DETAILED ACTION
Status of Claims
The amendment submitted January 30, 2024 has been entered.
Claims 1-11 and 13-15 are pending and under consideration.
Claims 12 and 16-26 are cancelled by Applicant.
Claims 1-11, 13, and 15 are amended 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/EP2022/051377 filed January 22, 2022, which claims the benefit of priority to European Patent Application No. EP21152993.8, filed on January 22, 2021.
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 September 3, 2024 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.
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 1-11 and 13-15 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 written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Vas-Cath Inc. V. Mahurka, 19 USPQ2d 1111, states that applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention, for purposes of the “written description” inquiry, is “whatever is now claimed” (See page 1117).
A review of the language of the claim indicates that these claims are drawn towards “lonafarnib or a derivative thereof, or solvates, salts, stereoisomers, complexes, polymorphs, crystalline forms, racemic mixtures, diastereomers, enantiomers, tautomers, isotopically labelled forms, prodrugs, and combinations thereof.”
A description of the term "lonafarnib or a derivative thereof, or solvates, salts, stereoisomers, complexes, polymorphs, crystalline forms, racemic mixtures, diastereomers, enantiomers, tautomers, isotopically labelled forms, prodrugs, and combinations thereof" may be achieved by means of a recitation of a representative number of species falling within the scope of the genus or of a recitation of structural features common to the members of the genus, which features constitute a substantial portion of the genus. Regents of the University of California v. Eli Lilly & Co., 119 F3d 1559, 1569, 43 USPQ2d 1398, 1406 (Fed. Cir. 1997). In Regents of the University of California v. Eli Lilly (43 USPQ2d 1398-1412), the court held that a generic statement which defines a genus of nucleic acids by only their functional activity does not provide an adequate written description of the genus. The court indicated that, while applicants are not required to disclose every species encompassed by a genus, the description of the genus is achieved by the recitation of a representative number of species falling within the scope of the claimed genus. At section B (1), the court states “An adequate written description of a DNA ... requires a precise definition, such as by structure, formula, chemical name, or physical properties, not a mere wish or plan for obtaining the claimed chemical invention”.
Hence, an adequate written description of the components requires more than a mere statement that it is part of the invention.
The description requirement of the patent statue requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984).
Accordingly, claiming “lonafarnib or a derivative thereof, or solvates, salts, stereoisomers, complexes, polymorphs, crystalline forms, racemic mixtures, diastereomers, enantiomers, tautomers, isotopically labelled forms, prodrugs, and combinations thereof", in the absence of knowledge as to what Applicant regards as “lonafarnib or a derivative thereof, or solvates, salts, stereoisomers, complexes, polymorphs, crystalline forms, racemic mixtures, diastereomers, enantiomers, tautomers, isotopically labelled forms, prodrugs, and combinations thereof” is not a description of “lonafarnib or a derivative thereof, or solvates, salts, stereoisomers, complexes, polymorphs, crystalline forms, racemic mixtures, diastereomers, enantiomers, tautomers, isotopically labelled forms, prodrugs, and combinations thereof.” Especially of concern are what derivatives, solvates, complexes, polymorphs, crystalline forms, isotopically labelled forms and prodrugs Applicant has contemplated or actually obtained possession of.
In Applicant’s originally filed specification, the recitation of the term “lonafarnib” is found on page 3, paragraph 14 and is described as: “The term “lonafarnib,"” also known under the trade name Sarasar® (Schering), refers to a farnesyltransferase (FTase) inhibitor, 4(2[4-[@1R)-3,10-dibromo-8-chloro-6,11-dihydro- 5Hbenzo[5,6]-cyclohepta[1,2b ]pyridin-11y] ]-piperidino]-2-oxoethyl]-1-piperidinecarboxamide), which has the structure (I) shown below.”
However, there is no examples or description of what Applicant regards as “lonafarnib or a derivative thereof, or solvates, salts, complexes, polymorphs, crystalline forms, isotopically labelled forms, prodrugs, and combinations thereof”. Therefore, Applicant fails to adequately describe as to what Applicant defines or considers “lonafarnib or a derivative thereof”.
As per MPEP 2163, 1, II, 3, i): “Whether the specification shows that the inventor was in possession of the claimed invention is not a single, simple determination, but rather is a factual determination reached by considering a number of factors. Factors to be considered in determining whether there is sufficient evidence of possession include the level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention.
“In contrast, for inventions in emerging and unpredictable technologies, or for inventions characterized by factors not reasonably predictable which are known to one of ordinary skill in the art, more evidence is required to show possession.”
Braga et al.. teaches that solvates, polymorphs and crystalline forms are not predictable in the art: “Crystals containing solvent molecules (solvates) are often formed unpredictably. Whether a given molecule will precipitate out of a solvent, say water, with one or more molecules of water in the unit cell is not foreseeable. In the case of water, sometimes hydrates are formed even upon crystallization from organic solvents…Nor is it predictable whether the hydrate will be more stable or less stable of the corresponding anhydrous forms, or whether other sub- or super-hydrates, let al.one nonstoichiometric hydrates stable over a range of compositions, will be formed. The practical consequences of this “uncertainty principle” are enormous as they impact on the stability, processability, reproducibility, even transport and manufacture conditions, hence on the market potentials, of any chemical species (Braga, Dario, Simone d'Agostino, Elena Dichiarante, Lucia Maini, and Fabrizia Grepioni. "Dealing with crystal forms (the kingdom of serendip?)." Chemistry–An Asian Journal 6, no. 9 (2011): 2214-2223).
Braga further explains “None of the crystal screening methods, however, is yet able to remove the uncertainty related to the possibility of missing an important crystal form and perhaps even the thermodynamically most stable form. This is what makes the quest for crystal forms an exciting task. Each new crystallization process, whether from solvent or melt of vapor, is a travel in an uncharted territory. Despite the intense investigations and large investments, the control over nucleation, crystallization, and composition of a new crystalline phase still represents a substantial scientific challenge. It is still simply not possible to predict whether a given molecule will crystallize from solution in one or many crystal forms (single entity polymorphs), will form solvates with different stoichiometries or will be “happy” to link up with other molecules and form stable cocrystals.”
In a similar manner, prodrugs are also not reasonably predictable.
Ettmayer notes that “The majority of all prodrug approaches face the challenge of identifying the optimal prodrug plus its activation system to enhance or prolong the concentration of the active principle at the site of action. Because of the complex situation of prodrug transport and processing, we recommend, especially for novel prodrug principles, that the first step should be to design and investigate different prodrug prototypes of high diversity (different attachment sites, linkers, promoieties, hydrolytic, oxidative, reductive activation, chemical vs enzymatic activation). The feasibility of these prototypes should subsequently be evaluated with appropriate in vivo pharmacokinetic experiments (Ettmayer, Peter, Gordon L. Amidon, Bernd Clement, and Bernard Testa. "Lessons learned from marketed and investigational prodrugs." Journal of medicinal chemistry 47, no. 10 (2004): 2393-2404).”
Consequently, a prodrug form of a compound of Formula (I) is likewise not predictable and depends on multiple variables, further design and optimization.
In terms of isotopically labelled forms, Applicant has provided no definitions or examples in the specification, nor has Applicant provided any examples demonstrating isotope incorporation as a description of what constitutes “isotopically labelled forms.”
On this basis, a person of ordinary skill in the art would not recognize from the disclosure that the applicant was in possession of a “lonafarnib or a derivative thereof, or solvates, salts, stereoisomers, complexes, polymorphs, crystalline forms, racemic mixtures, diastereomers, enantiomers, tautomers, isotopically labelled forms, prodrugs, and combinations thereof”.
The specification does not clearly allow persons of ordinary skill in the art to recognize that they invented what is claimed (see Vas-Cath at page 1116).
Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. 112 is severable from its enablement provision (see page 1115).
To satisfy the written description requirement, the specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention at the time of filing.
Specifically, the specification must describe the claimed invention in a manner understandable to a person of ordinary skill in the art in a way that shows that the inventor actually invented the claimed invention at the time of filing. Id.; Ariad, 598 F.3d at 1351, 94 USPQ2d at 1172. See MPEP 2163, I
Consequently, the specification does not clearly allow persons of ordinary skill in the art to recognize that Applicant invented what is claimed.
Therefore, Claims 1-11 and 13-15 are rejected on grounds of lacking written description.
Claims 1-11 and 13-15 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 claim(s) contains 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 1-11 are directed towards “A method of treatment or prevention of a viral disease in a subject, comprising a step of administering a compound to the subject, wherein the viral disease is caused by a virus comprising a membrane fusion glycoprotein (F-protein), and wherein the compound is lonafarnib or a derivative thereof, or solvates, salts, stereoisomers, complexes, polymorphs, crystalline forms, racemic mixtures, diastereomers, enantiomers, tautomers, isotopically labelled forms, prodrugs, and combinations thereof.”
Claims 13-15 are directed towards “A method for inhibiting entry of a virus into a host cell, comprising a step of contacting the virus with lonafarnib or a derivative thereof.”
As aforementioned, Applicant has not defined derivatives of lonafarnib.
On page 4, paragraph [19], Applicant defines treatment as: “The terms "treatment", "treating", and "treat" are defined as acting upon a disease, disorder, or condition with an agent to reduce or ameliorate the pharmacologic and/or physiologic effects of the disease, disorder, or condition and/or its symptoms. "Treatment," as used herein, covers any treatment of a disease in a human subject, and includes: (a) reducing the risk of occurrence of the disease in a subject determined to be predisposed to the disease but not yet diagnosed as infected with the disease, (b) impeding the development of the disease, and/or (c) relieving the disease, i.e., causing regression of the disease and/or relieving one or more disease symptoms. "Treatment" is also meant to encompass delivery of an inhibiting agent to provide a pharmacologic effect, even in the absence of a disease or condition. For example, "treatment" encompasses delivery of a disease or pathogen inhibiting agent that provides for enhanced or desirable effects in the subject (e.g., reduction of pathogen viral load, reduction of disease symptoms, etc.).”
No definition is provided for prevention; therefore, prevention is defined based on what is commonly known in the art.
No specific definition is provided for subject; however, Applicant has described preferred subject on page 5, paragraph 23 as “children between 0 and 10 years of age; Elderly of 50 years of age or older; and Immunosuppressed patients.”
On page 4, paragraph 20, Applicant defines that “The virus in accordance with the present invention is preferably an enveloped virus. Such viruses can be selected from the group of orthopneumoviruses, and preferably is a human respiratory syncytial virus (HRSV). Such HRSV strains according to the invention may be HRSV-A or HRSV-B.”
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).”
On pages 4-5, paragraph 21, Applicant defines “A “disease” in context of the present invention means any disease caused, directly or indirectly, by an infection with a virus, such as HRSV, as well as diseases or conditions which predispose a patient to infection by a virus, such as HRSV. Examples of diseases falling into the former category include pneumonia and bronchiolitis. Diseases and conditions in the latter category (i.e., those which place the patient at risk of severe viral infection, in particular HRSV infection) include cystic fibrosis, congenital heart disease, cancer, age-related immunosuppression, transplant recipients and, generally, any condition that causes a state of immunosuppression or decreased function of the immune system such as postoperative organ transplantation regimens or premature birth.”
In summary, it is reasonable to conclude that the claims are broad with respect to the viral disease, virus, compound, 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 methods for preventing or treating a viral disease in a subject comprising administering lonafarnib or a derivative thereof.
However, there are no known antivirals present in the art capable of treating and preventing all viruses and viral diseases in all humans. In fact, many viruses do not have treatment or prevention options.
By example only, Torresi teach several viruses with no vaccines or treatment options whose preventive measures are non-pharmacological as described below (Torresi J, McGuinness S, Leder K, O’Brien D, Ruff T, Starr M, Gibney K. Non-vaccine-Preventable Infections. Manual of Travel Medicine. 2019 Oct 19:225–64. doi: 10.1007/978-981-13-7252-0_5. PMCID: PMC7120392).
“Chikungunya virus has long been known to be endemic in tropical Africa and Asia. The virus is present throughout much of Africa, with transmission thought to occur mainly between mosquitoes and monkeys… There are no specific treatments for Chikungunya virus infection… The only way to prevent infection is to avoid mosquito bites as there is no vaccine currently available.”
“ Dengue Fever… Caused by a flavivirus with four serotypes (DEN 1, DEN 2, DEN 3 and DEN 4)… Dengue is transmitted by the bite of the Aedes mosquito (Aedes aegypti and Aedes albopictus)… The only way to prevent infection in travelers is to avoid mosquito bites.”
“Hepatitis C virus (HCV) of which there are six main genotypes…A vaccine for HCV is not available, and immunoglobulin has not been shown to be effective in preventing infection. Prevention is therefore based on avoiding activities that are associated with potential exposure to blood or body fluids. In general, travelers should follow similar advice as for the prevention of HIV infection:”
“MERS is a respiratory infection caused by a coronavirus, called MERS. No specific therapy for MERS exists; treatment is supportive and based on the patient’s clinical condition. No vaccine is currently available.”
“Zika virus (ZIKV), a flavivirus… There is no vaccine for Zika virus. All travelers to Zika endemic areas should be advised to avoid being bitten by mosquitoes and be counselled on measures to prevent sexual and vertical transmission.”
As additional examples for respiratory viruses, 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).”
Boncristiani more specifically teaches 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.”
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.”
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.”
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.”
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.”
Therefore, it is not reasonable to conclude that lonafarnib and any derivative of lonafarnib would be predicted to generally treat and prevent all viruses and viral diseases as claimed based on the broad definition of “treating” and “preventing.”
In terms of claims 13-15, inhibiting entry of a virus into a host cell is selective to the virus; therefore, it is not reasonable to claim lonafarnib and its derivatives would be selective towards inhibiting viral entry into all host cells as claimed.
Liu explains that “Pharmacological interference with these structural changes is an attractive antiviral strategy to prevent the delivery of the viral genome and, hence, to block the infection prior to the onset of viral gene expression and replication. The complex mechanisms regulating the time and place of the fusion reaction reflect the importance of this step in viral infection and its potential as an antiviral target (Liu, H.Y. and Yang, P.L., 2021. Small-molecule inhibition of viral fusion glycoproteins. Annual review of virology, 8(1), pp.459-489).”
Liu further explains “Although contemporary drug discovery efforts have been successful in developing direct-acting antivirals targeting viral enzymes, there are currently no approved small-molecule drugs that target viral GPs. This is because enzymes have active sites that have evolved naturally to bind small molecules and to catalyze formation or scission of distinct covalent bonds. These characteristics enable rational, structure- and mechanism-based inhibitor design and medicinal chemistry. By contrast, viral fusion proteins lack classical active sites and catalyze a process driven by the formation and disruption of multiple noncovalent interactions. Consequently, potential target sites for small molecules that could block fusogenic activity are generally not obvious even in high-resolution structures of viral fusion proteins.”
Liu further explains that “Despite this fundamental challenge, there are increasing examples of small molecules that exert antiviral activity by binding to a viral fusion protein specifically and inhibiting the structural changes that are coupled to membrane fusion during viral entry. These successes have come from a variety of approaches, including (a) high-throughput screens utilizing recombinant proteins and peptides engineered to mimic specific structural changes that accompany membrane fusion; (b) in silico screens utilizing computational docking to identify potential ligands, subsequently validated in biochemical and virological experiments; and (c) unbiased phenotypic screens for compounds with antiviral activity, which have serendipitously yielded compounds that inhibit viral fusion. Careful characterization of the binding sites and mechanisms of these small molecules has led to pharmacological validation of discrete structural targets within viral fusion proteins. This foundational work has been essential for the medicinal chemistry optimization necessary to advance these compounds toward the clinic.”
Liu further explains that “The development of small molecules targeting viral fusion proteins as antiviral drugs has lagged behind the development of other classes of direct-acting antivirals, most notably those targeting viral enzymes. This is partly due to the inherent challenges of applying rational, structure-based drug discovery and optimization approaches to this target class. A second challenge has been the diversity of viral fusion proteins and their structural tolerance of mutations to escape immune pressure. This raises legitimate concerns that a limited spectrum of activity and poor resistance profile would render viral fusion protein inhibitors of limited use as therapeutics.”
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, virology, and pharmacology. One of ordinary skill would be a person with training in medicine, virology, 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 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.
Additionally, there are constantly new viruses that continue to emerge.
There is to date no general pharmacological agent known to treat and prevent all viruses known in addition to viruses that are unknown or challenging to diagnose.
Based on these cumulative factors, it is reasonable to conclude that predictability in the art is extremely 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:
Screening of ReFRAME Drug bank against HEp2 cells infected with HRSV-A.
Comparative studies with lonafarnib and tipifarnib in HRSV infected cells for inhibition efficiency and mechanism of action (in vitro, HRSV-A and HRSV-B).
Applicant has failed to provide working examples and key details encompassing the diverse range of viruses and subjects claimed, including providing working examples representative for the diversity of viruses, patient populations, and goal of virus treatment and prevention.
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.
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 that lonafarnib and its derivatives can treat and/prevent viruses and inhibit entry into host cells encompassing the diversity of viruses, viral diseases, subjects and host cells claimed. Applicant has only studied HRSV using in vitro cell lines, which are limited in translation across subjects claimed, specific patient populations, and viral diseases claimed.
Long-term studies supporting lonafarnib and its derivatives can prevent the viruses and viral diseases as claimed. As aforementioned, many viruses are not preventable via pharmacological means.
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 1-11, and 13-15.
Therefore, Claims 1-11 and 13-15 are rejected for lacking enablement.
Claim Rejections - 35 USC § 112(b)
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, 5, 6 7, 9, 10, 11, and 14 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claim 1 , the parentheses for the phrase “membrane fusion glycoprotein (F-protein)” renders the claim indefinite because it is unclear whether the limitation within the parentheses are part of the claimed invention. See MPEP § 2173.05(d).
Claims 5, 6, 7, 9, 10, and 11 are likewise rejected for failing to remedy this ambiguity.
Claim 7 contains the trademark/trade names “Ziresovir” and “Lumicitabine”. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe the source of the antiviral compound and, accordingly, the identification/description is indefinite.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c).
In the present instance, claim 7 recites the broad recitation “ribavirin, Palivizumab, MK-1654, MEDI8897, JNJ-53718678, Ziresovir, RV521, Lumicitabine and EDP-938” and the claim also recites “preferably is Palivizumab” which is the narrower statement of the range/limitation.
In a similar fashion, claim 10 recites the broad recitation “ wherein the viral disease is not treatable by inhibition of a farnesyltransferase” and the claim also recites “preferably wherein the viral disease is not hepatitis D and Severe Acute Respiratory Syndrome (SARS), such as SARS-CoV2.”
Likewise claim 14, recites the broad recitation “wherein the virus comprises a F-protein” and the claim also recites “preferably an F-protein comprising an amino acid sequence that is at least 80% identical to a sequence shown in any of SEQ ID NO: 1 to 3.”
The claims are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Applicant is furthermore reminded as per MPEP 2173.05(d): “Description of examples or preferences is properly set forth in the specification rather than the claims. If stated in the claims, examples and preferences may lead to confusion over the intended scope of a claim.”
Regarding claim 10, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claim 11 , the phrase "for example" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim 13 is rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Cory et al (WO 2011/088126, Information Disclosure Statement, Foreign Patent Document No. 1).
Regarding claim 13, Cory teaches “A method for inhibiting entry of a virus into a host cell, comprising a step of contacting the virus with lonafarnib or a derivative thereof.”
Claim 18 of Cory specifically teaches “A method of inhibiting hepatitis D virus proliferation in a cell comprising contacting the cell comprising the hepatitis D virus with an effective amount of EBP921 or EBP994 or a metabolite or salt of each thereof, thereby inhibiting the hepatitis D virus proliferation in the cell.”
Page 3, paragraph 2, lines 12-13 of Cory teaches that EBP994 is also known as lonafarnib.
As per MPEP 2112.02, II: The discovery of a new use for an old structure based on unknown properties of the structure might be patentable to the discoverer as a process of using. In re Hack, 245 F.2d 246, 248, 114 USPQ 161, 163 (CCPA 1957). However, when the claim recites using an old composition or structure and the "use" is directed to a result or property of that composition or structure, then the claim is anticipated. In re May, 574 F.2d 1082, 1090, 197 USPQ 601, 607 (CCPA 1978).”
Both Cory and instant invention involve contacting lonafarnib with the virus in a host cell. Cory’s claim additional uses the transitional word “comprising,” indicting that additional process steps and/or elements can be included (MPEP 2111.03, I).
Therefore, Cory’s claims directed towards inhibiting virus proliferation are inclusive of inhibiting entry of a virus as the identical compounds are used, identical chemical compounds cannot have mutually exclusive properties (MPEP 2112.01, II), and the claim is inclusive of additional process steps or elements.
Therefore, claim 13 is anticipated by Cory.
Conclusion
Claims 1-11 and 13-15 are under consideration and are rejected.
No claims allowed.
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/C.L.L./Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622