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 .
DETAILED ACTION
The preliminary amendment filed 04/30/2024, amended claims 1-9.
Claims 1-9 are pending and examined on the merits herein.
Priority
This application claims the following priority:
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Claim Rejections - 35 USC § 112(a)-Scope of Enablement
Claims 1-3 and 6-9 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 treating the diseases recited in instant claim 3, does not reasonably provide enablement for a method of treating or preventing a necroptosis-related disease. 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.
The criteria for enablement set out in the In re Wands, MPEP 2164.01(a), considers the following factors:
Breadth of the Claims
Independent claim 1 recites a method of preventing or treating any necroptosis-related disease, comprising administering a therapeutically effective amount of apomorphine or salt thereof, and a carrier, to a subject in need thereof, wherein neither the instant specification nor the prior art provide a limiting definition of “necroptosis-related disease.”
Level of Skill in Art
The level of skill in the art is a clinician or an artisan with a PhD.
State of the Prior Art
The prior art teaches a method of treating stroke by administering apomorphine, and the prior art teaches a method of treating inflammatory bowel disease with dopamine-2 receptor agonists (see the abstract of US 3,961,060 to Fux; the abstract of Tolstanova (IDS); and the abstract of Herak-Perkovic (IDS)).
Veo (Necroptosis in Health and Disease, published 2017, PTO-892) teaches that “regulation of necroptosis has far-reaching effects in both maintaining cellular health and as a target for the treatment of diseases.” Veo teaches that “continued development of inhibitors of RIP1, RIP3, and MLKL shows promise for disease treatment. Nevertheless, further research is needed to understand when necroptosis can be used to promote health versus promoting pathogenesis” (last paragraph).
Thus, the prior art teaches that specific necroptosis-related diseases can be treated with apomorphine, and teaches that necroptosis-related diseases can be treated, but that further research is required.
The prior art is silent regarding preventing necroptosis-related diseases.
Predictability in the Art
In view of the above teachings of the prior art, while it is predictable to treat necroptosis-related diseases, such as stroke and inflammatory bowel disease, it is not predictable to prevent necroptosis-related diseases, in general.
Moreover, Cleveland Clinic (Crohn’s Disease, PTO-892) teaches that Crohn’s disease, a necroptosis-related instant disease, cannot be prevented, but that its flare-ups and symptoms can be managed (“Prevention”).
Working Examples
The instant examples, beginning on pg. 15 of the Specification, are all directed toward a method of treating colitis, and the biochemical effects of apomorphine in a cell.
Thus, the instant examples are limited to a method of treating a single disease, colitis, wherein the final sentence of the specification states, in regard to the working example, “these results indicate that APO (apomorphine) has a protective effect against DSS-induced colitis.”
Direction and Guidance
In view of what is known in the prior art regarding necroptosis-related diseases and apomorphine, the unpredictability in the art regarding the treatment of necroptosis-related disease, and the single working example, the instant specification does not provide sufficient direction or guidance as to how to use the invention as instantly claimed.
Quantity of Experimentation
In view of the innumerable diseases encompassed by the phrase “necroptosis-related disease,” the amount of experimentation required to determine which necroptosis-related diseases are treated and which necroptosis-related diseases are prevented by apomorphine would be astronomical. This amounts to invention, not development; it is an undue amount of experimentation.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-3 and 8 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by US Patent No. 3,961,060 to Fuxe (published 1976, PTO-892).
Regarding claims 1-3, Fux teaches a method of treating stroke by administering a pharmaceutical composition comprising apomorphine (abstract).
Regarding claim 8, Fuxe teaches administration by injection (Col. 3, lines 22-36; Col. 11, lines 55-Col. 12, line 3).
Further regarding claim 2, MPEP 2111.04 states, a “‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’” Id. (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)).
In the instant case, the wherein clause expresses the desired result of the positive step of administering a therapeutically effective amount of apomorphine to a patient who has suffered from a stroke (a necroptosis-related disease).
See also MPEP 2112.02, when the claim recites using an old composition or structure and the "use" is directed to a result or property of that composition or structure, then the claim is anticipated. In re May, 574 F.2d 1082, 1090, 197 USPQ 601, 607 (CCPA 1978).
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 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.
Claims 1-3 and 6-9 are rejected under 35 U.S.C. 103 as being unpatentable over US Patent No. 3,961,060 to Fuxe (published 1976, PTO-892).
Fuxe is applied to claims 1-3 and 8 as discussed above and incorporated herein.
Regarding claims 6-7, Fuxe does not explicitly teach apomorphine hydrochloride.
Fuxe teaches the active ingredient in the form of the free base or a pharmaceutically acceptable salt thereof, e.g., the hydrochloride, in association with a pharmaceutically acceptable carrier.
As such, it would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to substitute the apomorphine with apomorphine hydrochloride, to arrive at instant claim 7. One of ordinary skill in the art would have been motivated to make such a substitution because Fuxe teaches that either the free base or the hydrochloride salt of the active agent can be used.
Regarding claim 9, Fuxe does not explicitly teach an injection composition comprising apomorphine and ethanol (Col. 113, lines 15-22).
Fuxe teaches liquid preparations for oral application comprising ethanol. Fuxe teaches parenteral injections as comprising an aqueous solution of a water soluble pharmaceutically acceptable salt (Col. 13, lines 23-30).
Since Fuxe teaches ethanol as a pharmaceutically acceptable carrier for apomorphine and teaches injection compositions as comprising aqueous solutions, wherein ethanol is soluble in water, an ordinary skilled artisan would have been motivated to formulate an injection solution of apomorphine with ethanol, since it is known in the art as a carrier for apomorphine and is water soluble.
Claims 1-5 are rejected under 35 U.S.C. 103 as being unpatentable over Tolstanova (Role of Dopamine and D2 Dopamine Receptor in the Pathogenesis of Inflammatory Bowel Disease, published 2014, IDS of 09/03/2025) in view of Herak-Perovic (Effects of dopaminergic drugs on inflammatory bowel disease induced with 2,4-dinitrofluorobenzene in ALB/c mice,” published 2001, IDS of 04/30/2024) and DrugBank (Apomorphine, published 10/19/2021, PTO-892).
Tolstanova teaches a method of treating ulcerative colitis by administering a D2R agonist, such as quinpirole or cabergoline (abstract).
Regarding claims 1-5, Tolstanova differs from that of instant claim 1 in that it does not teach apomorphine.
Herak-Perkovic teaches a method of treating inflammatory bowel disease by administering the D2receptor agonist, bromocriptine (abstract).
DrugBank teaches apomorphine as a D2 dopamine agonist (pg. 1).
Regarding claims 1-5, it would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to substitute the D2 receptor agonists quinpirole or carbergoline with apomorphine, to arrive at instant claim 1. One of ordinary skill in the art would have been motivated to make such a substitution, with a reasonable expectation of success, because:
-Tolstanova teaches that administering D2 receptor agonists treats ulcerative colitis,
- Herak-Perkovic teaches inflammatory bowel diseases in general as treated with D2 receptor agonists, distinct from those taught by Tolstanova, and
- Drugbank teaches apomorphine as a D2 dopamine agonist.
As such, an ordinary skilled artisan would have been motivated to make such a substitution to predictably arrive at a method of treating inflammatory bowel disease, and specifically ulcerative colitis, since it is known in the art that D2 receptor agonists treat these diseases.
Further regarding claim 2, MPEP 2111.04 states, a “‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’” Id. (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)).
In the instant case, the wherein clause expresses the desired result of the positive step of administering a therapeutically effective amount of apomorphine to a patient who has suffered from a stroke (a necroptosis-related disease).
See also MPEP 2112.02, when the claim recites using an old composition or structure and the "use" is directed to a result or property of that composition or structure, then the claim is anticipated. In re May, 574 F.2d 1082, 1090, 197 USPQ 601, 607 (CCPA 1978)
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAUREN WELLS whose telephone number is (571)272-7316. The examiner can normally be reached M-F 7:00-4:30.
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/LAUREN WELLS/Examiner, Art Unit 1622
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