR-Cas nucleases are known to interact with target RNA as opposed to target ssDNA, and more evidence would be required to enable further Type VI CRISPR-Cas nucleases in the composition. Furthermore, the Applicants have not provided working examples to reporter nucleic acids capable of use in this composition besides RNA reporters. In fact, the Applicants’ instant disclosure specifically shows that at least DNA reporters do not work with Type VI CRISPR-Cas nucleases (see paragraph [0176] and [0177] and Figure 3).
(H) Undue experimentation would be required to practice the invention as claimed due to the amount of experimentation necessary because of the expansive breadth of the claims, the state of the prior art and its high predictability, and the limited amount of guidance in the form of varied working examples in the specification. A skilled artisan recognizes that any Type VI CRISPR-Cas nuclease and any reporter nucleic acid are distinct from the Cas13a polypeptides LbuCas13a or LwaCas13a and an RNA reporter, and thus applicability of the claimed method to any Type VI CRISPR-Cas nuclease and any reporter nucleic acid as embraced by the claim remains unpredictable, requiring undue experimentation. For example, multiple compositions comprising each different Type VI CRISPR-Cas nuclease would have to be prepared and tested for their ability to form a complex directly with a target ssDNA. Furthermore, multiple compositions comprising each type of reporter nucleic acid (including but not limited to DNA, locked nucleic acids, peptide nucleic acids, and chimeric nucleic acids) would have to be prepared and tested for their ability to interact with the claimed nuclease. Thus, the quantity of experimentation in this area would be extremely large since there are a significant number of parameters that would have to be studied. Furthermore, the ultimate outcome of such experimentation is completely unpredictable.
MPEP §2164.01(a), 4th paragraph, provides that, “A conclusion of lack of enablement means that, based on the evidence 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 1157, 1562; 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).
Genentech Inc. v. Novo Nordisk A/S, 42 USPQ2d 1001, 1005 (CA FC), states that, “[p]atent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable,” citing Brenner v. Manson, 383 U.S. 519, 536 (1966) (stating, in the context of the utility requirement, that “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion”). The Genentech decision continued, “tossing out the mere germ of an idea does not constitute enabling disclosure. While every aspect of a generic claim certainly need not have been carried out by an inventor, or exemplified in the specification, reasonable detail must be provided in order to enable members of the public to understand and carry out the invention.” Id. at p. 1005.
After applying the Wands factors and analysis to claims 1-2, 5-7, 11-12, 14-19, 23, 26-27, 32, and 35-36, in view of the applicant’s entire disclosure, and considering the In re Wright, In re Fisher and Genentech decisions discussed above, it is concluded that the practice of the full scope of the invention as claimed would not be enabled by the written disclosure. Therefore, claims 1-2, 5-7, 11-12, 14-19, 23, 26-27, 32, and 35-36 are rejected under 35 U.S.C. §112(a) for failing to disclose sufficient information to enable a person of skill in the art to practice the claimed invention to it the full scope embraced by the claims.
Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
US20210102242, US20210078002 and US20220325363 were all considered given their earlier effective filing date. However, given that the same inventive entities as in the instant case are associated with these references, they are not considered to serve as prior art.
Conclusion
All claims stand rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Allison E Schloop whose telephone number is (703)756-4597. The examiner can normally be reached Monday-Friday 8:30-5 ET.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Anne Gussow can be reached at (571) 272-6047. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ALLISON E SCHLOOP/Examiner, Art Unit 1683
/ANNE M. GUSSOW/Supervisory Patent Examiner, Art Unit 1683