DETAILED ACTION
Notice of AIA Status
The instant application, filed on or after 16 March 2013, is being examined under the first inventor to file provisions of the Leahy-Smith America Invents Act (AIA ).
Status of the Claims
The listing of claims filed 26 August 2025 has been examined. Claims 1–12 are pending. Claims 1 and 2 are amended. Claims 3, 7, 8, 11, and 12 are canceled.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 15 June 2022; 13 December 2023; and 20 August 2025 are acknowledged and have been considered.
Reply to Restriction Requirement and Election of Species
Applicant’s election without traverse of Group I in the reply filed 26 August 2025 is acknowledged.
Applicant’s election of species without traverse of compound 63,
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, is also acknowledged.
Scope of Search and Examination
A prior art search and examination will begin with the elected species. (MPEP § 803.02). If no prior art is found that would anticipate or render obvious the elected species, then the search will be extended to other species of the elected group. If no prior art is found that would anticipate or render obvious the elected group, then the search will be extended to non-elected species in non-elected groups. If prior art is found that anticipates or renders obvious a non-elected species or group, then the search will stop and the Markush-type claim will be rejected. The prior art search will not be extended unnecessarily to cover all non-elected species. (Id.).
Modified Unity of Invention—Restriction Requirement
Applicant’s elected species has been searched and is free of the prior art.
The search was expanded to elected Group I, Chemical Formula 1, as amended in claim 1. Chemical Formula 1 was searched and is free of the prior art. Therefore, claims 1 and 2 are allowable.
The search was expanded to Group II, Chemical Formula 2, in claim 3. Chemical Formula 2 was searched and is free of the prior art. Therefore, claim 3 is allowable.
The restriction requirement between Group I, directed to Chemical Formula 1, wherein R1 is a tetrahydroisoquinoline, and Group II, directed to Chemical Formula 2, is hereby withdrawn as to any claim that requires all the limitations of allowable claims 1–3.
The restriction requirement between Group I, directed to Chemical Formula 1, wherein R1 is other than a tetrahydroisoquinoline as presented in the original claim 1, and Group II, directed to Chemical Formula 2, is maintained.
Advisory
In view of the above noted withdrawal of the restriction requirement between Group I, directed to Chemical Formula 1, wherein R1 is a tetrahydroisoquinoline, and Group II, directed to Chemical Formula 2, Applicant is advised that if any claim presented in a divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application.
Once a restriction requirement is withdrawn, the provisions of 35 U.S.C. § 121 are no longer applicable. In re Ziegler, 443 F.2d 1211, 1215 (CCPA 1971); MPEP § 804.01.
Objections to the Specification
The abstract of the disclosure is objected to because it recites language referring to the purported merits (“novel”) and phrases that can be implied (“The present invention”).
Appropriate correction is required.
For guidelines for the preparation of patent abstracts, see MPEP § 608.01(b) (Explaining: The abstract should be in narrative form and avoid legal phraseology (e.g., means, said), terms referring to purported merits of the invention (e.g., new, novel), and phrases that can be implied (e.g., The disclosure concerns, The disclosure defined by this invention,). The language should be clear and concise, and not repeat information given in the title. It should not compare the invention with the prior art. The abstract is generally limited to a single paragraph within the range of 50 to 150 words in length.).
Claim Rejections - 35 U.S.C. § 112
The following is a quotation of 35 U.S.C. § 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 4 is rejected under 35 U.S.C. § 112(d) as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 4 depends from claim 1, which has been amended so R1 is tetrahydroisoquinoline.
Claim 4 includes compounds in which R1 is other than tetrahydroisoquinoline. As such, claim 4 fails to incorporate by reference all the limitations of claim 1 and is therefore an improper dependent claim.
Appropriate correction is required.
Examiner recommends deleting any compounds not within the scope of claim 1.
Claim Rejections - 35 U.S.C. § 112
The following is a quotation 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.
Claims 5–12 are rejected under 35 U.S.C. § 112(a) because 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 the claims.
MPEP § 2164.01(a) explains how enablement for the claimed invention can be analyzed:
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.” . . . These factors include, but are not limited to:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
The Wands factors are analyzed with respect to the claimed invention in turn below.
The breadth of the claim is broad in scope, as it extends to treating or preventing cancer, narcolepsy, or fasciitis. Cancer is a genus of diseases that includes the numerous types of cancer recited in claims 6, 8, 10, and 12.
The nature of the invention generally relates to the pharmaceutical art and more specifically to a compound of formulae 1 or 2, a pharmaceutical composition thereof, a method of making the compound, and a method of administering the compound to a subject. Certain compounds exhibit inhibitory activity against TRIB2 or YAP. (Spec., ¶¶ 775–782). Thus, the nature of the invention is sophisticated.
The state of the prior art is in its infancy for preventing cancer, narcolepsy, or fasciitis. Generally, in order to prevent a disease, one of skill in the art would need to identify the subjects likely to acquire such as disease, carry out the claimed invention (e.g., administer the claimed compound/composition), and demonstrate the subject did not have any cells infected by the pathogen and/or demonstrate the subject did not develop the disease as a result of the administration of the compound/composition. Examiner is unaware of evidence from the prior art that supports a claim for preventing cancer, narcolepsy, and/or fasciitis.
The level of one of ordinary skill may be found by inquiring into: (i) the type of problems encountered in the art; (ii) prior art solutions to those problems; (iii) the rapidity with which innovations are made; (iv) the sophistication of the technology; and (v) the education level of active workers in the field. Custom Accessories, Inc. v. Jeffrey-Allan Industries, Inc., 807 F.2d 855, 962 (Fed. Cir. 1986). All of the factors may not be present in every case, and one or more of them may predominate. Envtl. Designs, Ltd. v. Union Oil Co., 713 F.2d 693, 696 (Fed. Cir. 1983). Based on the typically high education level of workers in the pharmaceutical art and the high degree of sophistication required to solve problems encountered in the art, Examiner finds a person having ordinary skill in the art would have at least a college degree in chemistry, biology, biochemistry, pharmacology, or a related field, and several years of experience.
The level of predictability in the art is generally unpredictable. The relevant art requires each potential drug candidate to be assessed for physiological activity. In re Fisher, 427 F.2d 833, 166 USPQ 18, 24 (CCPA 1970). The more unpredictable an area is the more specific disclosure is necessary to satisfy the statutory requirement. MPEP § 2164.02(II) explains that a correlation between the claimed invention and the evidence provided in an application, along with a correlation between the evidence and the models recognized in the art, are required:
“Correlation” as used herein refers to the relationship between in vitro or in vivo animal model assays and a disclosed or a claimed method of use. An in vitro or in vivo animal model example in the specification, in effect, constitutes a “working example” if that example “correlates” with a disclosed or claimed method invention. If there is no correlation, then the examples do not constitute “working examples.” In this regard, the issue of “correlation” is also dependent on the state of the prior art. In other words, if the art is such that a particular model is recognized as correlating to a specific condition, then it should be accepted as correlating unless the examiner has evidence that the model does not correlate. Even with such evidence, the examiner must weigh the evidence for and against correlation and decide whether one skilled in the art would accept the model as reasonably correlating to the condition. In re Brana, 51 F.3d 1560, 1566, 34 USPQ2d 1436, 1441 (Fed. Cir. 1995) (reversing a USPTO decision based on finding that in vitro data did not support in vivo applications).
Further, treatments may be effective for some subjects and ineffective for other subjects. Thus, each candidate for pharmaceutical or veterinary medicine must be evaluated on its own even when a nexus to an existing drug or class of drugs has been established.
The amount of direction provided by the inventor is limited to an in vitro evaluation of the compounds of Formulae 1 and 2. Certain compounds exhibit inhibitory activity against TRIB2 or YAP. (Spec., ¶¶ 775–782).
The existence of working examples relate to in vitro screening of the compounds of Formulae 1 and 2. There are no examples demonstrating preventing a specific disease with a TRIB2 or YAP inhibitor.
The quantity of experimentation needed to make or use the invention based on the content of the disclosure is extensive, as it includes in vitro and in vivo screening for each specific disease or disorder encompassed by the claims.
Scope of Enablement Conclusion
In view of the Wands factors discussed above, the disclosure of the instant application does not reasonably enable a person having ordinary skill in the art to use the full scope of the claimed invention. The breadth of the claims is broad in scope; the nature of the invention is sophisticated; the state of the prior art is in its infancy for preventing cancer, narcolepsy, or fasciitis; the level of skill in the art is high; the pharmaceutical art is unpredictable; the direction provided by the inventor is limited to in vitro evaluation of the compounds of Formulae 1 and 2 for activity against TRIB2 or YAP; and the quantify of experimentation needed to practice the claimed invention is extensive. Thus, when the evidence is considered as a whole, undue experimentation would be required to practice the full scope of the claimed invention.
Examiner recommends amending the claims to delete the term prevention.
Conclusion
Claims 1–3 are allowed.
Claims 4–12 are rejected.
Communication
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jason Nolan at (571) 272-2480. The examiner can normally be reached Monday through Friday between 9:00–5:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Adam Milligan, can be reached on 571-270-7674.
The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JASON M. NOLAN/Patent Examiner, Art Unit 1623
/ADAM C MILLIGAN/Supervisory Patent Examiner, Art Unit 1623