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
Claims 1-10 are pending in the present application file.
Priority
The following continuity data is acknowledged in the present application file:
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Priority is granted to PCT/IB2022/055053, filed on May 30, 2022. However, foreign priority is not granted for ITALY 102021000014177, filed on May 30, 2021, as intervening prior art has been found. To perfect priority in the present application, an English translation of the foreign priority document is required.
Information Disclosure Statement
The Information Disclosure Statement filed 11/29/2023 has been acknowledged by the Examiner. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the Examiner.
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 5 and 7-8 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Present claim 1 is drawn to a method in the treatment of a pathology selected from the group consisting of lung fibrosis and heart fibrosis comprising the step of administering to a patient in need thereof istradefylline. Present claims 5 and 7-8, which are dependent on claim 1, are drawn to wherein said treatment is aimed at a human being which is affected by an autoimmune disease, COVID-19 or chronic bronchopathy.
The specification describes the conditions and limitations in similar terms without further definition.
The specification details the effect of istradefylline on a model of organ fibrosis in laboratory mice in Example 1 on pages 7-9.
The person of ordinary skill in the art would be able to extrapolate from the description and example provided in the present specification how to treat lung fibrosis or heart fibrosis in a patient which is a human being.
There are no methods or description to extrapolate the method of treatment of lung fibrosis or heart fibrosis to a patient that is also affected by any autoimmune disease, COVID-19 and/or chronic bronchopathy.
The Applicant is reminded of the written description guidelines set out by the USPTO in MPEP 2163:
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 (see i)(A), above), reduction to drawings (see i)(B), above), 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 i)(C), above). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
While the genus is of a method of treatment for lung fibrosis or heart fibrosis is described by the present specification, the description of treatment of lung fibrosis or heart fibrosis is not sufficiently detailed to show that the Applicant was in possession of the full scope of the claimed invention at the time of filing.
Namely, that the genus described above, while not being indefinite, is not sufficiently detailed in order to stand on its own as being adequately described. Therefore, the “representative number of species” standard is used to determine whether the claims are adequately described.
MPEP 2163 goes on to describe what a "representative number of species" is:
What constitutes a "representative number" is an inverse function of the skill and knowledge in the art. Satisfactory disclosure of a "representative number" depends on whether one of skill in the art would recognize that the applicant was in possession of the necessary common attributes or features of the elements possessed by the members of the genus in view of the species disclosed. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See, e.g., Eli Lilly. Description of a representative number of species does not require the description to be of such specificity that it would provide individual support for each species that the genus embraces. For example, in the molecular biology arts, if an applicant disclosed an amino acid sequence, it would be unnecessary to provide an explicit disclosure of nucleic acid sequences that encoded the amino acid sequence. Since the genetic code is widely known, a disclosure of an amino acid sequence would provide sufficient information such that one would accept that an applicant was in possession of the full genus of nucleic acids encoding a given amino acid sequence, but not necessarily any particular species. Cf. In re Bell, 991 F.2d 781, 785, 26 USPQ2d 1529, 1532 (Fed. Cir. 1993) and In re Baird, 16 F.3d 380, 382, 29 USPQ2d 1550, 1552 (Fed. Cir. 1994). If a representative number of adequately described species are not disclosed for a genus, the claim to that genus must be rejected as lacking adequate written description under 35 U.S.C. 112, para. 1.
The species described in the specification do not cover the entire genus such that it is a representative sample of the genus as the species are close together in structure and only describe an extremely small portion of the claimed genus.
Therefore, the claims lack written description and are properly rejected under 35 U.S.C. 112(a).
Claim Rejections - 35 USC § 103
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 1-10 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang (Zhang, Jin, et al. "Adenosine A2a receptor blockade diminishes Wnt/β-Catenin signaling in a murine model of bleomycin-induced dermal fibrosis." The American journal of pathology 187.9 (2017): 1935-1944.), in view of Tokano (Tokano, Mieko, et al. "Istradefylline, an adenosine A2a receptor antagonist, ameliorates neutrophilic airway inflammation and psoriasis in mice." Clinical and Experimental Neuroimmunology 12.4 (2021): 268-275.).
Determining the scope and contents of the prior art. (See MPEP § 2141.01)
Zhang discloses ”the A2aR antagonist istradefylline (KW6002)inhibits the Wnt/β-catenin signaling pathway in vivo, which contributes to preventing bleomycin-induced dermal fibrosis. The use of KW6002, which improves motor function in animal models of Parkinson disease and in patients with Parkinson disease, has been approved in Japan as the first A2aR selective antagonist for clinical application. Our results provide evidence supporting off-label use of this drug and represents a potential novel therapeutic modality for the treatment and prevention of dermal fibrosis.” See page 1943, left column, last paragraph to page 1943, right column, first paragraph. See instant claim 3.
Zhang discloses where “activation of the WNT/β-catenin pathway is often a general feature of fibrotic diseases. Tissue samples from humans with fibrotic diseases, such as systemic sclerosis, idiopathic pulmonary fibrosis, and liver cirrhosis, showed enhanced expression of WNT proteins and decreased expression of Dickkopf-1, a secreted antagonist of WNT/β-catenin signaling.” See page 1941, right column, first paragraph.
Zhang discloses that A2aR blockade prevented fibroblast/myofibroblast transition, as reflected by α-SMA accumulation, in vivo. See page 1942, right column, penultimate paragraph.
Zhang discloses “male Tcf/Lef:H2B-GFP mice age 13 weeks (25 to 30 g) in this murine model of scleroderma were treated with the A2aR antagonist KW6002 (10 mg/kg once per day i.p., administered in vehicle consisting of 8% Tween 80 in saline to a total injection volume of 10 mL/kg) or vehicle alone”. See page 1936, right column, penultimate paragraph. See instant claims 9-10.
Ascertainment of the differences between the prior art and the claims. (See MPEP § 2141.02)
Zhang does not disclose where lung fibrosis or heart fibrosis is treated by administration of istradefylline.
Zhang does not disclose where treatment is aimed at a human being, or further where said human being is affected by an autoimmune disease, COVID-19 or chronic bronchopathy. See instant claims 5 and 7-8.
Finding of prima facie obviousness --- rationale and motivation (See
MPEP § 2142-2143)
Tokano discloses the following on page 273, left column:
“Our studies show that istradefylline treatment suppressed IL-17-dependent neutrophilic airway inflammation in DO11.10 mice. Similarly, ARL67156 and AMP-CP, which inhibit the production of adenosine, suppressed IL-17-dependent neutrophilic airway inflammation, which corroborates our previous findings. Furthermore, the modulation of signaling through A2aR might ameliorate autoimmune diseases, including allergy and infections. The latter might include disseminated intravascular coagulation or acute respiratory distress syndrome in SARS-CoV-2 disease (coronavirus disease 2019 [COVID-19]), which is reportedly associated with neutrophil extracellular traps. In recent previous studies, patients with severe COVID-19 showed the aberrant activation of neutrophils and Th17 promotion, and IL-17 can serve as a biomarker of the severity of COVID-19. Indeed, autopsy samples from the lungs of COVID-19 patients showed neutrophil infiltration in pulmonary capillaries, and the peripheral blood of patients showed an increased frequency of Th17 cells. Accordingly, it is conceivable that istradefylline treatment might suppress IL-17 secretion and neutrophilic airway inflammation in COVID-19.”
Zhang discloses where istradefylline has efficacy as a treatment for dermal fibrosis. Zhang provides evidence supporting off-label use of istradefylline drug and represents a potential novel therapeutic modality for the treatment and prevention of dermal fibrosis
Zhang discloses ”the A2aR antagonist istradefylline (KW6002)inhibits the Wnt/β-catenin signaling pathway in vivo and where the WNT/β-catenin pathway is often a general feature of fibrotic diseases. Zhang also discloses that A2aR blockade prevented fibroblast/myofibroblast transition. Zhang further provides tissue samples from humans with fibrotic diseases, such as systemic sclerosis, idiopathic pulmonary fibrosis, and liver cirrhosis, showed enhanced expression of WNT proteins.
Tokano discloses where istradefylline treatment suppressed IL-17-dependent neutrophilic airway inflammation in mice and the modulation of signaling through A2aR might ameliorate autoimmune diseases, including allergy, infections and disseminated intravascular coagulation or acute respiratory distress syndrome in SARS-CoV-2 disease (coronavirus disease 2019 [COVID-19]).
It would have been prima facie obvious for one of ordinary skill in the art to combine the disclosures of Zhang and Tokano, in an application for the treatment of lung fibrosis. Zhang discloses where istradefylline has efficacy in the treatment of another type of fibrosis and both Zhang and Tokano report the effects of istradefylline on pulmonary disorders and symptoms thereof. As istradefylline is known as a selective A2aR antagonist, which is associated with fibroblast/myofibroblast activation, as well as an inhibitor of the Wnt/β-catenin signaling pathway, associated with systemic fibrosis and idiopathic pulmonary fibrosis, there would be a reasonable expectation of success towards the effective treatment of lung fibrosis and heart fibrosis.
Regarding claims 5 and 7-8, Tokano discloses where the modulation of signaling through A2aR might ameliorate autoimmune diseases, including allergy and infections. The latter might include disseminated intravascular coagulation or acute respiratory distress syndrome in SARS-CoV-2 disease (coronavirus disease 2019 [COVID-19]), which is reportedly associated with neutrophil extracellular traps. Tokano also discloses where it is conceivable that istradefylline treatment might suppress IL-17 secretion and neutrophilic airway inflammation in COVID-19.
Zhang and Tokano disclose a method for the treatment of lung fibrosis and heart fibrosis comprising administration of istradefylline .Tokano further discloses istradefylline as potentially therapeutic in subjects having COVID-19, autoimmune diseases and to reduce airway inflammation. One of ordinary skill in the art would have a reasonable expectation of success towards treating a subject for lung fibrosis or heart fibrosis, said subject also having the instant claimed conditions with istradefylline.
Regarding claim 9, Zhang discloses where istradefylline is administered to mice at a dosage of 10 mg/kg once per day. "[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). See MPEP 2144.05,II.A. It would have been obvious for one of ordinary skill in the art to adjust the appropriate dosage of istradefylline during routine optimization to achieve the desired therapeutic effect.
Conclusion
Claims 1-10 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to QUINCY A MCKOY whose telephone number is (703)756-4598. The examiner can normally be reached Monday - Thursday 8:00 - 6:00.
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/QUINCY A. MCKOY/
Patent Examiner, Art Unit 1626
/KAMAL A SAEED/Primary Examiner, Art Unit 1626