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 .
DETAIL ACTION
This office action is a response to a 371 application filed -----12/7/2023, which is a national stage application of PCT/IB2022/055275 filed 6/7/2022, which claims foreign priority to IT102021000015095 filed 6/9/2021.
As filed, claims 1-4, 10, 14, 17-19, 22, and 24-31 are pending; and claims 5-9, 11-13, 15, 16, 20, 21, and 23 are cancelled.
Election/Restrictions
Applicant's election with traverse of Group I – Claims 1-4, 10, 14, 17-19, and 30 in the reply filed on 4/9/2026 is acknowledged.
Regarding the restriction requirement, the traversal, in summary, is on the ground(s) that unity of invention does exist between Groups I-III because there is a technical relationship that involves the same special technical feature. It is this technical feature that defines the contribution which each of the groups, taken as a whole, makes over the prior art. A search of all the claims would not impose a serious burden on the Office. Accordingly, the Office has failed to meet the burden necessary in order to sustain the requirement for restriction. Applicants request that the requirement for restriction be withdrawn.
This is not found persuasive because the Examiner has demosntrated in the previous office action that claims 1-4, 10, 14, 17-19, 22, and 24-31 are not so linked as to form a single general inventive concept and lack of unity of invention. The reasons are the following:
Group I and Groups II-III do not share a common technical feature (e.g. compound of instant formula I vs. instant compound belonging to the pyrazolone class), respectively; and
the instant compound belonging to the pyrazolone class that is common between Groups II and III is not a special technical feature that defines a contribution over the prior art. See e.g. U.S. Patent Application Publication No. 2007/0196350, hereinafter Bartels (see IDS filed 10/1/2024), which teaches the instant compound belonging to the pyrazolone class.
The vastness of the claimed subject matter and the complications in understanding the claimed subject matter impose a serious burden on the search and examination of the claimed subject matter.
Regarding the election of species requirement, the Applicant made their election, which is shown below, with traverse. The traversal is on the ground(s) that the Examiner failed to provide reasons and/or examples to support any conclusion that the species are indeed patentably distinct.
This is not found persausive because instant claim 3 contains examples of patentably distinct species of the compound of instant formula (I) (e.g. aminophenazone, dipyrone, phenazone, etc.). As mentioned in the previous office action, there is no evidence that these species are obvious variant of each other. As such, the compound of instant formula (I) lacks unity of invention and an election of species requirement is appropriate.
Accordingly, the restriction and election of species requirement is still deemed proper and is therefore made FINAL.
Claims 22, 24-29, and 31 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected inventions, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 4/9/2026.
Regarding the election of species requirement, Applicant elected the species of propyphenazone for the compound of instant formula (I); and the species of macular degeneration for the instant degenerative retinal disease, which can be found in pg. 7, Table 1 and pg. 4 line 15 of the instant specification, respectively. The claims, which read on the elected species, are instant claims 1-4, 10, 14, 17-19, and 30, according to Applicant’s reply filed on 4/9/2026.
Examination will begin with the elected species. In accordance with the MPEP 803.02, if upon examination of the elected species, no prior art is found that would anticipate or render obvious the instant invention based on the elected species, the search of the Markush-type claim will be extended. If prior art is then found that anticipates or renders obvious the non-elected species, the Markush-type claim will be rejected. It should be noted that the prior art search will not be extended unnecessarily to cover all non-elected species. Should Applicant overcome the rejection by amending the claim, the amended claim will be reexamined. Id. The prior art search will be extended to the extent necessary to determine patentability of the Markush-type claim. Id. In the event prior art is found during reexamination that renders obvious or anticipates the amended Markush-type claim, the claim will be rejected and the action made final. Id.
As per MPEP 803.02, the Examiner will attempt to determine whether the entire scope of the claims is patentable. Applicants' elected species, as shown above, does not make a contribution over the prior art.
According to MPEP 803.02: should the elected species appear non-allowable, the search of the Markush-type claim will not be extended. The Markush-type claim shall be rejected and claims to the nonelected invention held withdrawn from further consideration.
While searching for prior art on the elected species, prior art was found that anticipated other species encompassed by the claims. Both prior art rejections were made below in order to advance compact prosecution.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 12/7/2023 and 3/27/2026 has been considered by the Examiner.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Claim Rejections - 35 USC § 112(a)
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 1-4, 10, 14, 17-19, and 30 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 treating a degenerative retinal disease, does not reasonably provide enablement for preventing the abovementioned 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 make and/or use the invention commensurate in scope with these claims.
As stated in the MPEP § 2164.01(a): “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’.” In In re Wands (8 USPQ2d 1400 (Fed. Cir. 1988)), the Federal Circuit established that the following factors are to be considered when determining whether a disclosure meets the enablement requirement of the first paragraph of 35 U.S.C. § 112:
The nature of the invention - is a method of treating and/or preventing a degenerative retinal disease via a compound of instant formula (I).
The state of the prior art - the pharmacological art requires the screening of potential drug candidates in vitro and in vivo to determine if the drug candidates exhibit the desired pharmacological activities.
In order to treat a disease: one would need to precisely identify what the disease is, identify what biological target is connected with the disease, demonstrate that the drug candidate in some way modulates the normal processes of the biological target, and demonstrate that a patient benefited from such modification without detrimental side effects. Typically, this process includes in vitro laboratory screening, preclinical in vivo screening, and three phases of clinical trials. Once this arduous process has been successfully completed by a drug candidate, subsequent drug candidates will benefit from the established proof of concept. The subsequent drug candidates must demonstrate a substantial correlation between their biological activity and that of the known drug candidate.
In order to prevent a disease: one would need to precisely identify those subjects likely to acquire such a disease, administer Applicant’s claimed invention, and demonstrate that the patient did not develop the disease as a result of the administration of the claim invention.
In the instant case, the prior arts failed to recognize that the compound of instant formula (I) can prevent a degenerative retinal disease.
The predictability or unpredictability of the art – the law recognizes the pharmaceutical art as an unpredictable art and requires each embodiment to be individually assessed for physiological activity. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18 24 (CCPA 1970). Accordingly, the more unpredictable an area is the more specific disclosure is necessary in order to satisfy the statute. Section 2164.02 of the MPEP provides:
"[C]orrelation” as used herein refers to the relationship between in vitro and in
vivo animal model assays and a disclosed or a claimed method of use . . . if the
art is such that a particular model is recognized as correlating to a specific
condition, then it should be accepted as correlating unless the examiner has
evidence that the model does not correlate.
In light of these remarks, the Examiner finds that one of ordinary skill in the art would agree with the court; that is, the pharmaceutical art is unpredictable. Thus, a substantial correlation is necessary for establishing the potential of new therapeutics.
The amount of direction or guidance presented – the instant specification briefly provides explanation of the current therapeutic method (e.g. anti-VEGF drug) for the treatment of the abovementioned disease. There is no direction or guidance provided that supports a use of the compound of instant formula (I) as a drug for preventing the abovementioned disease, as instantly embraced.
The amount of guidance or direction to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art. MPEP § 2164.03 (quoting In re Fisher, 427 F.2d 833, 839, 166 USPQ 18 24 (CCPA 1970)). As identified supra, the pharmaceutical art is recognized as unpredictable.
Thus, in order to support a claim for preventing the abovementioned disease, a vast amount of evidence is required because such a claim is not supported by the prior art or the instant specification.
The presence or absence of working examples - there are no working or prophetic examples in the specification that demonstrate that the instant compounds or composition thereof may prevent the abovementioned disease, as instantly embraced. The in vivo mouse model in the specification demonstrate that the instant compounds were able to protect the retina from NaIO3- induced increase in 4-HNE.
The breadth of the claims – is incommensurate in scope with the disclosure because a fair reading of the specification fails to support a finding that the compounds of instant formula (I) may prevent the abovementioned disease in a patient.
The quantity of experimentation necessary – generally speaking, the amount of experimentation to transform a molecule into medicine is vast and the success thereof is low. Recent statistics indicate that the attrition rates during drug development remain high. Schafer et al. Drug Discovery Today 2008, 13 (21/22), 913-916. The article makes clear that there are many steps necessary to promote a new molecular entity toward its clinical use, any one of which is cumbersome.
For instance, Schafer et al. discloses: "proof of concept trials have failed when the decision to enter clinical development was based on preclinical experiments using the wrong compound, the wrong experimental model, or the wrong endpoint.” It can be gleaned from this article that a plethora of experimentation is needed to identify the lead compound (i.e. one among many in a Markush-type claim), to establish which preclinical tests are predictive of clinical success, and to establish which diseases are the best to target for each lead compound.
There is generally a vast amount of experimentation to take a drug from bench to the clinic. See e.g., Horig et al. Journal of Translational Medicine 2004, 2(44) (“Successful drug development requires satisfying a matrix of domains from relevance to the disease and the drug-ability of the target through feasibility and convenience of drug delivery, demonstration of favorable benefit-risk profile in order to achieve a drug label that reflects physician and patent acceptance.") The Examiner finds that one of ordinary skill in the art would agree with the statements in these articles; that is, the amount of experimentation required to enable a pharmaceutical drug is extensive.
The level of skill in the art - the level of ordinary skill in the art may be found by inquiring into: (1) the type of problems encountered in the art; (2) prior art solutions to those problems; (3) the rapidity with which innovations are made; (4) the sophistication of the technology; and (5) the education level of active workers in the field. Custom Accessories, Inc. v. Jeffrey-Allan Industries, Inc., 807 F.2d 855, 962 (Fed. Cir. 1986). All of those factors may not be present in every case, and one or more of them may predominate. Envtl. Designs, Ltd. v. Union Oil Co., 713 F.2d 693, 696 (Fed. Cir. 1983).
Based on the typical education level of the active workers in the field of pharmaceuticals and/or medicine, as well as the high degree of sophistication required to solve problems encountered in the art, the Examiner finds that a person of ordinary skill in the art would have at least a college degree in a field related to medicine and/or the pharmaceutical art and at least four years of work experience, i.e. a masters or doctorate level scientist/clinician.
Conclusion – Claims 1-4, 10, 14, 17-19, and 30 are rejected because the Examiner finds that the Wands factors suggest a conclusion that the skilled artisan would not be able to make and use the instant invention without undue experimentation, although the level of skill for an ordinary person in the art is high. That is, due to the breadth of the claims, the unpredictability of the art, the lack of guidance or direction from the disclosure, the lack of any working examples, and the amount of experimentation needed illustrate that a person having ordinary skill in the art would not be able to prevent a degenerative retinal disease.
Claim Rejections - 35 USC § 112(b)
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.
Claims 1-4, 10, 14, 17-19, and 30 are 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claims 1 and 10, the claims recite the phrase, “A method of preventing and/or treating a degenerative retinal disease”. The term, “and”, is interpreted by the Examiner that the degenerative retinal disease is treated and prevented at the same time. Accordingly, it is unclear to the Examiner how a patient can be treated for degenerative retinal disease, which mean that the degenerative retinal disease is present, while preventing the degenerative retinal disease at the same time. With such ambiguity, the metes and bounds of this claim is unclear, which rendered the claim indefinite.
Regarding claim 3, the claim recites the following phrase
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The phrase, “mixture thereof”, pertains to a composition, and can’t be included as one of the species for the instant compound, since a compound is not a composition. With such inclusion, the metes and bounds of this claim is unclear, which rendered the claim indefinite.
Regarding claim 14, the claim recites the following phrase
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The phrase, “mixture thereof”, pertains to a composition, and can’t be included as one of the species for the instant compound, since a compound is not a composition. With such inclusion, the metes and bounds of this claim is unclear, which rendered the claim indefinite
Regarding claim 18, the phrase "preferably" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claims 2-4, these claims are dependent of claim 1, and they failed to correct the indefiniteness issue of claim 1, which rendered these claims indefinite.
Regarding claims 14, 17-19, and 30, these claims are directly or indirectly dependent of claim 10, and they failed to correct the indefiniteness issue of claim 10, which rendered these claims indefinite.
Claim Rejections - 35 USC § 102
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, 2, 4, 10, 17, 18, and 30 are rejected under 35 U.S.C. 102(a)(1)/102(a)(2) as being anticipated by U.S. Patent Application Publication No. 2017/0273949, hereinafter Hara. See IDS filed 12/17/2023.
Regarding claims 1, 2, 4, 10, 17, 18, and 30, Hara, for instance teaches a tautomer of edaravone or pharmaceutical composition thereof (with excipient) or eye drop thereof (i.e. a topical ophthalmic composition, such as an aqueous solution with ophthalmologically acceptable excipient, such as saline, etc.), wherein edaravone has the structure of
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, and its tautomer has the structure of
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, according to paragraph 0019 of Hara. Both edaravone and its tautomer can be used to treat ophthalmologic diseases caused by angiogenesis occurring in cornea, choroid or retina, such as wet age-related macular degeneration.
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Wherein: instant variable R1 is unsubstituted phenyl; instant variable R2 is H; instant variable R3 is methyl; and instant variable R4 is H.
In addition, the Examiner, according to the guidance in MPEP 2131.02(III), also finds that a person of skill in the art, reading the disclosures of Hara (as shown below), would “at once envisage” the instantly claimed arrangement or combination, which led to the abovementioned anticipation.
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(paragraph 0110)
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(paragraph 0112)
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(paragraph 0019)
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(paragraph 0110)
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(paragraph 0109)
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.
Claim 19 is rejected under 35 U.S.C. 103 as being unpatentable over Hara.
Regarding claim 19:
Determining the scope and contents of the prior art:
Hara, for instance, teaches the abovementioned process.
Ascertaining of the difference between the prior art and the claim at issue:
Hara, for instance, did not explicitly teach the concentration of edaravone and its tautomer ranging from about 0.0001% to about 5% w/v.
Finding of prima facie obviousness --- rationale and motivation:
The Examiner does not find the abovementioned concentration as result-effective variable because the Applicant fails to demonstrate this parameter to impart any unexpected or novel aspect to the instant process (i.e. no comparative example). “[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. Accordingly, this parameter is viewed as routine experimentation to optimize the instant process, and not a patentable distinction.
Claim 1-4, 10, 14, and 30 are rejected under 35 U.S.C. 103 as being unpatentable over U.S. Patent Application Publication No. 2007/0196350, hereinafter Bartels. See IDS filed 12/7/2023.
Regarding claims 1-4, 10, 14, and 30:
Determining the scope and contents of the prior art:
Bartels, for instance, teaches a method of treating or preventing an ocular condition that has genesis in inflammation, such as macular degeneration (i.e. elected species), etc. via anti-inflammatory medicament or pharmaceutical composition thereof (with a pharmaceutically acceptable excipient). Examples of the abovementioned anti-inflammatory medicament includes propyphenazone (i.e. elected species), etc.
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(paragraph 0018)
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(paragraph 0031)
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(paragraph 0059)
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(paragraph 0055)
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(paragraph 0034)
Ascertaining of the difference between the prior art and the claim at issue:
Bartels did not explicitly teach the use of propyphenazone or pharmaceutical composition thereof for treating macular degeneration in any of its examples.
Finding of prima facie obviousness --- rationale and motivation:
MPEP 2141 states, "The key to supporting any rejection under 35 U.S.C. 103 is the clear articulation of the reason(s) why the claimed invention would have been obvious. The Supreme Court in KSR noted that the analysis supporting a rejection under 35 U.S.C. 103 should be made explicit. The Court quoting In re Kahn, 441 F.3d 977, 988, 78 USPQ2d 1329, 1336 (Fed. Cir. 2006), stated that "[R]ejections on obviousness cannot be sustained by mere conclusatory statements; instead, there must be some articulated reasoning with some rational underpinning to support the legal conclusion of obviousness.’" KSR, 550 U.S. at 418, 82 USPQ2d at 1396. Exemplary rationales that may support a conclusion of obviousness include: (A) Combining prior art elements according to known methods to yield predictable results; (B) Simple substitution of one known element for another to obtain predictable results; (C) Use of known technique to improve similar devices (methods, or products) in the same way; (D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results; (E) " Obvious to try " - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success; (F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art; (G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention."
Based on the teachings of the MPEP and KSR above, by employing the rationale in (E) above, it would have been obvious for one of ordinary skill in the art to try propyphenazone from a finite number of identified anti-inflammatory medicament in the preferred embodiments of Bartels (shown above) to yield predictable results (e.g. reasonable expectation of success in treating macular degeneration).
Claim Objections
Claims 4 and 30 are objected to because of the following informalities:
Regarding claims 4 and 30, the claims recite the phrase, “myodesopsia (floaters)” , which contains typographical error.
Such typographical error can be corrected by reciting -- myodesopsia (eye floaters) --.
Appropriate correction is required.
Conclusion
Claims 1-4, 10, 14, 17-19, and 30 are rejected.
Claims 4 and 30 are objected.
Claims 22, 24-29, and 31 are withdrawn.
Claims 5-9, 11-13, 15, 16, 20, 21, and 23 are cancelled.
Telephone Inquiry
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PO-CHIH CHEN whose telephone number is (571)270-7243. The examiner can normally be reached Monday - Friday 10:00 am to 6:00 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Clinton Brooks can be reached at (571)270-7682. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/PO-CHIH CHEN/Primary Examiner, Art Unit 1621
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