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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after allowance or after an Office action under Ex Parte Quayle, 25 USPQ 74, 453 O.G. 213 (Comm'r Pat. 1935). Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, prosecution in this application has been reopened pursuant to 37 CFR 1.114. Applicant's submission filed on 04/14/2026 has been entered.
Priority
Acknowledgment is made of applicant’s claim for priority in parent Application No. 62/469,133, filed on 3/9/2017.
Information Disclosure Statement
The information disclosure statement filed 04/14/2026 fails to comply with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609 because reference numbers 6 and 16 have not been provided. It has been placed in the application file, but the information referred to therein has not been considered as to the merits. Applicant is advised that the date of any re-submission of any item of information contained in this information disclosure statement or the submission of any missing element(s) will be the date of submission for purposes of determining compliance with the requirements based on the time of filing the statement, including all certification requirements for statements under 37 CFR 1.97(e). See MPEP § 609.05(a).
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 1-2, 7, 9-14, 16-17 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 the method of instant claim 1 wherein the TKI is cabozantinib, does not reasonably provide enablement for the method of instant claim 1 wherein the TKI is lapatinib, sunitinib, sorafenib, erlotinib, gefitinib, axitinib, imatinib, nilotinib, dasatinib, ruxolitinib, bosutinib or valatinib. 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.
To be enabling, the specification of the patent 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 (Fed. Cir. 1993). Explaining what is meant by “undue experimentation,” the Federal Circuit has stated:
The test is not merely quantitative, since a considerable amount of experimentation is permissible, if it is merely, or if the specification in question provides a reasonable amount of guidance with respect to the direction in which the experimentation should proceed to enable the determination of how to practice a desired embodiment of the claimed invention. PPG v. Guardian, 75 F.3d 1558, 1564 (Fed. Cir. 1996). [1]
The factors that may be considered in determining whether a disclosure would require undue experimentation are set forth by In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 where the court set forth the eight factors to consider when assessing if a disclosure would have required undue experimentation. Citing Ex parte Forman, 230 USPQ 546 (BdApls 1986) at 547 the court recited eight factors:
1) the quantity of experimentation necessary,
2) the amount of direction or guidance provided,
3) the presence or absence of working examples,
4) the nature of the invention,
5) the state of the prior art,
6) the relative skill of those in the art,
7) the predictability of the art, and
8) the breadth of the claims.
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. In re Fisher, 57 CCPA 1099, 1108, 427 F.2d 833, 839, 166 USPQ 18, 24 (1970). Keeping that in mind, the Wands factors are relevant to the instant fact situation for the following reasons:
1. The nature of the invention, state and predictability of the art, and relative
skill level
The invention relates to a method of treating diarrhea in a cancer patient, wherein this associated with tyrosine kinase inhibitor (TKI) therapy, the method comprising administering to the cancer patient concurrently with the TKI therapy,crofelemerthe diarrhea, wherein theTKI therapy comprises administration of a TKI is selected from lapatinib, sunitinib, sorafenib, erlotinib, gefitinib, axitinib, imatinib, nilotinib, dasatinib, cabozantinib, ruxolitinib, bosutinib and valatinib”. The relative skill of those in the art is high, that of an MD or PHD. That factor is outweighed, however, by the unpredictable nature of the art. As illustrative of the state of the art, the examiner cites the fact the arguments submitted by the applicants 11/07/2025 were persuasive in that there is not a reasonable expectation of success for the successful treatment with Crofelemer based on a common mechanism of TKI drugs because as show in the IDS publication Van Sebille (VAN SEBILLE, Y et al., "Dacomitinib-induced diarrhea: targeting chloride secretion with crofelemer", Accepted Article, doi: 10. 1002/ilc.3 1048, International Journal of Cancer, 2018, pages 1-31.), “Crofelemer worsened dacomitinib-induced diarrhea, suggesting that antisecretory drug therapy may be ineffective in this setting”(abstract). Thus there is no reasonable expectation that diarrhea caused by each of these other TKI drugs would improve by administering Crofelemer and thus no reasonable expectation and no predictability that the claims are enabled. The amount of guidance or direction needed to enable the invention is inversely related to the degree of predictability in the art. In re Fisher, 839, 166 USPQ 24. Thus, although a single embodiment may provide broad enablement in cases involving predictable factors, such as mechanical or electrical elements, in cases involving unpredictable factors, such as most chemical reactions and physiological activity, more teaching or guidance is required. In re Fisher, 427 F.2d 839, 166 USPQ 24; Ex Parte Hitzeman, 9 USPQ 2d 1823.
2. The breadth of the claims
The claims are thus very broad insofar as they recite the treating diarrhea in a cancer patient, wherein this associated with tyrosine kinase inhibitor (TKI) therapy, the method comprising administering to the cancer patient concurrently with the TKI therapy,crofelemerthe diarrhea, wherein theTKI therapy comprises administration of a TKI is selected from lapatinib, sunitinib, sorafenib, erlotinib, gefitinib, axitinib, imatinib, nilotinib, dasatinib, cabozantinib, ruxolitinib, bosutinib and valatinib”. While such “treatment” might be possible for cabozantinib as demonstrated in the IDS reference Greene et al. as a practical matter it is nearly impossible to reasonably predict which of the TKI inhibitors would be enabled for this method without undue experimentation.
3. The amount of direction or guidance provided and the presence or absence of working examples
The specification provides no direction or guidance for the use of all compounds of instant claim 1. No reasonably specific guidance is provided concerning useful therapeutic protocols for all of the disclosed compound’s treatment combinations. No working examples demonstrating enablement of instant claim 1 with lapatinib, sunitinib, sorafenib, erlotinib, gefitinib, axitinib, imatinib, nilotinib, dasatinib, cabozantinib, ruxolitinib, bosutinib or valatinib have been provided in the instant specification.
4. The quantity of experimentation necessary
Because of the known unpredictability of the art, and in the absence of experimental evidence, no one skilled in the art would accept the assertion that every instantly claimed method of treatment in claim 1 could be predictably used for the treatment of diarrhea caused by lapatinib, sunitinib, sorafenib, erlotinib, gefitinib, axitinib, imatinib, nilotinib, dasatinib, ruxolitinib, bosutinib or valatinib as inferred by the claims and contemplated by the specification. Accordingly, the instant claims do not comply with the enablement requirement of §112, since to practice the invention claimed in the patent a person of ordinary skill in the art would have to engage in undue experimentation, with no assurance of success. Genetech, 108 F.3d at 1366 states that “a patent is not a hunting Iicense. 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.''
[1] As pointed out by the court in In re Angstadt, 537 F.2d 498 at 504 (CCPA 1976), the key word is “undue”, not “experimentation”.
Allowable Subject Matter
Claims 18 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
Claims 1-2, 7, 9-14, 16-17 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALISON AZAR HASTINGS whose telephone number is (703)756-4584. The examiner can normally be reached Mon-Thurs 7:30am-5pm EST Friday 7:30-4pm EST (every other Friday off).
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/A.A.H./ Examiner, Art Unit 1627
/Kortney L. Klinkel/ Supervisory Patent Examiner, Art Unit 1627
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