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 .
Status of the Claims
Claims 1-20 are pending and examined.
Claim of Foreign Priority
No claim of foreign priority has been presented.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
NOTE: The examiner did not apply duplicative references or teachings in rejections below. For example, the DP rejections include patents that also qualify as prior art. They are not all presently applied.
The examiner cites Perkovic et al., “Association of Lipid Peroxidation Product 4-Hydroxynonenal with Post-Traumatic Stress Disorder,” Biomolecules. 2021 Sep 15;11(9):1365, for supporting the enablement of PTSD.
Claim Rejections – 35 USC § 112 (Scope of Enablement)
The following is a quotation of the first paragraph of 35 U.S.C. 112(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 1-20 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 mitigation of symptoms relating to SLS and PTSD (in view of Perkovic cited above), does not reasonably provide enablement for treating each of the claimed conditions, including OCD, bipolar disorder, severe PMS, depression, bipolar disorder, any neurological symptom, neurodegeneration, seizures, myopia, and photophobia. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to treat a subject population having a claimed condition with any analog or variant. Treatment of some neurodegenerative conditions are known in the art, as set forth, e.g., in the cited prior art and such treatment for PTSD, SLS, and others.
Applicant can obviate this rejection by showing that the mechanism of action taught to be effectuated by the claimed agent will treat claimed conditions. The state of the art can be used to established this.
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 (1988), factors to be considered in determining whether a disclosure meets the enablement requirement of 35 U.S.C. 112, first paragraph, have need described. They are:
1. The nature of the invention
2. The state of the prior art
3. The predictability or lack thereof in the art
4. The amount of direction or guidance present
5. The presence or absence of working examples
6. The breadth of the claims
7. The quantity of experimentation needed, and
8. The level of skill in the art
The Nature of the Invention
The instant claims are drawn to treating OCD, bipolar disorder, severe PMS, depression, bipolar disorder, any neurological symptom, neurodegeneration, seizures, myopia, and photophobia. . Treatment of these conditions once a subject has been identified is broad.
The State of the Prior Art and the Predictability or lack thereof in the art
The state of the prior art is that the pharmacological art involves screening invitro and in vivo to determine which compounds exhibit the desired pharmacological activities (i.e. what compounds can treat which specific diseases/conditions 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 and treat one of ordinary skill in the art from accepting any therapeutic regimen on its face.
The instantly claimed invention is highly unpredictable as discussed below: It is noted that the pharmaceutical art is unpredictable, requiring each embodiment to be individually assessed for physiological activity. In re Fisher, 427 F.2d 833, 166 USPQ 18 (CCPA 1970) indicates that the more unpredictable an area is, the more specific enablement is necessary in order to satisfy the statute. In the instant case, the instantly claimed invention is highly unpredictable since one skilled in the art would recognize the distinct nature of including OCD, severe PMS, depression, bipolar disorder, any neurological symptom, neurodegeneration, seizures, myopia, and photophobia. .
The Amount of Direction / Guidance Present and the Presence or Absence of Working Examples
The Example in the Specification begins on page 78. The examples focus on patients with SLS and biomarkers relating thereto, including plasma fatty alcohols, alkyl glycerols, white matter disease, brain disease, spasticity, TEWL that is considered abnormal, and a measure of ichthyosis. Factors also evaluated include a qualify of life survey, perimacular crystalline inclusions. See pages 84-85.
There are no other conditions described. As such, we must fill in the gaps with the state of the art and the knowledge already in the art. The examiner was not able to identify state of the art references providing for a reasonable basis to believe that the claimed compound can treat the breadth of the claimed conditions. Applicant can provide a showing in an effort to obviate this rejection.
The level of the skill in the art
The level of skill in the art is high. However, due to the unpredictability in the pharmaceutical art as described above, it is noted that each embodiment of the invention is required to be individually assessed for physiological activity by in vitro and in vivo screening to determine whether the compound exhibits the desired pharmacological activity. 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 Fishcher, 427 F.2d 839, 166 USPQ 24; Ex Parte Hitzeman, 9 USPQ 2d 1823.
The quantity of experimentation needed
The quantity of experimentation needed is undue experimentation. One of skill in the art would need to definitively determine the specific population of individuals who would need to be treated and would furthermore have to determine which of the claimed compounds would provide for the treatment of OCD, severe PMS, depression, bipolar disorder, any neurological symptom, neurodegeneration, seizures, myopia, and photophobia would require undue experimentation to both develop an animal model which would reasonably correlate with all forms of neurodegenerative diseases and also to identify the portion of the population in which the instantly claimed compounds would need to necessarily be administered.
The cited prior art teaches treatment of specific conditions with the claimed agent by inhibiting MDA and HNE (i.e., toxic aldehydes). There is no reason to believe that this can treated each claimed condition including OCD, severe PMS, depression, bipolar disorder, any neurological symptom, neurodegeneration, seizures, myopia, and photophobia. The sole conditions evaluated in the examples in the instant Specification is Sjogren-Larsson syndrome.
Thus, factors such as “sufficient working examples”, “the level of skill in the art” and “predictability”, etc. have been demonstrated to be sufficiently lacking in the instantly claimed methods. In view of the breadth of the claim, the chemical nature of the invention, and the lack of working examples regarding the activity of the claimed compounds, one having ordinary skill in the art would have to undergo an undue amount of experimentation to use the invention commensurate in scope with the claims.
The court in Genentech Inc. v. Novo Nordisk A/S (CAFC) 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 “[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.”
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 with the claimed compound encompassed in the instant claims, with no assurance of success.
Claim Rejections - 35 USC § 102/103
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.
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.
Claims 1-20 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by, and in the alternative, obvious under 35 U.S.C. 103 as being unpatentable over Machatha et al., (US20200062712).
Machatha teaches the claimed compound for treating conditions including neurological conditions, skin conditions, ocular conditions, and others. It acts to scavenge toxic aldehydes such as MDA and HNE. See Abstract. Metabolic and inflammatory processes in cells generate toxic aldehydes, such as malondialdehyde (MDA) and 4-hydroxy-2-nonenal (HNE or 4-HNE). See par. 2. Machatha teaches treating and reducing conditions in which aldehyde toxicity is part of the pathogenesis. See par. 18. The amino and carbinol functionality are thought to treat and scavenge aldehydes. Conditions that can be treated include Sjogren-Larsson Syndrome and /or associated ichthyosis, neurological and motor effects of SLS, PD, AD, MS, ALS, and others. See par. 40. Compounds can be administered orally, including in the form of a capsule or tablet with excipients. See par.’s 48 and 49. Further, dosages can include from 0.1 to 10 mg/kg and discrete amounts of 100 mg, 250 mg, and 500 mg, among others. See par. 51.
Machatha discloses embodiments in which macular degeneration is treated with a claimed compound. See par.’s 144 and 145.
While the specific result of inhibiting each claimed aldehyde is not taught by the prior art, absent evidence to the contrary, when the claimed agent is administered orally and/or systemically to a same subject population, the claimed result would occur. There is a specific motivation to administer the claimed agent to a claimed subject with SLS or ichthyosis, neurological condition, cognitive delay, spasticity, and other claims conditions. See par. 136.
It would have been prima facie obvious to a person having ordinary skill in the art prior to the filing of the instant application to arrive at the claimed methods in view of Machatha, Li, and Shapiro. One would be motivated to do so because the claimed compound is taught to treat conditions in which toxic aldehydes are implicated in the pathogenesis. The claimed compound is taught to scavenge toxic aldehydes including 4-HNE and MDA. The primary amine is taught to scavenge MDA and 4-HNE. See Table 1, compound 1. It is thought that the claimed compound reacts with MDA and HNE, among other toxic aldehydes, to reduce or eliminate their ability to react with proteins, lipids, carbohydrates, and DNA. See par. 121. They form a closed structure thereby trapping the aldehydes. Such action will treat conditions including macular degeneration, SLS, ichthyosis, and numerous neurodegenerative and neurological conditions. As such, administration of the claimed compound at a dosage that is taught to be administered systemically and inhibit the activity of HNE and MDA has a reasonable and predictable expectation of success. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985); and 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).
Claims 1-20 are rejected under 35 U.S.C. 103 as being unpatentable over Machatha et al., (US20200062712), in view of Li et al., “Oxidative Stress and 4-hydroxy-2-nonenal (4-HNE): Implications in the Pathogenesis and Treatment of Aging-related Diseases,” Journal of Immunology Research Volume 2022 (received May 2021), and in view of Shapiro et al., “Ongoing Trials in AMD,” Retina Today July/August 2013.
Machatha teaches the claimed compound for treating conditions including neurological conditions, skin conditions, ocular conditions, and others. It acts to scavenge toxic aldehydes such as MDA and HNE. See Abstract. Metabolic and inflammatory processes in cells generate toxic aldehydes, such as malondialdehyde (MDA) and 4-hydroxy-2-nonenal (HNE or 4-HNE). See par. 2. Machatha teaches treating and reducing conditions in which aldehyde toxicity is part of the pathogenesis. See par. 18. The amino and carbinol functionality are thought to treat and scavenge aldehydes. Conditions that can be treated include Sjogren-Larsson Syndrome and /or associated ichthyosis, neurological and motor effects of SLS, PD, AD, MS, ALS, and others. See par. 40. Compounds can be administered orally, including in the form of a capsule or tablet with excipients. See par.’s 48 and 49. Further, dosages can include from 0.1 to 10 mg/kg and discrete amounts of 100 mg, 250 mg, and 500 mg, among others. See par. 51.
Machatha discloses embodiments in which macular degeneration is treated with a claimed compound. See par.’s 144 and 145.
While the specific result of inhibiting each claimed aldehyde is not taught by the prior art, absent evidence to the contrary, when the claimed agent is administered orally and/or systemically to a same subject population, the claimed result would occur. There is a specific motivation to administer the claimed agent to a claimed subject with SLS or ichthyosis, neurological condition, cognitive delay, spasticity, and other claims conditions. See par. 136.
Li teaches toxic aldehydes including 4-HNE and MDA play an important role in the development of aging related diseases. “4-HNE can activate various molecules, such as NF-κB and NOX4, to induce RPE apoptosis, lysosomal imbalance, and lipofuscin production, resulting in photoreceptor cell destruction and consequently, age-related visual impairment such as AMD.” See Conclusion, par. 1st. Li explains that 4-HNE is a potential target for therapy aimed to delay aging related diseases.
Shapiro teaches MDA and HNE are common toxic aldehydes and therapies aimed at lowering these aldehydes in AMD patients represents a novel strategy for potential treatment. See p1, 3rd par.
It would have been prima facie obvious to a person having ordinary skill in the art prior to the filing of the instant application to arrive at the claimed methods in view of Machatha, Li, and Shapiro. One would be motivated to do so because the claimed compound is taught to treat conditions in which toxic aldehydes are implicated in the pathogenesis. The claimed compound is taught to scavenge toxic aldehydes including 4-HNE and MDA. The primary amine is taught to scavenge MDA and 4-HNE. See Table 1, compound 1. It is thought that the claimed compound reacts with MDA and HNE, among other toxic aldehydes, to reduce or eliminate their ability to react with proteins, lipids, carbohydrates, and DNA. See par. 121. They form a closed structure thereby trapping the aldehydes. Such action will treat conditions including macular degeneration, SLS, ichthyosis, and numerous neurodegenerative and neurological conditions. As such, administration of the claimed compound at a dosage that is taught to be administered systemically and inhibit the activity of HNE and MDA has a reasonable and predictable expectation of success. This is further reenforced by Shapiro, which teaches lowering MDA and HNE to be a novel treatment strategy for AMD. Not only are the claimed dosages taught, but the mechanism of action and route of administration are taught to inhibit MDA and HNE, which is certainly implicated in each of the claimed conditions. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985); and 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).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-7 and 9-19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Patent No. 10,543,181. The claims of the ‘181 patent are directed to administration of a compound of Formula (I) that encompasses the claimed compound. Table 1 @ col. 50 shows the claimed compound as compound 3. Thus, it is preferred in Formula (I). Further, the claims are directed to treating ichthyosis associated with SLS. See claim 1 of the ‘181 patent. The route of administration is not claimed in claim 1 and the Specification supports systemic, oral, transdermal, and other routes of administration. Thus, in light of the disclosure, the claims are directed to treating the same subject with the same agent through the same mode of action. While percentages are claimed of API, a POSA would be able to optimize to arrive at the claimed dosages. See M.P.E.P. § 2144.05.
Claims 1-6 and 9-18 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Patent No. 11,771,664. The claims of the ‘664 patent are directed to administration of a compound of Formula (I) that encompasses the claimed compound. Table 2 @ col. 52 shows the claimed compound as compound 10. Thus, it is preferred in Formula (I). Further, the claims are directed to treating ichthyosis associated with SLS. See claim 1 of the ‘664 patent. The route of administration is not claimed in claim 1 and the Specification supports systemic, oral, transdermal, and other routes of administration. Thus, in light of the disclosure, the claims are directed to treating the same subject with the same agent through the same mode of action. While percentages are claimed of API, a POSA would be able to optimize to arrive at the claimed dosages. See M.P.E.P. § 2144.05.
As such, no claim is allowed.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JARED D BARSKY whose telephone number is (571)272-2795. The examiner can normally be reached on 9-5 M-F.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amy Clark can be reached on 571-272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JARED BARSKY/Primary Examiner, Art Unit 1628
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