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 .
Priority
Acknowledgment is made of applicant's claim for foreign priority under 35 U.S.C. 119(a)-(d) by application nos. EP19187247.2 and EP20174154.3 filed in the European Patent Office on July 19, 2019 and May 12, 2020, respectively, which papers have been placed of record in the file.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on July 14, 2022, July 29, 2022, and August 16, 2023 were in compliance with the provisions of 37 CFR 1.97 and 37 CFR 1.98. The IDS documents were considered. A signed copy of each form 1449 is enclosed herewith.
Status of Claims
Claims 17-36 are pending and under consideration in the instant application.
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.
5. Claims 17-36 are rejected under 35 U.S.C. 112, first paragraph, 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 make and use the invention commensurate in scope with these claims. Specifically, while there is enablement for the treatment of kidney injuries, there is no enablement for the prevention of kidney injuries in the instant specification.
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. These factors include, but are not limited to: (a) breadth of the claims; (b) nature of the invention; (c) state of the prior art; (d) level of one of ordinary skill in the art; (e) level of predictability in the art; (f) amount of direction provided by the inventor; (g) existence of working examples; and (h) quantity of experimentation needed to make or use the invention based on the content of the disclosure. (See Ex parte Forman 230 USPQ 546 (Bd. Pat. App. & Inter. 1986) and In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988).
The above factors, regarding the present invention, are summarized as follows:
(a) Breadth of the claims - The breadth of the claims is drawn to treatment and prevention of kidney injuries.
(b) Nature of the invention - The nature of the invention is therefore drawn to the pharmaceutical art.
(c,e) State of the prior art and predictability in the art - 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 or preventative regimen on its face.
The prophylaxis or prevention actually means to anticipate or counter in advanced, 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 and compositions can be administered in order to have the "preventive" effect. How would one show a correlation that the diseases of the instant claims are prevented by the compounds of the invention, or that the subject would not have contracted the disease either way? How does one prevent the initial onset of the kidney injuries?
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 preventative regimen on its face.
(d) Level of one of ordinary skill in the art - The artisans using applicant’s method would be a collaborative team of synthetic chemists and/or health practitioners, possessing commensurate degree level and/or skill in the art, as well as several years of professional experience.
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 or in vivo screening to determine which compounds exhibit the desired pharmacological activity and which diseases would benefit from this activity.
(f-g) Amount of direction provided by the inventor and existence of working examples - The only direction or guidance present in the instant specification is the listing of diseases applicant considers as preventable by admiration of the claimed compounds.
There are absolutely no working examples present for the prevention of kidney injuries.
Test assays and procedures are not provided in the specification and the disclosure does not provide how the in vitro data correlates to the prevention of polycystic kidney disease.
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).
Furthermore, there is no evidence of record, which would enable the skilled artisan in the identification of the people who have the potential of becoming afflicted with the numerous diseases/disorders or conditions claimed herein. That a single compound can be used to prevent the conditions embraced by the claim is an incredible finding for which Applicant has not provided supporting evidence. Applicant has not provided any competent evidence or disclosed tests that are highly predictive for the pharmaceutical use for preventing any or all of the diseases/disorders or conditions by administering the instant claimed compound.
(h) Quantity of experimentation needed to make or use the invention based on the content of the disclosure - The quantity of experimentation needed is undue experimentation. One of skill in the art would need to determine what diseases, disorders, or conditions out of all diseases, disorders, or conditions would be benefited and would furthermore then have to determine which of the claimed compounds in the instant invention would provide prevention of polycystic kidney disease.
A person having ordinary skill in the art at the time the invention was made would be faced with an undue amount of experimentation to use the pharmaceutical compositions for the full scope of the claimed intended uses.
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)}.
The specification fails to provide sufficient support of the broad use of the methods of administering compounds of the instant claims for the prevention of polycystic kidney disease, as a result necessitating one of skill to perform an exhaustive search for which diseases can be treated or prevented by what compounds of the invention in order to practice the claimed invention.
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 “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”.
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 diseases can be treated by the compounds encompassed in the instant claims, with no assurance of success.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103(a) are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
6. Claim(s) 17-36 is/are rejected under 35 U.S.C. 103 as being unpatentable over Dürrenberger et. al., WO 2017068089 A2, publ. 4/27/2017, cited in an IDS in view of Ueda et al., Curr. Med. Chem., 2017, 24(14), 1417-52.
Dürrenberger teaches ferroportin inhibitors for the treatment of iron metabolism disorders (title & abstract; p. 1, lines 4-7) related to or caused by increased iron levels or iron overload. Dürrenberger teaches compounds of formula (I), shown below, as ferroportin inhibitors (p. 7, line 4-p. 8, line 17):
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. Dürrenberger teaches the compound of the instant claims as a particularly preferred ferroportin inhibitor (p. 40, line 25-p. 51, see compound 127):
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; in particular, this compound is exemplified within an assay of 11 ferroportin inhibitors (p. 109, see Table 5), encompassed by instant claims 28-35). In other embodiments, Dürrenberger includes a specific group of diseases associated with increased iron levels to be treated (p. 67, lines 22-26; p. 409, claims 38 & 39). Treatment is taught to encompass treatment of disease symptoms and states (p. 69, lines 16-23). Dürrenberger teaches administration of a ferroportin inhibitor as described above in various pharmaceutical compositions including oral dosage forms (p. 70, lines 7-16). Dürrenberger teaches compound 127 as the 3HCl salt (p. 266, Ex. 127):
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. Administration (instant claims 24-27) of a ferroportin inhibitor compound from one to four times per day is taught, at a dose from 0.001-500 mg/kg of body weight, but that the dose can be modified depending on the age, weight, condition of the patient, or severity of the condition (p. 70, lines 17-20). Administration to a human patient with a disease related to increased iron levels is taught (p. 70, lines 25-31). Administration of compound 127 at doses of 1 mg/kg, 3 mg/kg, 10 mg/kg, 30 mg/kg, or 100 mg/kg is exemplified (p. 112, Table 7). Dürrenberger teaches combination therapy (instant claim 26), wherein a ferroportin inhibitor compound is administered in combination with at least one additional therapeutic, at fixed or free doses (p. 69, lines 24-44); additional therapeutic agents are taught to include active agents for the treatment of iron overload (p. 410, claim 46).
Dürrenberger does not specifically teach kidney injury. Ueda et al. cures this deficiency. Ueda et al. teaches kidney injuries induced by catalytic free iron of instant claim 18 (pg. 1417 left column), AKI of instant claims 19-22 (pg. 1434, col. 2 sec 9 and throughout reference), decrease of H-ferritin levels of instant claim 23, (pg. 1435, right col. first paragraph).
It would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claims to have arrived at the instantly claimed method of treating kidney injury in a human patient in need thereof comprising administering a compound shown below, or a pharmaceutical salt thereof, in view of the teachings of Dürrenberger:
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. Dürrenberger teaches treatment of diseases associated with or related to iron overload or excess iron levels, by administering an effective dose of a ferroportin inhibitor, wherein the compound of the instantly claimed method is exemplified. Dürrenberger further teaches treatment of a human patient by oral administration of a ferroportin inhibitor compound in dosage forms such as capsules, as well as administration from one to four times daily. Ueda et al. teaches the treatment of kidney injuries related to or caused by increased iron levels or iron overload. As such, one of ordinary skill in the art would have been motivated to have treated kidney injury in a human patient comprising administering the compound of the instant claims, and have had a reasonable expectation of success.
Dürrenberger teaches administration of a ferroportin inhibitor at a dose from 0.001-500 mg/kg of body weight, as well as that the dose can be modified depending on the age, weight, condition of the patient, or severity of the condition. Additionally, administration of the compound of the instant claims at doses of 1 mg/kg, 3 mg/kg, 10 mg/kg, 30 mg/kg, and/or 100 mg/kg is exemplified. Therefore, it would have been prima facie obvious to one of ordinary skill in the art to have administered the compound at the daily doses recited by claims 27, 29, 30, and 32, wherein the compound is administered at a daily dose of 5 mg, 15 mg, 30 mg, 60 mg, 120 mg, or 240 mg; and administration of the compound at a daily dose of 30 mg or 60 mg to patients with a body weight of ≥ 50 kg and ≤ 100 kg as recited by instant claims 30 and 32 by routine experimentation, in the absence of evidence indicating criticality of these doses. See MPEP 2144.05(I): Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Regarding the limitation of claims 35-36, Dürrenberger teaches combination therapy wherein the ferroportin inhibitor is administered in combination with another active agent, including active agents for the treatment of iron overload. Since kidney injury is included as an iron overload disease, it would have been prima facie obvious to have arrived at the limitation of claims 35-36, wherein the ferroportin inhibitor compound of the instant claims is administered in combination with another kidney injury medicament.
Conclusion
7. No claims are allowed.
8. Any inquiry concerning this communication or earlier communications from the examiner should be directed to Samantha Shterengarts whose telephone number is (571)270-5316. The examiner can normally be reached on Monday thru Thursday 9-6pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Mr. 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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/SAMANTHA L SHTERENGARTS/Primary Examiner, Art Unit 1623
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