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 .
Election/Restrictions
Amendments to claims renders the restriction requirement moot.
Amended claims 16, 18-31 are pending.
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.
Previously presented rejection of claim(s) 16, 18-31 rejected under 35 U.S.C. 103 as being unpatentable over Harbige US 10576086 is maintained for reasons of record.
Applicant’s arguments:
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Response:
Applicants arguments are not persuasive.
As to the ambiguity with respect to statue under which the rejection is made:
Applicant overlooks ‘
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To hammer home the idea that the compounds are previously known, this phrase is replaced with -- Harbige teaches the active ingredients of the claimed method—in this action.
Pointing out at once apparent typographical error, Applicant states that
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The phrase
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now reads
--Thus the active ingredients and the disease being treated in the claimed method are the same as taught by Harbige.--
As to the amendments to the base claim
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--
Harbige teaches Abstract:
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Harbige teaches at column 1
(3) IFN-γ is a cytokine that is involved in pathogenic immunity, and plays an important role in macrophage activation, and in the upregulation of class I and II major histocompatibility complex (MHC) antigens. It is produced by natural killer (NK) T cells, by CD4 T helper 1 (T.sub.h1) cells, and also by CD8 cytotoxic T lymphocytes (CTL) effector T cells.
(4) One of the crucial roles of IFN-γ is in immunomodulation and immunostimulation. Autoinflammatory and autoimmune conditions can be associated with overproduction or imbalances in IFN-γ secretion, whilst IFN-γ itself has been used to treat patients with immunodeficiencies such as chronic granulomatous disease. IFN-γ has, for example, been implicated in Alzheimer's disease and prion-related diseases (Bate et al; Journal of Neuroinflammation; 2006, 3:7, doi:10.1186/1742-2094-3-7), multiple sclerosis (Traugott et al; Annals of Neurology, 24(2), 1988, 243-251), and epilepsy (Sinha et al; Epilepsy Research, 2008, 82(2-3), 171-176).
(5) A number of cyclic diazo and triazo compounds have been previously reported as being antifolates, and also voltage dependent sodium channel blockers, for example as described in WO 2008/007149, WO 2009/090431, WO 2011/004195 and WO 2011/004196. Disorders in mammals that are said to be treatable by sodium channel blocking include epilepsy, multiple sclerosis, glaucoma and uveitis, cerebral traumas and cerebral ischemias, stroke, head injury, spinal cord injury, surgical trauma, neurodegenerative disorders, motor neurone disease, Alzheimers disease, Parkinsons disease, chronic inflammatory pain, neuropathic pain, migraine, bipolar disorder, mood anxiety, cognitive disorders, schizophrenia and trigeminal autonomic cephalalgias. Antifolates can be used to treat mammalian cancers, and can also act as antimalarials against Plasmodium vivax and Plasmodium falciparum malaria, especially in humans.
(6) There remains a need for compounds that can modulate the production of the pro-inflammatory cytokine IFN-γ, so that medical conditions and diseases that are related to its presence or over-production can be treated or controlled.
Previous action corrected for Applicant pointed out typographical errors:
Harbige teaches compounds falling under the scope of the instant formula of base claim 16:
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Harbige teaches the active ingredients of the claimed method. For example the last compound pictured above is the first compound at the top of numbered page 5 of the instant dependent claim 28.
According to Harbige, column 1, lines 57-60 can modulate the production of the pro-inflammatory cytokine IFN-γ, so that medical conditions and diseases that are related to its presence or over-production can be treated or controlled.
More specifically Harbige teaches, column 1, line 64 on to column 2 line 2 , the compounds are for use in the treatment or control of medical conditions and diseases that are treatable or controllable by inhibiting interferon gamma (IFN-γ) production.
Harbige does not use the language
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for the disease states for use of the above-mentioned compounds.
However, as admitted to by the Applicant the fancy language at the bottom of page 1, Cytokine storm syndrome refers to a group of disorders, representing a variety of inflammatory etiologies with the final common result of overwhelming systemic inflammation, hemodynamic instability, multiple organ dysfunction, and potentially death. More specifically, according to Applicant that Interferon-gamma, is associated with cytokine storm, see page 2, lines 3-5.
Thus the active ingredients and the disease being treated in the claimed method are the same as taught by Harbige. As such the issue here is not even ‘new use for old compound’. Therefore Harbige teaching is anticipatory. Dependent claim limitations are drawn to compounds falling under the scope of the formula of the base claims.
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.
Previously presented rejection of claim(s) 16, 18-31 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2 of U.S. Patent No. 10576086 is maintained.
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Claims 16, 18-31 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 17921036 (reference application) further in view of Harbige US 10576086 Although the claims at issue are not identical, they are not patentably distinct from each other because the conflicting claim is drawn to overlapping subject matter as explained below:
17921036 examined claim 1:
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The active ingredient in the above 17921036 method is at the top of instant dependent claim 28, numbered page 5.
The difference is that the instant claimed method depends on the inherent to the inhibition method claimed in 17921036, as taught by Harbige. That is the inherent property of the active ingredient is same in the claimed methods in both cases.
The teachings of Harbige (discussed under section Claim Rejections - 35 USC § 103) is invoked here.
Harbige teaches Abstract:
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Harbige teaches at column 1
(3) IFN-γ is a cytokine that is involved in pathogenic immunity, and plays an important role in macrophage activation, and in the upregulation of class I and II major histocompatibility complex (MHC) antigens. It is produced by natural killer (NK) T cells, by CD4 T helper 1 (T.sub.h1) cells, and also by CD8 cytotoxic T lymphocytes (CTL) effector T cells.
(4) One of the crucial roles of IFN-γ is in immunomodulation and immunostimulation. Autoinflammatory and autoimmune conditions can be associated with overproduction or imbalances in IFN-γ secretion, whilst IFN-γ itself has been used to treat patients with immunodeficiencies such as chronic granulomatous disease. IFN-γ has, for example, been implicated in Alzheimer's disease and prion-related diseases (Bate et al; Journal of Neuroinflammation; 2006, 3:7, doi:10.1186/1742-2094-3-7), multiple sclerosis (Traugott et al; Annals of Neurology, 24(2), 1988, 243-251), and epilepsy (Sinha et al; Epilepsy Research, 2008, 82(2-3), 171-176).
(5) A number of cyclic diazo and triazo compounds have been previously reported as being antifolates, and also voltage dependent sodium channel blockers, for example as described in WO 2008/007149, WO 2009/090431, WO 2011/004195 and WO 2011/004196. Disorders in mammals that are said to be treatable by sodium channel blocking include epilepsy, multiple sclerosis, glaucoma and uveitis, cerebral traumas and cerebral ischemias, stroke, head injury, spinal cord injury, surgical trauma, neurodegenerative disorders, motor neurone disease, Alzheimers disease, Parkinsons disease, chronic inflammatory pain, neuropathic pain, migraine, bipolar disorder, mood anxiety, cognitive disorders, schizophrenia and trigeminal autonomic cephalalgias. Antifolates can be used to treat mammalian cancers, and can also act as antimalarials against Plasmodium vivax and Plasmodium falciparum malaria, especially in humans.
(6) There remains a need for compounds that can modulate the production of the pro-inflammatory cytokine IFN-γ, so that medical conditions and diseases that are related to its presence or over-production can be treated or controlled.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The art made of record and not relied upon is considered pertinent to applicant's disclosure.
US9862691 Cyclic Triazo And Diazo Sodium Channel Blockers
US9422253 Cyclic Triazo And Diazo Sodium Channel Blockers
US8691818 Cyclic Triazo And Diazo Sodium Channel Blockers
Feldman, Understanding ‘Evergreening’ : Making Minor Modifications Of Existing
Medications To Extend Protections, Health Affairs June 2022 41:6, 801-804.
Dwivedi, Evergreening: A deceptive device in patent rights, Technology in Society 32, (2010) 324–330.
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.
Previously presented rejection of claim(s) 16, 18-31 rejected under 35 U.S.C. 112, first paragraph, because the specification, while being enabling for the compound of the formula and its salts, does not reasonably provide enablement for making solvates of the compound is maintained for reasons of record.
Applicant’s arguments focus on ‘reasonable amount of experimentation’ is not undue.
Applicants arguments that the
. 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.
The determination that "undue experimentation" would have been needed to make and use the claimed invention is not a single, simple factual determination. Rather, it is a conclusion reached by weighing all the relevant factual considerations.
Enablement is considered in view of the Wands factors (MPEP 2164.01 (a)). These include: (1) breadth of the claims; (2) nature of the invention; (3) state of the prior art; (4) amount of direction provided by the inventor; (5) the level of predictability in the art; (6) the existence of working examples; (7) quantity of experimentation needed to make or use the invention based on the content of the disclosure; and (8) relative skill in the art.
All of the factors have been considered with regard to the claims, with the most relevant factors discussed below:
The specification does not reasonably provide enablement for making solvates of the claimed compounds. The specification does not enable any person skilled in the art of synthetic organic chemistry to make the invention commensurate in scope with these claims. The factors to be considered in making an enablement rejection have been summarized above. In the present case the important factors leading to a conclusion of undue experimentation are the absence of any working example of a formed solvate, the lack of predictability in the art, and the broad scope of the claims. There is no working example of any solvate or solvate formed. None of the compounds made (based on data provided) form solvates. The compounds of the claims are made as per prior art teaching acknowledged at page 11, lines 23-34. Thus, the compounds are not Applicants invention. The claims are drawn to solvates, yet the numerous examples presented all failed to produce a solvate. These cannot be simply willed into existence. As was stated in Morton International Inc. v. Cardinal Chemical Co., 28 USPQ2d 1190 "The specification purports to teach, with over fifty examples, the preparation of the claimed compounds with the required connectivity. However ... there is no evidence that such compounds exist.., the examples of the '881 patent do not produce the postulated compounds.., there is ... no evidence that such compounds even exist." The same circumstance appears to be true here. There is no evidence that solvates of these compounds actually exist; if they did, they would have formed. Hence, applicants must show that solvates can be made, or limit the claims accordingly. g) The state of the art is that is not predictable whether solvates will form or what their composition will be. In the language of the physical chemist, a solvate of organic molecule is an interstitial solid solution. This phrase is defined in the second paragraph on page 358 of West (West, Solid State Chemistry and Its Applications, john Wiley & Sons, 1984). The solvent molecule is a species introduced into the crystal and no part of the organic host molecule is left out or replaced. In the first paragraph on page 365, West (Solid-State Chemistry) says, "it is not usually possible to predict whether solid solutions will form, or if they do form what is their compositional extent". Thus, in the absence of experimentation one cannot predict if a particular solvent will solvate any particular crystal. One cannot predict the stoichiometry of the formed solvate, i.e. if one, two, or a half a molecule of solvent added per molecule of host. In the same paragraph on page 365 West (Solid State Chemistry) explains that it impossible to make meta-stable non-equilibrium solvates, further clouding what Applicants mean by the word solvate. Compared with polymorphs, there is an additional degree of freedom to solvates, which means a different solvent or even the moisture of the air that might change the stabile region of the solvate. h) The breadth of the claims includes all of the hundreds of thousands of compounds of formula (I) as well as the presently unknown list of solvents embraced by the term "solvate". Thus, the scope is broad.
MPEP 2164.01(a) states, “A conclusion of Iack 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. ln re Wright, 999 F.2d 1557,1562, 27 USPQ 2d 1510, 1513 (Fed. Cir. 1993).'' That conclusion is clearly justified here. Thus, undue experimentation would be required to make and use Applicants' invention.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NIZAL S CHANDRAKUMAR whose telephone number is (571)272-6202. The examiner can normally be reached M-F 8-5 EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Andrew Kosar can be reached at (571) 272-0913. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/NIZAL S CHANDRAKUMAR/Primary Examiner, Art Unit 1625
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