DETAILED ACTION
Status of Claims
The amendment submitted June 22, 2023 has been entered.
Claims 28-43 are pending and under consideration.
Claims 28-43 are new.
Claims 1-27 are cancelled by Applicant.
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 .
Priority
This application is a 371 National Phase Application of PCT/IL2021/051533 filed December 24, 2021, which claims the benefit of priority to Israeli Patent Application No. IL279765, filed on December 24, 2020.
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d), and the certified copy has been filed.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
One information disclosure statements (IDS) submitted on June 22, 2023 is acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Specification
Abstract Objections
Applicant is reminded of the proper content of an abstract of the disclosure.
A patent abstract is a concise statement of the technical disclosure of the patent and should include that which is new in the art to which the invention pertains. The abstract should not refer to purported merits or speculative applications of the invention and should not compare the invention with the prior art.
If the patent is of a basic nature, the entire technical disclosure may be new in the art, and the abstract should be directed to the entire disclosure. If the patent is in the nature of an improvement in an old apparatus, process, product, or composition, the abstract should include the technical disclosure of the improvement. The abstract should also mention by way of example any preferred modifications or alternatives.
Where applicable, the abstract should include the following: (1) if a machine or apparatus, its organization and operation; (2) if an article, its method of making; (3) if a chemical compound, its identity and use; (4) if a mixture, its ingredients; (5) if a process, the steps.
Extensive mechanical and design details of an apparatus should not be included in the abstract. The abstract should be in narrative form and generally limited to a single paragraph within the range of 50 to 150 words in length.
See MPEP § 608.01(b) for guidelines for the preparation of patent abstracts.
The abstract of the disclosure is objected to because the abstract is less than 50 words. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 28-43 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claims contain subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
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." These factors include, but are not limited to: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. See MPEP § 2164.01 (a).
Upon consideration of the factors discussed below, the examiner concludes that one skilled in the art could not practice the invention without being burdened with undue experimentation based on the information provided by the applicant.
A discussion of these factors they relate to the pending claims follows.
Breadth of Claims and Nature of the Invention
Claims 28-43 are directed towards methods of “of treating or preventing a viral respiratory infection or disease, disorder or condition caused by a viral respiratory infection in a subject, comprising administering a composition comprising plant-derived or fungus-derived compounds to the subject.”
Applicant defines “viral respiratory infection” on page 9 as “The term "respiratory virus (RV)" as used herein refers to a submicroscopic infectious agent that replicates inside the living cells of an organism (a host) and which affects the upper respiratory tract and/or the lower respiratory tract. The term encompasses both single-stranded and double-stranded DNA- and RNA-viruses. Non- limiting examples of RVs include adenovirus, bocavirus, coronavirus, enterovirus, influenza virus, parainfluenza virus, parvovirus, pneumovirus, respiratory syncytial virus (RSV), and rhinovirus. Accordingly, diseases, disorders or pathological conditions caused by viral respiratory infections that can be treated or prevented according to the invention include, but are not limited to, viral infections that affect the upper and/or lower respiratory tracts, common cold, seasonal cold, influenza (flu), severe acute respiratory syndrome (SARS), coronavirus disease, pharyngitis, tonsillitis, laryngitis, sinusitis, bronchitis, bronchiolitis, viral pneumonia, acute otitis media, and croup (laryngotracheobronchitis).”
It is well-known in the art of virology that viruses are not homogenous entities and are incredibly diverse with respect to genetic makeup, structure, replication mechanism, host interactions, and other factors.
Jones et al. explains that “Viral heterogeneity poses a difficult challenge for medicine. Adequate medical interventions are still lacking for many viral infections, particularly the ones discussed in this Review (Jones, Jennifer E., Valerie Le Sage, and Seema S. Lakdawala. "Viral and host heterogeneity and their effects on the viral life cycle." Nature Reviews Microbiology 19, no. 4 (2021): 272-282).”
Jones further explains “Current technologies make it easier than ever before to screen thousands of compounds for efficacy against viral infection and rapidly identify potential new therapeutic candidates. Nevertheless, these results should be interpreted with caution. A given virus may exhibit extraordinary diversity in genomic content and particle morphology, so candidate therapeutics must be pan-protective against a heterogeneous viral population.”
Woolhouse also teaches that “The lines of evidence described earlier combine to suggest the following tentative model of the emergence process for novel human viruses. First, humans are constantly exposed to a huge diversity of viruses, though those of others mammals (and perhaps birds) are of greatest importance. Moreover, these viruses are very genetically diverse and new genotypes, strains and species evolve rapidly (over periods of years or decades).”
Woolhouse also teaches that “There are 219 virus species that are known to be able to infect humans. The first of these to be discovered was yellow fever virus in 1901, and three to four new species are still being found every year. Extrapolation of the discovery curve suggests that there is still a substantial pool of undiscovered human virus species, although an apparent slow-down in the rate of discovery of species from different families may indicate bounds to the potential range of diversity. More than two-thirds of human viruses can also infect non-human hosts, mainly mammals, and sometimes birds. Many specialist human viruses also have mammalian or avian origins. Indeed, a substantial proportion of mammalian viruses may be capable of crossing the species barrier into humans, although only around half of these are capable of being transmitted by humans and around half again of transmitting well enough to cause major outbreaks. A few possible predictors of species jumps can be identified, including the use of phylogenetically conserved cell receptors. It seems almost inevitable that new human viruses will continue to emerge, mainly from other mammals and birds, for the foreseeable future (Woolhouse, M., Scott, F., Hudson, Z., Howey, R. and Chase-Topping, M., 2012. Human viruses: discovery and emergence. Philosophical Transactions of the Royal Society B: Biological Sciences, 367(1604), pp.2864-2871).”
White and Brown additionally explain that “Altogether, there are over 200 human respiratory viruses, falling mainly within six families: orthomyxoviruses, paramyxoviruses, picornaviruses, coronaviruses, adenoviruses, and herpesviruses (see corresponding entries elsewhere in this text).”(White DO, Brown LE. RESPIRATORY VIRUSES. Encyclopedia of Virology. 1999:1488–96. doi: 10.1006/rwvi.1999.0247. Epub 2004 Jun 17. PMCID: PMC7173581).
Leung additionally explains “Human respiratory viruses include a broad range of viruses that infect cells of the respiratory tract, elicit respiratory and other symptoms, and are transmitted mainly by respiratory secretions of infected persons. Respiratory virus infections often cannot be differentiated clinically. Respiratory viruses belong to diverse virus families that differ in viral and genomic structures, populations susceptible to infection, disease severity, seasonality of circulation, transmissibility and modes of transmission.”
(Leung, Nancy HL. "Transmissibility and transmission of respiratory viruses." Nature Reviews Microbiology 19, no. 8 (2021): 528-545).
Therefore, it is reasonable to conclude that the claims are broad with respect to respiratory virus and condition caused by viral respiratory infection. As explained, there are numerous respiratory viruses that are diverse and heterogenous in structure, susceptible populations, transmission and treatment.
On page 10, Applicant defines “subject” as “As used herein, the term “subject” can be a vertebrate, such as a mammal, a fish, a bird, a reptile, or an amphibian. Thus, the subject of the herein disclosed methods can be a human, non-human primate, horse, pig, rabbit, dog, sheep, goat, cow, cat, guinea pig, or rodent. The term does not denote a particular age or sex. Thus, adult and newborn subjects, as well as fetuses, whether male or female, are intended to be covered.”
Consequently, it is reasonable to conclude that the claims are broad with respect to subject.
On page 10, Applicant defines “treatment” or “treating” as “As used herein, the term “treatment” or "treating" refers to the medical management of a patient with the intent to cure, ameliorate, stabilize, or prevent a disease, pathological condition, or disorder. This term includes active treatment, that is, treatment directed specifically toward the improvement of a disease, pathological condition, or disorder, and also includes causal treatment, that is, treatment directed toward removal of the cause of the associated disease, pathological condition, or disorder. In addition, this term includes palliative treatment, that is, a treatment designed for the relief of symptoms rather than the curing of the disease, pathological condition, or disorder; preventative treatment, that is, treatment directed to minimizing or partially or completely inhibiting the development of the associated disease, pathological condition, or disorder; and supportive treatment, that is, treatment employed to supplement another specific therapy directed toward the improvement of the associated disease, pathological condition, or disorder. In various aspects, the term covers any treatment of a subject, and includes: (i) preventing the disease from occurring in a subject that can be predisposed to the disease but has not yet been diagnosed as having it; (ii) inhibiting the disease, i.e., arresting its development; or (iii) relieving the disease, i.e., causing regression of the disease.”
Consequently, based on Applicant’s definition, treatment is inclusive of prevention and or prophylaxis.
On page 11, Applicant defines “preventing” as “As used herein, the term “prevent” or “preventing” refers to precluding, averting, obviating, forestalling, stopping, or hindering a disease, disorder, or pathological condition from happening, especially by advance action.”
Consequently, based on Applicant’s definition, the claims are broad with respect to the goal of “treating or preventing.”
In summary, it is reasonable to conclude that the claims are broad with respect to the respiratory virus, disease, disorder or condition, treating and preventing, and subject.
The state of the prior art
The state of the prior art is what one skilled in the art would have known, at the time the application was filed, about the subject matter to which the claimed invention pertains. The relative skill of those in the art refers to the skill of those in the art in relation to the subject matter to which the claimed invention pertains at the time the application was filed. See MPEP § 2164.05(b). See Pac. Biosciences of Cal., Inc. v. Oxford Nanopore Techs., Inc., 996 F.3d 1342, 1352, 2021 USPQ2d 519 (Fed. Cir. 2021).
The state of the prior art provides evidence for the degree of predictability in the art and is related to the amount of direction or guidance needed in the specification as filed to meet the enablement requirement. The state of the prior art is also related to the need for working examples in the specification. See MPEP § 2164.05 (a).
Applicant’s invention is directed towards using a composition comprising plant-derived or fungus-derived compounds including D-limonene, menthol and linalyl anthranilate to treat or prevent a viral respiratory infection or a disease, disorder, or condition caused by a respiratory virus.
There is no known antiviral present in the art capable of treating and preventing all respiratory viruses in all humans and species claimed. In fact, many viruses do not have treatment or prevention options.
As White and Brown explain “Very successful live attenuated vaccines are in general use against certain ‘respiratory’ viruses like measles, mumps and rubella, which, though naturally transmitted via the respiratory route, are absolutely dependent upon viremic spread to their target organs elsewhere in the body. In contrast, it is a much more challenging assignment to develop effective vaccines against viruses whose pathogenicity is essentially confined to the respiratory tract.”
White and Brown also explains challenges with antivirals: “In the long term another source of hope may lie with antiviral chemotherapeutic agents (see Antivirals), although significant barriers still remaining are (1) the multiplicity of viruses involved and the specific antiviral spectrum of available agents; (2) difficulties with drug delivery, efficacy and toxicity; (3) the fact that high titers of virus may be produced even before the onset of symptoms; and (4) emergence of drug-resistant mutants.”
Boncristiani teaches that “The respiratory viruses that most commonly circulate in all continents as endemic or epidemic agents are influenza virus, respiratory syncytial virus, parainfluenza viruses, metapneumovirus, rhinovirus, coronaviruses, adenoviruses, and bocaviruses. Although vaccines and effective antiviral drugs are not yet available for most of these viruses, much progress has been made in the understanding of their biology and fundamental issues of host–parasite relationship (Boncristiani HF, Criado MF, Arruda E. Respiratory Viruses. Encyclopedia of Microbiology. 2009:500–18. doi: 10.1016/B978-012373944-5.00314-X. Epub 2009 Feb 17. PMCID: PMC7149556).”
By example only, Boncristiani teaches that for human respiratory syncytial virus that “HRSV URIs require no specific treatment, and antibiotics may be considered only in the presence of bacterial complications, such as acute otitis media…The only antiviral drug currently approved for the treatment of infants with HRSV is the synthetic nucleoside ribavirin, delivered by small-particle aerosol via mist tent, mask, oxygen hood, or ventilator.”
By example only, Boncristiani more specifically teaches that for human parainfluenza viruses that “At present, only supportive and symptomatic treatment is available for HPIV infections…. besides anecdotal reports of aerosolized ribavirin treatment of immunocompromised patients with HPIV LRT infections, no specific antiviral treatment is licensed for HPIV. Inhibitors of the protein HN are effective in vitro and in animal models, but have not reached clinical use.”
By example only, Boncristiani more specifically teaches that for human metapneumovirus that “Little is known about HMPV-specific mechanisms of pathogenesis. Animal studies show disruption of the respiratory epithelium, epithelial cell sloughing, and inflammatory infiltrates in the lung” and additionally teaches that “Other than supportive measures, oxygen therapy, bronchodilators, corticosteroids, and mechanical ventilation, there is no specific antiviral treatment for HMPV.”
By example only, Boncristiani more specifically teaches that for adenoviruses that “Up to 50% of nonepidemic adenoviral infections are asymptomatic, and, in fact, adenoviruses were discovered because of their propensity for latency in adenoidal tissue. Symptomatic infections may involve all parts of the respiratory tract and generally initiate in the upper respiratory epithelium,” and additionally teaches that “At present, there is no routine effective antiviral treatment for adenovirus infections.”
By example only, Boncristiani more specifically teaches that for Human Coronaviruses Unrelated to SARS that “Intranasal interferon protects against experimental infection with HCoV-229E, but there is no antiviral drug therapy currently available for non-SARS HCoVs. Considering the usually self-limited course of infection, supportive care and symptomatic relief are sufficient. No vaccines are currently available for HCoV.”
Consequently, Boncristiani teaches there are many respiratory viruses that are difficult to diagnose, have no antiviral or vaccine options, and are not well-understood.
Therefore, it is not reasonable to conclude that the compositions claimed in instant invention would be predicted to generally treat or prevent all respiratory viruses as claimed in all subjects as claimed.
To date, Applicant has provided only limited in vitro data for VERO E6 cells infected with SARS-CoV-2 (CoV2).
Atampugbire teaches limitations associated with relying solely on in vitro data.
Specifically, Atampugbire teaches “Cytotoxicity assay is a technique that is used to measure the degree of cell death caused by the presence of a substance or by a process and employed during the early stages of antibody–drug conjugates development to select promising candidates via in vivo methods…Cytotoxicity assays are often cost-effective tools for drug screening and toxicity assessment (Atampugbire, Gabriel, Eureka Emefa Ahadjie Adomako, and Osbourne Quaye. "In Vitro Antiviral Assays: A Review of Laboratory Methods." ASSAY and Drug Development Technologies 23, no. 4 (2025): 165-179).
Atampugbire also teaches that “A key challenge in in vitro antiviral assays is low reliability of results due to the lack of in vivo factors such as plasma proteins, which may interact with drugs to affect pharmacological outcomes. There are also issues about reproducibility of experimental data due to varying experimental parameters like cell culture conditions… Most antiviral assays focus on single parameters like viral replication, but viruses interact with host cells in complex processes, and a more comprehensive understanding of these interactions is needed for the development of effective antiviral therapies. Multiparametric assays measure multiple properties and provide a more holistic view of viral infections and host responses… In vitro antiviral assays ensure faster and easier screening of compounds for antiviral activity and include techniques ranging from PRA to cutting-edge HCS technologies, for assessing the efficacy and safety of antiviral compounds. However, their inability to mimic a perfect in vivo environment poses a major challenge, and ultimately affects the reliability of in vitro experimental outcomes in drug development.”
Therefore, it is reasonable to conclude that the current state of the art is highly unpredictable, indicating that more details, working examples and guidance would be required to practice the invention as disclosed for the full scope of invention.
(D) The level of one of ordinary skill
The person of ordinary skill in the art is a hypothetical person who is presumed to have known the relevant art at the relevant time. Factors that may be considered in determining the level of ordinary skill in the art may include: (A) "type of problems encountered in the art;" (B) "prior art solutions to those problems;" (C) "rapidity with which innovations are made;" (D) "sophistication of the technology; and" (E) "educational level of active workers in the field. In a given case, every factor may not be present, and one or more factors may predominate." In re GPAC, 57 F.3d 1573, 1579, 35 USPQ2d 1116, 1121 (Fed. Cir. 1995); Custom Accessories, Inc. v. Jeffrey-Allan Indus., Inc., 807 F.2d 955, 962, 1 USPQ2d 1196, 1201 (Fed. Cir. 1986); Environmental Designs, Ltd. V. Union Oil Co., 713 F.2d 693, 696, 218 USPQ 865, 868 (Fed. Cir. 1983). See MPEP § 2141.03 (I)
The invention described pertains to medicine and pharmacology. One of ordinary skill would be a person with training in medicine, veterinary medicine, pharmacology, biochemistry or a related technical discipline.
(E) The level of predictability in the art
The amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). The "amount of guidance or direction" refers to that information in the application, as originally filed, that teaches exactly how to make or use the invention. The more that is known in the prior art about the nature of the invention, how to make, and how to use the invention, and the more predictable the art is, the less information needs to be explicitly stated in the specification. In contrast, if little is known in the prior art about the nature of the invention and the art is unpredictable, the specification would need more detail as to how to make and use the invention in order to be enabling.
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. See MPEP § 2164.03.
Consequently, technologies involving physiological activity as opposed to mechanical or electrical inventions are generally regarded as being unpredictable sciences.
As aforementioned, there are numerous respiratory viruses that diverge based on viral and genomic structures, populations susceptible to infection, disease severity, seasonality of circulation, transmissibility, modes of transmission, and treatment options.
There is to date no general pharmacological agent known to treat all respiratory viruses known in addition to respiratory viruses that are unknown or challenging to diagnose.
This is equally accurate pertaining to a pharmacological agent and its ability to prevent a viral respiratory infection or disease, disorder or condition caused by a viral respiratory infection
Based on these cumulative factors, it is reasonable to conclude that predictability in the art is low.
Consequently, the applicant would need to provide more details, working examples and guidance in order for the claimed invention to be enabling based on the scope and nature of the claimed invention.
The existence of working examples
The applicants’ working examples are directed towards:
Example 1: Cytotoxicity studies using VERO E6 cells infected with SARS-CoV-2.
Applicant has failed to provide working examples and key details encompassing the diverse range of respiratory viruses and subjects claimed, including providing working examples representative for the diversity of viruses, patient populations, treatment regimen, and support for prevention and treatment of a viral respiratory infection or disease, disorder or condition caused by a viral respiratory infection.
Additionally, Applicant has failed to provide working examples supporting prophylactic treatment including identifying populations at risk, recurrence of the respiratory viruses, and other factors commonly associated with developing prophylactic treatment regimens.
On this basis and the prior discussion, the working examples are both not commensurate with the scope of protection sought and are not enabling. One ordinarily skilled in the art would be unable to simply translate the evidence provided by the applicant without undue experimentation across the full scope of the instant invention, particularly virus, patient population, and prevention as claimed.
The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
As aforementioned, the quantity of experimentation depends on the prior art, the predictability of the art, and the direction provided by the inventor, which are factors that were already discussed.
In order for one ordinarily skilled in the art to practice the invention as disclosed, some attributes one would require, but are not limited to:
Studies supporting the composition claimed can treat or prevent viral respiratory infection or disease, disorder or condition caused by a viral respiratory infection across the broad and diverse range of viruses, disease, conditions, and disorders claimed. To date, Applicant has provided minimal experimental data and guidance on how to practice the invention as claimed.
Studies including the patient populations claimed (i.e.: pediatric patients, pregnant mothers, other mammals, avian populations, etc.).
Studies supporting the treatment regimen prescribed (i.e.: dosage, frequency, timing and monitoring, etc.).
Consequently, the examiner concludes that one ordinarily skilled in the art would require undue experimentation in order to practice invention based on the details provided and scope of invention defined in Claims 28-43.
Therefore, claims 28-43 are rejected for lacking enablement commensurate with the scope of the claims.
Conclusion
Claims 28-43 are under consideration and are rejected.
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CAROLYN L. LADD whose telephone number is (703)756-5313. The examiner can normally be reached M-Th, 7:00 am to 5:30 pm EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James H. Alstrum-Acevedo can be reached at 571-272-5548. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/C.L.L./Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622