DETAILED ACTION
This office action is in response to applicant’s filing dated April 2, 2026.
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 Claims
Claims 1-7 are pending in the instant application.
Election/Restrictions
Applicant’s election of viral infection, CoViD-19, as the elected pathology species in the reply filed on April 2, 2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 4 and 5 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on April 2, 2026.
Claims 1-3, 6, and 7 are presently under examination as they relate to the elected species: CoViD-19
Priority
The present application is a 371 of PCT/ES2021/070786 10/29/2021 filed on October 29, 2021, which claims benefit of foreign priority to SPAIN P202031082 filed on October 29, 2020.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on November 17, 2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner, except where marked with a strikethrough.
Drawings
Acknowledgement is made of the drawings received on April 28, 2023. These drawings are acceptable.
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 1-3, 6, and 7 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 a method of treating influenza A virus comprising administering AG5, does not reasonably provide enablement for treating any pathology in which an inflammatory reaction associated with a cytokine storm occurs. 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. This is a scope of enablement rejection.
To be enabling, the specification of the patent application must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1561 (Fd. Cir. 1993). Explaining what is meant by "undue experimentation," the Federal Circuit has stated that:
The test is not merely quantitative, since a considerable amount of experimentation is permissible, if it is merely routine, or if the specification in question provides a reasonable amount of guidance with respect to the direction in which experimentation should proceed to enable the determination of how to practice a desired embodiment of the claimed invention. PPG v. Guardian, 75 F.3d 1558, 1564 (Fed. Cir. 1996). As pointed out by the court in In re Angstadt, 537 F.2d 498 at 504 (CCPA 1976), the key word is "undue", not "experimentation".
The factors that may be considered in determining whether a disclosure would require undue experimentation are set forth In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 wherein, citing Ex parte Forman, 230 USPQ 546 (Bd. Apls. 1986) at 547 the court recited eight factors:
1- the quantity of experimentation necessary,
2- the amount of direction or guidance provided,
3- the presence or absence of working examples,
4- the nature of the invention,
5- the state of the prior art,
6- the relative skill of those in the art,
7- the predictability of the art, and
8- the breadth of the claims
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. In re Fisher, 57 CCPA 1099, 1108, 427 F.2d 833, 839, 166 USPQ 18, 24 (1970). Keeping that in mind, the Wands factors are relevant to the instant fact situation for the following reasons:
1. The nature of the invention
Claims 1-3, 6, and 7 recite a method for the treatment of a pathology in which an inflammatory reaction associated with a cytokine storm occurs comprising administering to a subject in need thereof an effective amount of the AG5 compound.
2. The relative skill of those in the art
The relative skill of those in the art is high, generally that of an M.D. or Ph.D. The artisan using Applicant’s invention would generally be a physician with a M.D. degree and several years of experience.
3. The state and predictability of the art
As illustrative of the state of the art regarding the treatment of pathology in which an inflammatory reaction associated with a cytokine storm occurs, the Examiner refers to Jarczak et al (Int. J. Mol. Sci., 2022; 23:11740 pp 1-30).
Jarczak teaches the human innate and adaptive immune systems consist of effector cells producing cytokines (interleukins, interferons, chemokines, and numerous other mediators); usually, a fragile equilibrium of pro- and anti-inflammation effects is maintained by complex regulatory mechanisms; disturbances of this homeostasis can lead to intricate chain reactions resulting in a massive release of cytokines; this may result in a drastic self-reinforcement of various feedback mechanisms, which can ultimately lead to systemic damage, multi-organ failure, or death; not only pathogens can initiate such disturbances, but also congenital diseases or immunomodulatory therapies; due to the complex and diverse interactions within the innate and adaptive immune systems, the understanding of this important clinical syndrome is incomplete to date and effective therapeutic approaches remain scarce (abstract). Jarczak teaches to date, there is no valid definition for the term CS (cytokine storm); it is usually understood to mean an overwhelming immune response characterized by the release of cytokines, including interleukins, interferons, chemokines, and other mediators (page 1, last paragraph); and CS means that the dynamics and quantity of systemically released cytokines cause serious damage in the host organism; however, distinguishing between an appropriate and a pathologically dysregulated inflammatory response in critical illness is difficult or impossible (page 2, 1st paragraph). Jarczak teaches since most of the mediators involved in the CS exhibit pleiotropic downstream effects and, in addition, are often interdependent in their biological activity, an extremely complex dynamic arises; the interaction of the mediators and the signaling pathways triggered by them are neither linear nor uniform; moreover, their quantitative values may indicate the severity of the reactions, but not necessarily pathogenesis, clinical features, and prognosis; this complex interplay highlights the limitations of intervening in the acute inflammatory response based on single mediators and at undifferentiated time points (page 2, 1st paragraph). Jarczak teaches depending on the underlying causes and therapeutic measures, cases of CS differ from each other both in onset and duration (page 4, last paragraph).
Moreover, Jarczak teaches infection with certain viral pathogens is frequently accompanied by an excessive release of cytokines; these include MERS-CoV, influenza virus (e.g., H1N1, H5N1), and hemorrhagic fevers (e.g., Dengue, Ebola, and Crimean-Congo virus infections); different viruses are associated with diverse patterns of cytokine release, but so far, this has not been operationalized in terms of a comprehensive and universally effective therapeutic approach (page 11, 5th paragraph). Jarczak teaches the term CS has re-emerged with the occurrence of the COVID-19 pandemic; although not all mechanisms of SARS-Co V-2 virus-induced lung injury have been fully elucidated to date, CS has almost become synonymous with it, both in the scientific community as well as in the mass media (page 11, last paragraph); among viral and parasitic infections, influenza, hemorrhagic fevers (Dengue, Ebola), malaria, and visceral leishmaniosis are most likely to cause CS; in SARSCoV-2, however, CS does not seem to play a major role other than what has been previously reported at the beginning of the pandemic (page 12, 4th paragraph).
A search of the prior art revealed that AG5 has antiviral activity to influenza A virus. However, there is no teachings that AG5 of the instant claims is useful for treating any pathology encompassed by a pathology in which an inflammatory reaction associated with a cytokine storm occurs.
4. The breadth of the claims
The breadth of the claims is not commensurate in scope with the disclosure.
The scope of the claims are narrow in terms of the compounds claimed to be useful for in the claimed method. However, the scope of diseases encompassed by a pathology in which an inflammatory reaction associated with a cytokine storm occurs is extremely broad.
5. The amount of direction or guidance provided and the presence or absence of working examples
MPEP 2164.03 states: “The scope of the required enablement varies inversely with the degree of predictability involved, but even in unpredictable arts, a disclosure of every operable species is not required. A single embodiment may provide broad enablement in cases involving predictable factors, such as mechanical or electrical elements. In re Vickers, 141 F.2d 522, 526-27, 61 USPQ 122, 127 (CCPA 1944); In re Cook, 439 F.2d 730, 734, 169 USPQ 298, 301 (CCPA 1971). However, in applications directed to inventions in arts where the results are unpredictable, the disclosure of a single species usually does not provide an adequate basis to support generic claims. In re Soll, 97 F.2d 623, 624, 38 USPQ 189, 191 (CCPA 1938). In cases involving unpredictable factors, such as most chemical reactions and physiological activity, more may be required. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970) (contrasting mechanical and electrical elements with chemical reactions and physiological activity). See also In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993); In re Vaeck, 947 F.2d 488, 496, 20 USPQ2d 1438, 1445 (Fed. Cir. 1991). This is because it is not obvious from the disclosure of one species, what other species will work”.
The specification only discloses the effect of AG5 after an infection with SVCV in transgenic Danio rerio larvae. The specification and the prior art appear to be silent on a nexus between inhibition of SVCV of AG5 and its efficacy for treating any pathology in which an inflammatory reaction associated with a cytokine storm occurs in vivo.
That is, where physiological activity is concerned (i.e., the claimed method of treatment), one skilled in the art reasonably would not and properly should not accept in vitro results as support for in vivo activity. Amgen, Inc. v. Chugai Pharmaceutical Co., Ltd., 927 F.2d 1200, 1216-1217, 18 USPQ2d 1016, 1030 (Fed. Cir.), cert. denied, 502 U.S. 856 (1991) (“we hold that the district court erred in accepting the in vitro data as support for claims containing what has been found to be an in vivo limitation”). Therefore, to enable one skilled in the art to use a method of treatment in vivo based solely on in vitro testing some evidence correlating in vivo results to in vitro testing at the pertinent time is required. See In re Brana, 51 F.3d 1560, 1565 USPQ2d 1437, 1442 (Fed. Cir. 1995) (to enable one skilled in the art to use a clinical method based on preclinical testing, the preclinical testing must be shown to be statistically significant) and Cross v. Iizuka, 753 F.2d 1040, 1050-1051, 224 USPQ 739, 747-748 (Fed. Cir. 1985) (preclinical testing activity must at least reasonably correlate to clinical activity to establish utility).
As such, if there is no correlation, then the inhibition of SVCV viral activity examples do not constitute working examples.
While it is understood that the absence of working examples should never be the sole reason for rejecting a claim as being broader than an enabling disclosure, the criticality of working examples in an unpredictable art, such as the treatment of any pathology in which an inflammatory reaction associated with a cytokine storm occurs, and in particular with novel untested compounds, is required for practice of the claimed invention.
6. The quantity of experimentation necessary
As discussed above (see: 3. the state and predictability of the art), there is a high unpredictability in the art of treating any pathology in which an inflammatory reaction associated with a cytokine storm occurs; the instantly claimed compound is only known for use in influenza virus inhibition, as such no biological/pharmacological data is known to be associated with these structures and any pathology in which an inflammatory reaction associated with a cytokine storm occurs. Based on this and in the absence of experimental evidence commensurate in scope with the claims (see: 5. The amount of direction or guidance and the presence or absence of working examples above), the skilled in the art will not accept that a compound of formula I, will be effective in treating any pathology in which an inflammatory reaction associated with a cytokine storm occurs as inferred by the claims and contemplated by the specification because neither the prior art nor the specification disclose any data of AG5 that correlates with the treatment of any pathology in which an inflammatory reaction associated with a cytokine storm occurs.
So, determining if AG5 will be effective in treating any pathology in which an inflammatory reaction associated with a cytokine storm occurs, will require developing assays that correlate with the treatment of any pathology in which an inflammatory reaction associated with a cytokine storm occurs assaying AG5 in these assays, and then further determine their efficacy in a validated animal model.
All this is undue experimentation given the limited guidance and direction provided by Applicants.
7. Conclusion
Accordingly, the inventions of claims 1-3, 6, and 7 do not comply with the enablement requirement of 35 U.S.C 112, first paragraph, since to practice the claimed invention a person of ordinary skill in the art would have to engage in undue experimentation with no assurance of success.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
Claims 1, 2, and 6 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Chen et al (Biol. Pharm. Bull., 2009; 32(8): 1385-1391, cited in a previous Office Action).
Chen teaches the compound DASS (Fig 1):
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320
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which is equivalent to the claimed AG5 compound. Chen teaches DASS has been used clinically in China; and this drug is effective in relieving the symptoms of inflammation, fever, and pain due to bacterial and viral infections (page 1385, left, last bridge paragraph). Moreover, Chen teaches the activity of DASS on influenza and avian influenza viruses both in vivo and in vitro were evaluated (page 1385, right, last bridge paragraph) and to determine the therapeutic efficacy against the influenza A virus, mice (10/group) infected with H9N2 virus were treated orally twice daily for 7 d with the test agent beginning 24 h before viral exposure and 4, 24, 48, and 72 h after viral exposure (page 1386, right, 6th paragraph). Influenza A reads on a pathology in which an inflammatory reaction associated with a cytokine storm occurs as evidenced by D’Elia et al (Clinical and Vaccine Immunology, 2013; 20(3):319-327). D’Elia teaches influenza virus trigger life-threatening “cytokine storms” in the host which can result in significant pathology and ultimately death (Abstract) and one of the most studied examples of an organism that can cause cytokine storms is influenza A virus (page 320, right, last paragraph). Thus, Chen teaches a method of treating a pathology in which an inflammatory reaction associated with a cytokine storm occurs, a viral infection (influenza A virus), comprising administering the claimed compound, AG5, orally.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Chen et al (Biol. Pharm. Bull., 2009; 32(8): 1385-1391, cited in a previous Office Action) as applied to claims 1, 2, and 6 above.
As set forth above, Chen teaches a method of treating a pathology in which an inflammatory reaction associated with a cytokine storm occurs, a viral infection (influenza A virus), comprising administering the claimed compound, AG5, orally. Moreover, Chen teaches DASS was administered in 2000, 1000, 500, 250, and 125 mg/kg/d or 2, 1, 0.5, 0.25, and 0.125 mg/kg/day. Chen does not explicitly teach the dosing regimen of instant claim 7.
However, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the invention to utilize the amounts and dosing regimen of DASS taught by Chen as a starting point for optimizing the amount and treatment regimen of DASS/AG5 utilized to treat influenza A virus since Chen teaches DASS/AG5 is useful for treating influenza virus A and because dosage and treatment regimen are result-effective variables, i.e. a variable that achieves a recognized result. Therefore, the determination of the optimum or workable dosages would have been well within the practice of routine experimentation by the skilled artisan. Furthermore, absent any evidence demonstrating a patentable difference between the compositions and the criticality of the claimed dosage range, the determination of the optimum or workable dosing regimen given the guidance of the prior art would have been generally prima facie obvious to the skilled artisan. Please see MPEP 2144.05 [R-2](II)(A) and In re Aller, 220 F. 2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). ("[W]here the general conditions of claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.").
Taken together, all this would result in the practice of the method of claim 7 with a reasonable expectation of success.
Conclusion
Claims 1-3, 6, and 7 are rejected.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RAYNA B RODRIGUEZ whose telephone number is (571)272-7088. The examiner can normally be reached 8am-5:00pm, Monday - Thursday.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amy L Clark can be reached at 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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/Rayna Rodriguez/ Primary Examiner, Art Unit 1628
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