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 .
This is the first action on the merits.
Claims 28-63 are pending and under consideration.
Claim Rejections - 35 USC § 112
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.
Claim 29 is 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 pre-AIA the applicant regards as the invention.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 29 recites the broad recitation gastric, and the claim also recites stomach which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), first paragraph:
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 28-63 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 written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
This is a written description rejection.
A lack of adequate written description issue arises if the knowledge and level of skill in the art would not permit one skilled in the art to immediately envisage the product claimed from the disclosed process. See, e.g., Fujikawa v. Wattanasin, 93 F.3d 1559, 1571,39 USPQ2d 1895, 1905 (Fed. Cir. 1996) (a "laundry list" disclosure of every possible moiety does not constitute a written description of every species in a genus because it would not "reasonably lead" those skilled in the art to any particular species); In re Ruschig, 379 F.2d 990, 995, 154 USPQ 118, 123 (CCPA 1967).
An applicant may also show that an invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics which provide evidence that applicant was in possession of the claimed invention, i.e., complete or partial structure, other physical and/or chemical properties, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics.
In particular, the specification as original filed fails to provide sufficient written bases for the full scope of the compounds of formula (I’) and the treatment of cancer generally, or even the scope of the cancers in claims 29 and 30. The mere fact that Applicant may have discovered a method of treating a cancer that is amplified or overexpressed with ERBB2 or mutant ERBB2 receptor kinase with some of the compounds embraced by formula (I’) is not sufficient to claim the entire genus of compounds of formula (I’) or cancers.
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure "indicates that the patentee has invented species sufficient to constitute the gen[us]."
The rejection is made under 35 USC 112 (a) (Written Description).
Claims 28-63 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 method of treatment of a patient having a cancer that is amplified or overexpressed with ERBB2 or mutant ERBB2 receptor kinase, does not reasonably provide enablement for treatment of all forms of cancer, and in particular forms of cancer that are not characterized by amplified or overexpressed ERBB2 or mutant ERBB2 receptor kinase. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims.
There are several 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”. These factors include 1) the breadth of the claims, 2) the nature of the invention, 3) the state of the art, 4) the level of one of ordinary skill, 5) the level of predictability in the art, 6) the amount of direction provided by the inventor and the existence of working examples, and 7) the quantity of experimentation needed to make or use the invention based on the content of the disclosure. In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988).
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 more recently in Liebel-Flarsheim Co. v. Medrad, Inc., 481 F.3d 1371, 82 USPQ2d 1113; Auto. Tech. Int’l, Inc. v. BMW of N. 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).
1) The breadth of the claims: The instant claims are drawn broadly to methods of treatment of patients having any type of cancer (claim 28), comprising administering a compound of a formula I’ selected from among the structurally-related alternatives of claim 1, or general treatment of patients having a more limited number of types of cancers (claim 29), or general treatment of patients having non-small cell lung cancer.
2) The nature of the invention: The invention comprises methods of pharmacologically treating cancer in general with any member of a set of recited compounds of formula I’ designed to act as irreversible covalent inhibitors of ERBB2 receptor kinase by selectively modifying the enzyme or a mutant thereof.
3) The state of the art:
According to Feldinger (Breast Cancer: Targets and Therapy 2015 147-162), the structurally-analogous quinolinyl-core compound neratinib (see structure below) is an irreversible inhibitor of ERBB2 and also has activity against EGFR (Abstract and throughout), rendering the compound a particularly attractive agent in targeting of Her2-positive breast cancer (p. 150-151) and/or NSCLCs having activating EGFR mutations (p. 154). However, patients lacking overexpression of Her2, for example those having triple-negative breast cancer (lacking Her2 overexpression or gene amplification) did not have a statistically significant improvement in pathological complete response (pCR) when treated with neratinib and chemotherapy in comparison with chemotherapy alone (p. 154).
PNG
media_image1.png
331
489
media_image1.png
Greyscale
.
Inasmuch that many cancers do not comprise overexpressed, amplified ERRB2 or mutant ERBB2 receptor kinase, the ordinary artisan at the time the instant application was effectively filed would have concluded that the disclosure does not satisfy the enablement requirement for general treatment of cancer using the recited compounds, but is only enabled for treatment of cancers comprising overexpression, amplification of ERBB2 or mutated ERBB2 receptor kinase. Further, according to Bauer (Drug Discovery Today 2015 20(9):1061-1073), potential negatives of covalent therapeutic inhibitors include risk of idiosyncratic toxicity and/or immune-mediated drug hypersensitivity and/or drug-induced toxicity (e.g. hepatotoxicity, mutagenicity, or carcinogenicity) due the presence of the hyper-reactive warheads of inhibitors of this type (p. 1065 BOX 1). These potential downsides of use of covalent inhibitors only serve to reinforce this conclusion, where attempting treatment of cancers that do not comprise overexpression, amplification of ERBB2 or mutant ERBB2 receptor kinase the would entail risks of hypersensitivity and/or toxicity without the expected advantages of covalent receptor inhibition, where little or no disease-ameliorative covalent inhibition is expected in the absence of overexpression, amplification of ERBB2 or mutant ERBB2 receptor kinase.
4) The level of one of ordinary skill: The ordinary artisan is highly skilled in the pharmaceutical development arts.
5) The level of predictability in the art: 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 statute. Here, the level of unpredictability in the art is high, because there is no record or reasonable expectation of universal cancer treatment (claim 28), or treatment of the full scope of cancers recited in claim 29 or of NSCLC using the currently-recited compounds.
6) The amount of direction provided by the inventor and the existence of working examples: Applicants provide general direction regarding dosages [0150] and administration schedules [0152]. Applicants demonstrate inhibition of growth of a model Ba/F3 ERBB2 cell line engineered to express ERBB2 kinase [0413], and observation of phosphorylated ERBB2 and phosphorylated EGFR in BT-474 (breast cancer carcinoma) cells. Applicants do not demonstrate treatment of any other cancer cell type(s), or results of any relevant model animal or cancer xenograft studies. As such, the instant specification does not have sufficient working examples to reasonably show that Applicants’ compounds can be used to generally treat all cancers (claim 28), or to treat the sub-set of all the cancers recited in claim 29, or to generally treat NSCLC (claim 30).
7) The quantity of experimentation needed to make or use the invention based on the content of the disclosure: The scope of cancers envisioned for treatment is very broad, and it is clear that all cancers, particularly cancers that do not comprise overexpression, amplification of ERBB2 or mutant ERBB2 receptor kinase, cannot be predictably treated using the genus of drugs recited in claim 1.
Taking the above factors into consideration, including the guidance provided and state of the art, it would require an undue amount of experimentation to treat cancer generally (claim 28), or even to treat the more limited set of cancers recited in claims 29 or 30, based on the current disclosure.
Genentech Inc. vs Novo Nordisk 42 USPQ 2d 1001: “A patent is not a hunting license. It is not a reward for search but compensation for its successful conclusion and patent 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.”
MPEP 2164.01(a) states, "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 1557,1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)." That conclusion is clearly justified here. Thus, undue experimentation would be required to practice Applicants' invention.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the claims at issue are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); and In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO internet Web site contains terminal disclaimer forms which may be used. Please visit http://www.uspto.gov/forms/. The filing date of the application will determine what form should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 28-63 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-44 of U.S. Patent No. 11807649. Although the conflicting claims are not identical, they are not patentably distinct from each other because the present claims are drawn to a method of treating cancer comprising administering the compounds of formula (I’) to a subject.
The claims in the ‘649 patent are drawn to compounds of formula (I’), which is the same scope as the present application. The species in claim 27 of the ‘649 patent are embraced by the present genus. Moreover, there is no patentable distinction between compounds and methods of use of said compounds.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SUSANNA MOORE whose telephone number is (571)272-9046. The examiner can normally be reached Monday - Friday, 10:00 am to 7:00 pm.
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, Jeffrey Murray can be reached on 571-272-9023. 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.
/SUSANNA MOORE/Primary Examiner, Art Unit 1624