DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . Preliminary amendment filed on 07/20/2023 has been entered. Claims 1-21 are pending in this application. Claims 19 and 21 are withdrawn. Claims 1-18 and 20 are currently under examination.
Priority
This application is a 371 of PCT/EP2021/062293 filed on 05/10/2021 and claims foreign priority of GERMANY 102020112603.4 filed on 05/10/2020.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-(d) prior to declaration of an interference, a certified English translation of the foreign application must be submitted in reply to this action. 37 CFR 41.154(b) and 41.202(e). Failure to provide a certified translation may result in no benefit being accorded for the non-English application.
Election/Restrictions
Applicant's election without traverse of Group I invention (claims 1-18 and 20) and species (A. as specific solute or mixture thereof: ectoine and its derivatives of formula I and/or II and the physiologically compatible salts, amides and esters of the aforementioned compounds; B. as specific ss(+)RNA viral disease and coexist condition or disease: SARS-CoV-1 and chronic respiratory disease; C. as specific form of composition: liquid form suitable for use with a nebulizer and/or respirator) in the reply filed on 08/18/2025 is acknowledged. Claims 19 and 21 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention or species, there being no allowable generic or linking claim. Thus, claims 1-18 and 20 are currently under examination.
Information Disclosure Statement
The information disclosure statement (IDS) filed on 11/10/2022 has been considered. The annotation “(accessed in 2022)” is inserted into the cite No 3 and 4 of NPL as year is required.
Claim Objections
Claims 1, 3-10, 13, 16, 17, and 20 are objected to because of the following informalities: In claim 1, change the mis-spelled “Coronavriridae” (line 2) to “Coronaviridae”. In claim 3, insert the missing phrase “the group consisting of” immediately after the recitation “selected from” (line 2) to comply with Markush group format ending with the conjunction “and” before the last species; replace the incorrect recitation “ectoine and its derivatives of formula I and/or II and the physiologically compatible salts, amides and esters of the aforementioned compounds, wherein in formula I and in formula II” (lines 4-6) with “ectoine, formula I, formula II, physiologically compatible salts, amides and esters thereof,” because formula I or formula II encompasses ectoine, the conjunction “and” should be placed before the last species to comply with Markush group format, and the chemical structures should be annotated; change the comma “,” at the end of each R group to semicolon “;” to separate from the comma “,” within the R group; and insert the missing semicolon “;” immediately before the recitation “n = 1” (line 11). In claim 4, change the incorrect recitation “Betacoronavirus and/or Alphacoronavirus” (line 3) to “Betacoronavirus or Alphacoronavirus” because the same RNA virus cannot be classified under two different gena. In claim 5, insert the missing phrase “the group consisting of” immediately after the recitation “selected from” (line 3) and change the conjunction “and/or” (line 4) to “and” to comply with Markush format. In claims 6 and 7, insert the missing phrase “course of” immediately before the recitation “the disease” (line 2 of claims 6 and 7) to describe the subsequent infection or inflammation in the epithelial tissues or endothelium. In claim 8, change the incorrect recitation “uses this protein” (lines 3 to 4) to “uses the least one membrane-bound protein” to be consistent with preceding clause. In claim 9, insert the missing phrase “the group consisting of” immediately after the recitation “selected from” (line 3) and change the conjunction “and/or” (line 4) to “and” to comply with Markush format. In claim 10, change the incorrect recitation “unfolding and/or opening” (line 3) to “unfolding or opening” because the “and” duplicates the scope. In claim 13, insert the missing word “other” immediately before the recitation “anti-viral compounds” (line 3) because the preceding solute is also anti-viral compound; and change the incorrect conjunction “and/or” (line 4) to “or” because the “and” overlaps scopes of the preceding gena. In claim 16, change the incorrect conjunction “and” (lines 3, 5, and 6) or “and/or” (line 5) to “or” because the composition cannot be in different forms at the same time. In claim 17, change the incorrect recitation “for solution” (line 2) to “as solution”; and replace the incorrect conjunction “and/or” (line 3) with “or” because the liquid cannot be used with two different devices at the same time. In claim 20, change the incorrect recitation “and/or” (line 6) to “or” because the “and” overlaps scopes of preceding steps. Appropriate correction is required.
Claim 1 is objected to because they include reference characters which are not enclosed within parentheses. Reference characters corresponding to elements recited in the detailed description of the drawings and used in conjunction with the recitation of the same element or group of elements in the claims should be enclosed within parentheses so as to avoid confusion with other numbers or characters which may appear in the claims. See MPEP § 608.01(m). Applicant is advised to insert “ (I) ” and “ (II) ” underneath the corresponding chemical structures.
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 1-18 and 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 treating a disease caused by a ss(+)RNA virus of the Coronaviridae family”, does not reasonably provide enablement for preventing a disease caused by a ss(+)RNA virus of the Coronaviridae family. 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. Claims 2-9, 12-18, and 20 depend from claim 1.
Applicants claim a method of preventing a disease caused by a ss(+)RNA virus of the Coronaviridae family in a patient recited in claims 1, 10, and 11. However, no limiting definition of “preventing" or “prevention” is given in the instant Specification. In the absence of a limiting definition by the Applicants, "prevention" as described according to the Institute for International Medical Education (pages 15 and 16), is a preventive measure, such as preserving physical fitness in primary prevention and effective intervention to correct departures from good health in secondary prevention. More specifically, tertiary prevention, which is most relevant as used in the context of the instant invention, "consists of the measures available to reduce or eliminate long-term impairments and disabilities, [and to] minimize suffering caused by existing departures from good health". Thus, the claimed method of a disease caused by a ss(+)RNA virus of the Coronaviridae family in a patient as interpreted by a skilled practitioner of the medical or pharmaceutical arts would be to reduce for long-term the occurrence of or to eliminate a disease caused by a ss(+)RNA virus of the Coronaviridae family in a patient by the method.
The Applicant's attention is drawn to In re Wands, 8 USPQ2d 1400 (CAFC1988) at 1404 where the court set forth eight factors to consider when assessing if a disclosure would have required undue experimentation. Citing Ex parte Forman, 230 USPQ 546 (BdApls 1986) at 547 the court recited eight factors: (1) The nature of the invention; (2) the state of the prior art; (3) the relative skill of those in the art; (4) the predictability or unpredictability of the art; (5) the breadth of the claims; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary.
All of the Wands factors have been considered with regard to the instant claims, with the most relevant factors discussed below.
Nature of the invention: The rejected invention is drawn to A method of preventing or treating a disease caused by a ss(+)RNA virus of the Coronaviridae family, said method comprising administering to a patient in need thereof a composition comprising at least one compatible solute or solute mixture, wherein the at least one compatible solute or solute mixture is selected from organic and highly water soluble compounds (claim 1), wherein the at least one compatible solute reduces or prevents the unfolding (claim 10) or wherein multiplication of the ss(+)RNA virus is reduced or prevented (claim 11).
Relative skill of those in the art: The relative skill of those in the art is from biomedical field (see the cited reference below).
Breadth of claims: The claim is extremely broad in that it encompasses the prevention of a disease caused by a ss(+)RNA virus of the Coronaviridae family in a patient using the claimed method.
State of the prior art/Predictability or unpredictability of the art: There is no teaching or suggestion in the state of the prior art that application of certain pharmaceutical method can prevent a disease caused by a ss(+)RNA virus of the Coronaviridae family in a patient. El-Abd (J Gynecol Res Obstet 6(1): 002-003, 2020, Published: 24 April, 2020, also listed in IDS filed on 11/10/2022) disclosed that Ectoine, a compatible solute with no detectable cytotoxicity so far, proven to modulate the inflammatory response in lungs and would prove potential adjuvant therapy for COVID-19. Clinical trials are required to test the validity of these drugs to attenuate the COVID-19 sever events (page 002, right column, paragraphs 2 to 3). One of skilled artisan would understand that contemporary treatment or management of a disease caused by a ss(+)RNA virus of the Coronaviridae family in a patient by a compatible solute is to minimize symptoms of, not to prevent, a disease caused by a ss(+)RNA virus of the Coronaviridae family.
Amount of guidance/Existence of working examples: It is worth noting that there are no working examples in the instant application to show that the claimed method is effective for preventing a disease caused by a ss(+)RNA virus of the Coronaviridae family in a patient as recited in the claim. The exemplary embodiments of the Specification merely present in vitro assays (Examples 1-7) and formulation of the solute (Example 8).
Quantity of experimentation: In order to practice the full scope of the invention, one skilled in the art would need to undertake a novel and extensive research program to show that a preventive measure can be achieved after applying the claimed method. Furthermore, one of ordinary skill in the art would need to test a representative number of animals before one of ordinary skill in the art would be able to conclude that any method can be used to prevent a disease caused by a ss(+)RNA virus of the Coronaviridae family. Because this research would have to be exhaustive, and because it would involve such a wide and unpredictable scope of use in prevention of a disease caused by a ss(+)RNA virus of the Coronaviridae family, it would constitute an undue and unpredictable experimental burden.
Lack of a working example is a critical factor to be considered, especially in a case involving an unpredictable and undeveloped art. See MPEP § 2164. Genetech, 108 F.3d at 1366, 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 as discussed above, including the amount of guidance provided and the predictability of the art and the lack of working examples to practice the full scope of the claimed invention herein, a person of ordinary skill in the art would have to engage in undue experimentation, with no assurance of success.
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 1-18 and 20 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 pre-AIA the applicant regards as the invention. Claims 2-5, 7-9, 11, 13-15, and 17 depend from claim 1.
The term “highly water soluble” (line 6 of claim 1) is a relative term which renders the claim indefinite. The term “highly water soluble” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Also, the scope of the recitation “organic… water soluble compounds” is unclear. To advance prosecution, the recitation is broadly interpreted as “any water-soluble organic compound”.
Claims 6 and 12 recite “transitional” (line 3 of claims 6 and 12), which is not defined and thus is not clear what tissue it is. Applicant is advised to change the above recitation to “topical”.
Claim 10 recites “the unfolding and/or opening of the viral protein” (line 3). Since the “unfolding” and “opening” are not specifically defined in the specification, the “unfolding” overlaps the scope of “opening”, and thus the conjunction “and” is confusing. Applicant is advised to change the recitation “and/or” (line 3) to “or”.
Claim 16 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential structural cooperative relationships of elements, such omission amounting to a gap between the necessary structural connections. See MPEP § 2172.01. The omitted structural cooperative relationships are: Claim 16 recites “the composition is in… i) a solid form… ii) a liquid form… iii) as a mixture”. It is not clear what the relationship of “as a mixture” to preceding “is in”, “a solid form”, and “a liquid form”. Applicant is advised to change the recitation “as a mixture” (line 6) to a solid or liquid form”.
Claims 18 and 20 recite the limitation "claim 15, wherein an infusion is" (line 2 of claim 18) or “claim 15, wherein… the controlled delivery” (line 2 of claim 20). There is insufficient antecedent basis for this limitation in the claim. Applicant is advised to insert the phrase “for a controlled delivery” immediately after the recitation “wherein the composition” (line 1 of claim 16); and change the recitation “claim 15, wherein” (line 2 of claim 18; lines 1 to 2 of claim 20) to “claim 16, wherein”.
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.
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 1-18 and 20 are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Turner et al. (US 2011/0000480, Jan. 6, 2011, hereinafter referred to as Turner ‘480).
With regard to structural limitations “a method comprising administering to a patient (or who has a chronic respiratory disease, elected) in need of treating a disease caused by a ss(+)RNA virus of the Coronaviridae family (or the genus Betacoronavirus; or SARS-CoV-1, elected) a composition comprising at least one compatible solute or solute mixture selected from water-soluble organic compounds (or mannosylglycerate (Firoin), mannosylglyceramide (Firoin-A), ectoine (elected), or formula I; or in combination with other anti-viral compounds; or in an amount of greater than or equal to 0.0001 % by weight to less than or equal to 70 % by weight; or in a liquid form of spray, aerosols or inhalants suitable for use with a nebulizer or respirator, or in combination with infusion; or to be inhaled via the mouth and/or nose)” (claims 1, 3-5, 13-18, and 20):
Turner ‘480 disclosed treatment of Severe Acute Respiratory Syndrome (SARS), Family: Coronaviridae. SARS has recently emerged in the human population as a fatal respiratory disease. A newly discovered Coronavirus, SCV, has been identified as the primary cause of SARS. SARS patients have been treated empirically with a combination of Ribavirin, Oseltamivir, antibiotics and corticosteroids, with mixed results. Treatment with recombinant human interferon (Alfacon R) has shown clinical promise. Groups of 10 mice were administered 50 µl of Ad5-IFNα (murine, 106 PFU) by intranasal (IN) once at 14, 7, 5, or 3 days pre-virus exposure (PVE). In addition, groups of 10 mice were administered 50 µl of Ad5-IFNα (murine, 106 PFU or 105 PFU) IN one time at 6, 12, 24 hours post virus exposure. Treatment with Ad5-IFNα (murine) resulted in complete protection of all animals in the treatment groups. The route of Ad5-IFNα exposure was by intranasal (IN) to simulate respiratory mucosal surface delivery—a proposed route of administration in humans. In a preferred embodiment, the excipient is one that is capable of stabilizing the IFN-encoding delivery vehicle (e.g., the Ad5-IFN delivery vehicle) for an extended period of time at room temperature with a loss of less than 20% of the viral titer or biological activity. Non-limiting examples of such excipients include, e.g., trehalose, sorbitol. sucrose, mannitol, glycine, CaCl2, hydroxyectoine (=
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), ectoine, firoin, firoin A and gelatine. In yet other embodiments, the excipient, which is present in the composition in an amount in the range of from 1% to 90% by weight (e.g., in an amount in the range of from 5% to 30% by weight). In still other embodiments, the composition can be formulated for aerosolized delivery and can be admixed with a pharmaceutically acceptable liquid to form the liquid or gel (page 39/52, [0213-0215 and 0204]; page 15/52, [0012-0014]). This composition can be administered to a subject either prior to viral exposure or within 48 hours of exposure. The antihistamine helps to reduce any nasal congestion, e.g., stuffed or blocked nasal passages, caused by viral infection or rhinitis, thereby maximizing the distribution of the Ad5-IFN and neuraminidase inhibitor and their absorption by the epithelium of the upper and/or lower respiratory tract (page 38/52, [0200]). Mechanical devices designed for pulmonary and/or nasal delivery of the compositions include nebulizers, metered dose inhalers, and powder inhalers. Parenteral administration includes intra-arterial, intravenous, intraperitoneal, subcutaneous, and intramuscular administration. The preferred method of administration can vary depending on various factors (e.g., the components of the composition being administered and the severity of the condition being treated). (page 35/52, [0164]; page 19/52, [0040]).
Thus, these teachings of Turner ‘480 anticipate Applicant’s claims 1-18 and 20 because (a) a solute as 5% to 30% by weight excipient including hydroxiectoin, ectoin, firoin, and firoin A is included in the Ad5-IFNα composition, (b) the SARS identified before filing of Turner ‘480 in 2010 is SARS-CoV-1, and (c) the recited limitations in claims 2 and 6-12 are either properties of solute or consequence after administering the solute to a patient having a SARS infection. The teachings of Turner ‘480 meet all structural limitations of claimed method and thus would achieve the same intended results of claims 2 and 6-12. In an alternative, skilled artisan would follow the teachings of Turner ‘480 to select specific excipient(s), including hydroxiectoin, ectoin, firoin, and firoin A, for stabilizing anti-coronavirus compound for treating a disease caused by coronavirus infection.
Conclusion
No claims are allowed.
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/YIH-HORNG SHIAO/Primary Examiner, Art Unit 1691