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 1-13 are pending in the instant application. Claims 11-13 are rejected. Claims 1-10 are allowed.
Information Disclosure Statements
The information disclosure statements filed on August 1, 2023 and August 16, 2024 have been considered and signed copies of form 1449 are enclosed herewith.
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 11-13 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.
Enablement is considered in view of the Wands factors (MPEP 2164.01 (A)). These include: nature of the invention, breadth of the claims, guidance of the specification, the existence of working examples, state of the art, predictability of the art and the amount of experimentation necessary. All of the Wands factors have been considered with regard to the instant claims, with the most relevant factors discussed below.
The state of the prior art and the predictability or lack thereof in the art
The term “prevention” actually means to anticipate or counter in advance, to keep from happening, etc. and there is no disclosure as to how one skilled in the art can reasonably establish the basis and the type of subject to which the instant compounds can be administered in order to have the “preventative” effect.
The state of the prior art is that the pharmacological art involves screening in vitro and in vivo to determine which compounds exhibit the desired pharmacological activities (i.e., what compounds can treat or prevent which specific disease by what mechanism). There is no absolute predictability even in view of the seemingly high level of skill in the art. The existence of these obstacles establishes that the contemporary knowledge in the art would prevent one of ordinary skill in the art from accepting any therapeutic regimen on its face.
The instant claimed invention is highly unpredictable as discussed below: It is noted that the pharmaceutical art is unpredictable, requiring each embodiment to be individually assessed for physiological activity. In re Fisher, 427 F.2d 833, 166 USPQ 18 (CCPA 1970) indicates that the more unpredictable an area is, the more specific enablement is necessary in order to satisfy the statue. In the instant case, the claimed invention is highly unpredictable since one skilled in the art would recognize that in regards to therapeutic effects, whether or not the kinase-mediated disease is affected by the administration of a compound of Formula 1 or a pharmaceutically acceptable salt thereof would make a difference.
With regards to the prevention or treatment of the broad classes of disorders or diseases, such as kinase-mediated diseases, inflammatory disorders, cardiovascular disease, virus induced disease, circulatory system disease, and fibroproliferative disease, these methods could include many unrelated disorders or diseases (i.e., many of which have a different cause and, therefore, require a different treatment). There is not one class of compounds, let alone one compound, which can treat or prevent all of the disorders or diseases which could be included in the broad classes of disorders or diseases listed in the claims.
With regards to the preventor or treatment of cancer, for example, the state of the prior art is that cancer therapy remains highly unpredictable. There are many known (in the art) types of cancer. The various types of cancers have different causative agents, involve different cellular mechanisms, and consequently, differ in treatment protocol. Symptoms and treatment depend on the cancer type and how advanced it is (see URL: http://www.nlm.nih.gov/medlineplus/cancer.html). It is known that the challenge of cancer treatment has been to target specific therapies to pathogenetically distinct tumor types, that cancer classification has been based primarily on morphological appearance of the tumor and that tumors with similar histopathological appearance can follow significantly different clinical courses and show different responses to therapy (Golub et al., page 531). Furthermore, it is known that chemotherapy is most effective against tumors with rapidly dividing cells and that cells of solid tumors divide relatively slowly and chemotherapy is often less effective against them. It is also known in the prior art (Lala et al., page 91) that the role of NO in tumor biology remains incompletely understood with both the promotion and inhibition of NO mentioned for the treatment of tumor progression and only certain human cancers may be treated by selected NO-blocking drugs. These examples show that there are different cellular mechanisms, the unpredictability in the art and the different treatment protocols.
Also, with specific reference to cancer, Ex parte Kranz, 19 USPQ2d 1216, 1219 notes the "general unpredictability of the field [of] ...anti-cancer treatment." In re Application of Hozumi et al., 226 USPQ 353 notes the "fact that the art of cancer chemotherapy is highly unpredictable".
Hence, in the absence of a showing of correlation between all the various types of kinase-mediated diseases claimed as capable of treatment or prevention through the administration of a compound of Formula 1 or a pharmaceutically acceptable salt thereof, one of skill in the art is unable to fully predict possible results from the administration due to the unpredictability.
The amount of direction or guidance present and the presence or absence of working examples
A disclosure should contain representative examples which provide reasonable assurance to one skilled in the art that the compounds which fall within the scope of a claim will possess the alleged activity. The only direction or guidance present in the instant specification is the listing of kinase-mediated diseases Applicant considers as treatable or preventable by the administration of a compound of Formula 1 or a pharmaceutically acceptable salt thereof and evaluation results on the inhibitory activity of the title compounds (see Experimental Example 1 on pages 124 and 125 of the specification). However, the specification does not contain any evidentiary support that the administration would be able to treat or prevent the many various kinase-mediated diseases listed. Furthermore, there are no working examples to support the treatment or prevention of the instantly claimed kinase-mediated diseases. It is noted that non-patent literature citations that discuss the relationships between tyrosine protein kinases including a c-MET receptor and/or RON and some of the instantly claimed kinase-mediated diseases are also absent in the specification.
Applicant has not provided any competent evidence or disclosed tests that are highly predictive for the pharmaceutical use of the instant compounds and pharmacological activity in general is a very unpredictable area. Note that in cases involving physiological activity such as the instant case, "the scope of enablement obviously varies inversely with the degree of unpredictability of the factors involved." See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).
The level of skill in the art
The level of skill in the art is high. However, due to the unpredictability in the pharmaceutical art, it is noted that each embodiment of the invention is required to be individually assessed for physiological activity by in vitro and in vivo screening to determine which kinase-mediated diseases would benefit from this activity.
Thus, the specification fails to provide sufficient support of the broad use of the administration of a compound of Formula 1 for the treatment or prevention of the various claimed kinase-mediated diseases, as a result necessitating one of skill to perform an exhaustive search for which kinase-mediated diseases can be treated or prevented by the administration of a compound of Formula 1 or a pharmaceutically acceptable salt thereof in order to practice the claimed invention.
The quantity of experimentation needed
The quantity of experimentation needed is undue experimentation. One of skill in the art would need to determine what specific kinase-mediated diseases are benefited by the administration of a compound of Formula 1 or a pharmaceutically acceptable salt thereof.
Factors such as "sufficient working examples", "the level of skill in the art" and "predictability", etc. have been demonstrated to be sufficiently lacking in the instantly claimed formulation and method. In view of the chemical nature of the invention and the lack of working examples regarding the activity of the claimed compounds, one having ordinary skill in the art would have to undergo an undue amount of experimentation to use the invention commensurate in scope with the claims.
Genentech Inc. v. Novo Nordisk A/S (CA FC) 42 USPQ2d 1001, states that "a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion" and ”[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".
Therefore, in view of the Wands factors and In re Fisher (CCPA 1970) discussed above, to practice the claimed invention herein, a person of skill in the art would have to engage in undue experimentation to test which specific kinase-mediated diseases can be treated or prevented by the administration of a compound of Formula 1 or a pharmaceutically acceptable salt thereof.
This rejection can be overcome by amending the claims to be drawn to a method for treating specific tyrosine protein kinase-mediated diseases (e.g., specific types of cancer) wherein the kinase-mediated disease has high activity of c-MET and/or RON receptors along with providing non-patent literature citations that discuss the relationships between tyrosine protein kinases including a c-MET receptor and/or RON and the above-mentioned specific diseases.
Allowable Subject Matter
Claims 1-10 are allowed. No prior art was found.
Conclusion
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/KRISTIN A VAJDA/Primary Examiner, Art Unit 1622