DETAILED ACTION
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 .
The amendments and remarks filed 12/18/25 are acknowledged. Claims 54,57, 59, 61, and 73 have been amended. Claims 74-76 have been added. Claims 1-53, 60, and 62 have been canceled. Claims 54-59, 61, 63-76 are pending and under examination.
Withdrawn Rejections
The rejection of claims 60 and 62 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or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention, is withdrawn in light of Applicant’s amendment thereto. See page 2 of the previous Office action.
The rejection of claims 54, 56, 59, 61, 63-65, 69-71, and 73 under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Blatt (US Patent Application Publication 2005/0002901 A1, published, January 6, 2005), is withdrawn in light of Applicant’s amendment thereto. See paragraph 6, page 3 of the previous Office action.
New Rejections
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 54-59, 61, and 63-76 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.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed. The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the application. These include “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.”
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, disclosure of drawings, or by disclosure of relevant identifying characteristics, for example, structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the Applicants were in possession of the claimed genus.
The instant claims are drawn to a method of treating a subject, the method comprising subcutaneously administering to the subject a therapeutically effective amount of interferon lambda, wherein the subject has an infection caused by a coronavirus or has been exposed to the coronavirus, and wherein the subject is one or more of: a subject over 55 years of age a subject with a chronic medical condition who may be at risk for severe illness a subject with an underlying medical comorbidity: and/or or a subject with a persistent coronavirus infection, wherein the persistent coronavirus infection is a coronavirus infection lasting longer than an acute coronavirus infection.
Claim 73 is drawn to a method of preventing or reducing incidence of a coronavirus infection in a subject exposed to coronavirus, the method comprising subcutaneously administering to the subject a therapeutically effective amount of interferon lambda, wherein the subject is one or more of: a subject over 55 years of age; a subject with a chronic medical condition who may be at risk for severe illness; and/or a subject with an underlying medical comorbidity.
The specification teaches that the term “interferon-lambda” or “IFN-λ” as used herein includes naturally occurring IFN-λ; synthetic IFN-λ; derivatized IFN-λ (e.g., PEGylated IFN-λ, glycosylated IFN-λ, and the like); and analogs of naturally occurring or synthetic IFN-λ. In some embodiments, an IFN-λ is a derivative of IFN-λ that is derivatized (e.g., chemically modified relative to the naturally occurring peptide) to alter certain properties such as serum half-life. As such, the term “IFN-λ” includes IFN-λ derivatized with polyethylene glycol (“PEGylated IFN-λ”), and the like.
Although the claims are inclusive of methods of treating coronavirus comprising administering pegylated IFN lambda, the claims are not limited to these species, and broadly encompass naturally occurring IFN-λ, synthetic IFN-λ, derivatized IFN-λ (e.g., glycosylated IFN-λ, and the like) and analogs of naturally occurring or synthetic IFN-λ. These IFN lambdas must be able to treat coronavirus infection. The encompassed interferon lambdas have no correlation between their structure and function. The specification provides no guidance regarding which IFN-λ species (i.e., naturally-occurring, synthetic, derivatized, glycosylated, or analogs of naturally occurring or synthetic IFN-λ) is capable of the claimed function, and the single species does not sufficiently represent the vast breadth of the encompassed genus of proteins. Therefore, the specification provides insufficient written description to support the genus encompassed by the claim. Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear 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 is, for purposes of the 'written description' inquiry, whatever is now claimed." (See page 1117.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116.)
With the exception of treating administering the interferon lambda set forth in SEQ ID NO: 1 for treating a subject who has an infection caused by a coronavirus, the skilled artisan cannot envision the detailed chemical structure of the encompassed proteins, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it. The nucleic acid and/or protein itself is required. See Fiers v. Revel, 25 USPQ2d 1601,1606 (CAFC 1993) and Amgen Inc. V. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. In Fiddes v. Baird, 30 USPQ2d 1481,1483, claims directed to mammalian FGF's were found unpatentable due to lack of written description for the broad class. The specification provided only the bovine sequence.
University of California v. Eli Lilly and Co., 43 USPQ2d 1398, 1404. 1405 held that: ...To fulfill the written description requirement, a patent specification must describe an invention and does so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines Inc., 107 F.3d 1565, 1572, 41 USPQ2dl961,1966 (1997); In re Gosteli, 872 F.2dl008,1012,10 USPQ2dl614, 1618 (Fed. Cir. 1989) (" [T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed."). Thus, an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious," and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2d.
The use of interferon-λ in the context of viral infection is discussed by Hermant et al. (J Innate Immun 2014;6:563–574). Hermant et al. teach that one of the first studies reporting IFNλ antiviral activity in vivo demonstrated that intravaginal treatment of female mice with IFNλ prior to infection with herpes simplex virus-2 prevented virus replication in the vaginal mucosa (See page 564). Hermant et al. teach that using IFNλ receptor deficient mice, it was shown that the contribution of IFNλ to the control of viral infection greatly varied according the virus (See page 564 and table 1). For instance, studies showed no protective effect of IFNλ against infection with encephalomyocarditis virus, lymphocytic choriomeningitis virus, or vesicular stomatitis virus (See page 564). Similarly, no antiviral activity of IFNλ could be detected in mice against hepatotropic viruses, such as Rift Vallet fever, Lassa fever virus, or mutant strain of Thogoto virus (See page 564). IFNλ was found to have a modest but detectable antiviral activity in vivo against influenza virus, human metapneumovirus and severe acute respiratory syndrome coronavirus (See page 564). Additional studies carried out with influenza virus showed variable extents of protection mediated by IFNλ (See page 564). Hermant et al. teach that the contribution of IFNλ was much clearer in respiratory syncytial virus and IFNλ was shown to play a major role in the protection against rotavirus (See page 564). Thus, the antiviral activity of IFNλ depends on the virus, and it cannot be predicted if a particular IFNλ species would be effective against coronavirus. The art supports that one of skill in the art would need guidance regarding the specific IFNλ can be used for treating coronavirus.
The claims are not limited to a specific IFNλ, and broadly encompass any possible IFNλ protein. However, protein chemistry is probably one of the most unpredictable areas of biotechnology. Consequently, the effects of sequence dissimilarities upon protein structure and function cannot be predicted. Punta et al. (PLoS Comput Biol 4(10): e1000160, 2008) teach that homology (both orthology and paralogy) does not guarantee conservation of function (See page 2). Punta et al. teach that relatively small difference in sequence can sometimes cause quite radical changes in functional properties, such as a change of enzymatic action, or even loss or acquisition of enzymatic activity itself (See page 2). Punta et al. teach that it is also apparent that there is no sequence similarity threshold that guarantees that two proteins share the same function (see page 2). Punta et al. teach that homology between two proteins does not guarantee that they have the same function, not even when sequence similarity is very high (including 100% sequence identity) (See page 2 and table 2). Punta et al. teach that proteins live and function in 3D, and therefore structural information is very helpful for predicating function (See page 4). However, as with sequence, two proteins having the same overall architecture, and even conserved functional residues, can have unrelated functions (See page 4). Punta et al. teach that still; structural knowledge is an extremely powerful tool for computational function prediction (See page 5).
Similarly, Whisstock et al. (Quarterly Reviews in Biophysics. 36(3):307-340, 2007) teach that the prediction of protein function from sequence and structure is a difficult problem (See abstract). Although many families of proteins contain homologues with the same function, homologous proteins often have different functions as the sequences progressively diverge (See page 309). Whisstock et al. teach that moreover, even closely related proteins can change function, either through divergence to a related function or by recruitment for a very different function (See page 309). Further, Whisstock et al. note that in some instances, even sequences that are the same can have different functions. For example, eye lens proteins in the suck are identical in sequence to active lactate dehydrogenase and enolase in other tissues, although they do not encounter the substrates in the eye (See page 310). Whisstock et al. teach that assigning a function to an amino acid sequence based upon similarity becomes significantly more complex as the similarity between the sequence and a putative homologue fall (See page 321). Whisstock et al. teach that while it is hopeful that similar proteins will share similar functions, substitution of a single, critically placed amino acid in an active-site may be sufficient to alter a protein’s role fundamentally (See pages 321-323).
The sensitivity of proteins to alterations of even a single amino acid in a sequence are exemplified by Burgess et al. (J. Cell Biol. 111:2129-2138, 1990) who teach that replacement of a single lysine reside at position 118 of acidic fibroblast growth factor by glutamic acid led to the substantial loss of heparin binding, receptor binding and biological activity of the protein and by Song et al. (Molecular Biology of the Cell, 15:1287–1296, March 2004) who teach that substitution of alanine for aspartate in survivin results in the conversion of survivins’ apoptotic function from anti-apoptotic to proapoptotic and changes in its subcellular localization (See page 1287-1289). Moreover, Defeo-Jones et al. (Molecular and Cellular Biology, Sept. 1989, p. 4083-4086) teach that the conservative substitution of lysine for arginine at position 42 completely eliminated biological activity (See abstract and pages 4084-4085). These references demonstrate that even a single amino acid substitution will often dramatically affect the biological activity and characteristics of a protein.
Additionally, Bork (Genome Research, 2000; 10:398-400) clearly teaches the pitfalls associated with comparative sequence analysis for predicting protein function because of the known error margins for high-throughput computational methods. Bork specifically teaches that computational sequence analysis is far from perfect, despite the fact that sequencing itself is highly automated and accurate (p. 398, column 1). One of the reasons for the inaccuracy is that the quality of data in public sequence databases is still insufficient. This is particularly true for data on protein function. Protein function is context dependent, and both molecular and cellular aspects have to be considered (p. 398, column 2). Conclusions from the comparison analysis are often stretched with regard to protein products (p. 398, column 3). Further, although gene annotation via sequence database searches is already a routine job, even here the error rate is considerable (p. 399, column 2). Most features predicted with an accuracy of greater than 70% are of structural nature and, at best, only indirectly imply a certain functionality (see legend for table 1, page 399). As more sequences are added and as errors accumulate and propagate it becomes more difficult to infer correct function from the many possibilities revealed by database search (p. 399, paragraph bridging columns 2 and 3). The reference finally cautions that although the current methods seem to capture important features and explain general trends, 30% of those features are missing or predicted wrongly. This has to be kept in mind when processing the results further (p. 400, paragraph bridging cols 1 and 2). Given not only the teachings of these references that point out the limitations and pitfalls of using sequence to predict functions, and the lack of representative number species across the breadth of the genus, one of skill in the art would not reasonably conclude that the full breadth of the claims meets the written description provision of 35 USC 112a).
MPEP § 2163.02 states, “[a]n objective standard for determining compliance with the written description requirement is, ‘does the description clearly allow person of ordinary skill in the art to recognize that he or she invented what is claimed’”. The courts have decided: the purpose of the “written description" requirement is broader than to merely explain how to "make and use"; the 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 is for purposes of the “written description” inquiry, whatever is now claimed. See Vas-Cath, Inc v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Federal Circuit, 1991).
Furthermore, the written description provision of 35 USC §112 is severable from its enablement provision; and adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it. Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993). And Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. Moreover, an adequate written description of the claimed invention must include sufficient description of at least a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics sufficient to show that Applicant was in possession of the claimed genus. However, factual evidence of an actual reduction to practice has not been disclosed by Applicant in the specification; nor has Applicant shown the invention was “ready for patenting” by disclosure of drawings or structural chemical formulas that show that the invention was complete; nor has the Applicant described distinguishing identifying characteristics sufficient to show that Applicant were in possession of the claimed invention at the time the application was filed.
Therefore, for all these reasons the specification lacks adequate written description, and one of skill in the art cannot reasonably conclude that Applicant had possession of the claimed invention at the time the instant application was filed.
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(s) 54-55, 59, 63-65, 67-68, 71, 73-74, and 76 is/are rejected under 35 U.S.C. 103 as being unpatentable over Blatt (US Patent Application Publication 2005/0002901 A1, published, January 6, 2005) in view of Gorse et al. (The Journal of Infectious Diseases 2009; 199:847–57) and Alder (2020, February 5). Why Coronaviruses Hit Older Adults Hardest. https://cdn.ymaws.com/www.servicecoordinator.org/resource/resmgr/images/misc_/coronavirus_2020/aarp_why_coronaviruses_hit_o.pdf).
Blatt teaches a method of treating a coronavirus infection comprising administering to an individual a type III interferon receptor agonist in an amount effective to ameliorate the clinical course of the disease (See paragraphs 0007 and 0037). Blatt teaches that the type III interferon is an IL-28a, IL-28b, or IL-29. (See paragraph 0142). It should be noted that interferon lambda-3 is also known as IL-28 and interferon lambda-1 is also known as IL-29. Blatt teaches that the type III interferon is administered subcutaneously (See paragraph 0010). Blatt et al. teach that the interferon therapy is initiated after the appearance of clinical signs of SARS, e.g., the appearance of a fever often exceeding 38oC, and the advantage of the method is the severity of SARS symptoms is reduced, e.g., the viral load is reduced, and/or the time to viral clearance is reduced, and/or the morbidity or mortality is reduced (See paragraphs 0043 and 0065). Blatt et al. teach that the interferon therapy is begun from about 4 days to about 7 days, and from about 7 days to about 10 days following exposure to the coronavirus (See paragraph 0053). Blatt et al. teach that the method involves administering an interferon treatment more than 72 hours, 4 days, 5 days, 6 days, or 7 days after appearance of a symptom of SARS (See paragraph 0065). Blatt teaches that the treatment is a newly diagnosed infection (e.g., treatment is initiated after the appearance of clinical symptoms of SARS, e.g., the appearance of a fever often exceeding 38° C)) (See paragraph 0043). Blatt teaches that the dose of the type III interferon ranges from about 1 μg to about 300 μg. Blatt teaches that a Type I or Type III interferon receptor agonist and/or a Type II interferon receptor agonist can be administered twice daily, daily, three times a week, twice a week, weekly, or twice a month for a period of one week to about 16 weeks (See paragraphs 0052 and 0189). Blatt teaches that the interferon treatments can be used in conjunction with administration of an additional antiviral agents (See paragraph 0208).
Blatt does not teach wherein the subject is at least 55 years old; wherein the subject has at least one of a pneumonia, fever, shortness of breath, cough, myalgia, fatigue, sore throat, sputum production, headache, hemoptysis, diarrhea, leukopenia, leukocytosis, lymphopenia, elevated alanine aminotransferase, or elevated aspartate aminotransferase levels.
Gorse et al. teach that HCoV infection has been viewed as a contributor to exacerbations of underlying chronic obstructive pulmonary disease (COPD), asthma, congestive heart failure, and severe illnesses requiring emergency care and hospitalization of patients with chronic medical conditions (See page 847). Gorse et al. teach that HCoV infections were clinically significant in patients ≥ 50 years of age with COPD and other illnesses (See page 852). Gorse et al. teach that the chronic other illnesses include diabetes mellitus and heart disease (See page 852 and table 3). Gorse et al. teach that more than 8-% of the HCoV-associated infections were characterized by new or increased cough, sputum production, nasal congestion, and fatigue and/or malaise (See page 853 and table 4).
Adler teaches that 2019-nCoV is a novel coronavirus on the rise and teaches that older adults may be particularly susceptible to respiratory illness, which can cause pneumonia and symptoms like fever, cough, and shortness of breath (See page 1). It should be noted that SARS-CoV-2 is the virus that causes 2019-nCoV. Alder teaches that people who are at higher risk for severe disease and death are those who are older and with underlying health conditions (See page 1). Alder teaches that the disease is more lethal in people over the age of 50 (See page 1).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Blatt to specifically treat patients at least 55 years old with a chronic medical condition because Gorse et al. and Alder teach that coronavirus infections and its associated illnesses are more severe in people over the age of 50. One of ordinary skill in the art would be motivated, and with a reasonable expectation of success, to treat people over the age of 50 who have a pre-existing condition according to the method of Blatt because doing so would reduce the severity of disease in a population that is at a higher risk for severe disease and death.
Regarding claims 67-68, Blatt does not teach the interferon lambda is administered at a dose of 180 mcg per week, or at 90 micrograms twice per week, or 80 mcg twice per week, or 180 mcg per week; wherein the interferon lambda is administered at a dose of 120 mcg once a week, 60 mcg twice per week, or 70 mcg twice per week, or 120 mcg per week.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to optimize of the dose of the interferon lambda. Blatt teaches a dose range that encompasses the doses recited in the instant claims. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). Further, the art recognizes the dose as a result-effective variable that can be optimized, and thus the optimal dose of the interferon lambda could be determined by one of skill in the art through routine experimentation. Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)
Claim(s) 57-58, 72, and 75 is/are rejected under 35 U.S.C. 103 as being unpatentable over Blatt (US Patent Application Publication 2005/0002901 A1, published, January 6, 2005) in view of Gorse et al. (The Journal of Infectious Diseases 2009; 199:847–57) and Alder (2020, February 5). Why Coronaviruses Hit Older Adults Hardest. https://cdn.ymaws.com/www.servicecoordinator.org/resource/resmgr/images/misc_/coronavirus_2020/aarp_why_coronaviruses_hit_o.pdf), as applied to claims 54-55, 59, 63-65, 67-68, 71, 73-74, and 76 above, and further in view of Klucher et al. (US Patent Application 20050244423 A1, published November 3, 2005)
Blatt teaches a method of treating a coronavirus infection comprising administering to an individual a type III interferon receptor agonist in an amount effective to ameliorate the clinical course of the disease (See paragraphs 0007 and 0037). Blatt teaches that the type III interferon is an IL-28a, IL-28b, or IL-29. (See paragraph 0142). It should be noted that interferon lambda-3 is also known as IL-28 and interferon lambda-1 is also known as IL-29. Blatt teaches that the type III interferon is administered subcutaneously (See paragraph 0010). Blatt et al. teach that the interferon therapy is initiated after the appearance of clinical signs of SARS, e.g., the appearance of a fever often exceeding 38oC, and the advantage of the method is the severity of SARS symptoms is reduced, e.g., the viral load is reduced, and/or the time to viral clearance is reduced, and/or the morbidity or mortality is reduced (See paragraphs 0043 and 0065). Blatt et al. teach that the interferon therapy is begun from about 4 days to about 7 days, and from about 7 days to about 10 days following exposure to the coronavirus (See paragraph 0053). Blatt et al. teach that the method involves administering an interferon treatment more than 72 hours, 4 days, 5 days, 6 days, or 7 days after appearance of a symptom of SARS (See paragraph 0065). Blatt teaches that the treatment is a newly diagnosed infection (e.g., treatment is initiated after the appearance of clinical symptoms of SARS, e.g., the appearance of a fever often exceeding 38° C)) (See paragraph 0043). Blatt teaches that the dose of the type III interferon ranges from about 1 μg to about 300 μg. Blatt teaches that a Type I or Type III interferon receptor agonist and/or a Type II interferon receptor agonist can be administered twice daily, daily, three times a week, twice a week, weekly, or twice a month for a period of one week to about 16 weeks (See paragraphs 0052 and 0189). Blatt teaches that the interferon treatments can be used in conjunction with administration of an additional antiviral agents (See paragraph 0208).
Blatt does not teach wherein the subject is at least 55 years old; wherein the subject has at least one of a pneumonia, fever, shortness of breath, cough, myalgia, fatigue, sore throat, sputum production, headache, hemoptysis, diarrhea, leukopenia, leukocytosis, lymphopenia, elevated alanine aminotransferase, or elevated aspartate aminotransferase levels; wherein the antiviral comprises one or more of remdesivir, chloroquine, tenofovir, or a protease inhibitor.
Gorse et al. teach that HCoV infection has been viewed as a contributor to exacerbations of underlying chronic obstructive pulmonary disease (COPD), asthma, congestive heart failure, and severe illnesses requiring emergency care and hospitalization of patients with chronic medical conditions (See page 847). Gorse et al. teach that HCoV infections were clinically significant in patients ≥ 50 years of age with COPD and other illnesses (See page 852). Gorse et al. teach that the chronic other illnesses include diabetes mellitus and heart disease (See page 852 and table 3). Gorse et al. teach that more than 8-% of the HCoV-associated infections were characterized by new or increased cough, sputum production, nasal congestion, and fatigue and/or malaise (See page 853 and table 4).
Adler teaches that 2019-nCoV is a novel coronavirus on the rise and teaches that older adults may be particularly susceptible to respiratory illness, which can cause pneumonia and symptoms like fever, cough, and shortness of breath (See page 1). It should be noted that SARS-CoV-2 is the virus that causes 2019-nCoV. Alder teaches that people who are at higher risk for severe disease and death are those who are older and with underlying health conditions (See page 1). Alder teaches that the disease is more lethal in people over the age of 50 (See page 1).
Blatt, Gorse, and Adler do not teach wherein the interferon is pegylated interferon lambda or pegylated interferon lambda-1a; wherein the antiviral comprises one or more of remdesivir, chloroquine, tenofovir, or a protease inhibitor.
Klucher et al. teach a method for treating viral infection comprising administering pegylated IL-28a, IL-29, and IL-28b (See paragraphs 0032-0035 and 0065 and claims 3-9). It should be noted that interferon lambda-3 is also known as IL-28 and interferon lambda-1 is also known as IL-29. Klucher et al. teach that the viral infection is Coronavirus (causes Severe Acute Respiratory Syndrome (SARS)) (See paragraphs 0142 and 0156 and claim 3). Klucher et al. teach that the polypeptide can be administered subcutaneously (See paragraph 00360-0037). Klucher et al. teach that the polypeptide can be used to treat acute viral infections (See paragraph 0156). Klucher et al. teach that the polypeptide can be administered in combination with another antiviral agent, such as a protease inhibitor (See paragraphs 0139 and 0156). Klucher et al. teach that conjugating the IL28 or IL29 polypeptide to water-soluble polymer moieties, such as PEG, has been shown to enhance the circulating half-life of the interferon, and reduce the immunogenicity of the polypeptide (See paragraph 0065-0071).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Blatt, Gorse, and Adler by substituting pegylated interferon lambda-1a, as taught by Klucher et al., for the interferon lambda because the Klucher et al. teach that the pegylated interferon offers the advantage of a longer half-life and reduced immunogenicity. One of ordinary skill in the art would be motivated to treat a coronavirus infection with pegylated interferon lambda, and with a reasonable expectation of success, because doing so would provide a treatment for coronavirus that has an extended half-life and reduced immunogenicity.
Furthermore, the Supreme Court set forth in KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), that if the prior art contained a method which differed from the claimed method by the substitution of some component with another component, where both components are known in the art, and one of ordinary skill in the art could have substituted one known element for another to yield predictable results, the substitution of one known element for another would have been obvious. The method of Blatt, Gorse, and Adler administers interferon lambda for treating a coronavirus infection. It would be predictable that the pegylated interferon lambda of Klucher et al. could be used in the combined method of Blatt, Gorse, and Adler, since Klucher et al. teach that the pegylated interferon lambda-1a can also be used for treating coronavirus infection. The substitution of the interferon lambda for the pegylated interferon lambda would require no alterations to the polypeptide and the method would still function in the same manner for treating a coronavirus infection. Thus, the combination of prior art references as combined provided a prima facie case of obviousness, absent convincing evidence to the contrary.
Regarding claim 72, Klucher et al. teach that the polypeptide can be administered in combination with another antiviral agent, such as a protease inhibitor (See paragraphs 0139 and 0156).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Blatt, Gorse, and Adler by additionally administering a protease inhibitor because Klucher et al. teach that pegylated pegylated IL-28a, IL-29, and IL-28b can be administered in combination with a protease inhibitor when treating coronavirus. One would have been motivated to combine the agents because each of the therapies has been individually taught in the prior art to be useful for treating coronavirus. Moreover, the instant situation is amenable to the type of analysis set forth in In re Kerkhoven, 205 USPQ 1069 (CCPA 1980) wherein the court held that it is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the very same purpose. The idea of combining them flows logically from having been individually taught in the prior art. Applying the same logic to the instant claims, one of ordinary skill in the art would have been imbued with at least a reasonable expectation of success that by administering pegylated interferon lambda as taught in Blatt, Gorse, and Adler in combination with the a protease inhibitor as taught in Klucher et al., one would achieve a method for treating coronavirus infection.
Claim(s) 66 is/are rejected under 35 U.S.C. 103 as being unpatentable over Blatt (US Patent Application Publication 2005/0002901 A1, published, January 6, 2005) in view of Gorse et al. (The Journal of Infectious Diseases 2009; 199:847–57) and Alder (2020, February 5). Why Coronaviruses Hit Older Adults Hardest. https://cdn.ymaws.com/www.servicecoordinator.org/resource/resmgr/images/misc_/coronavirus_2020/aarp_why_coronaviruses_hit_o.pdf), as applied to claims 54-55, 59, 63-65, 67-68, 71, 73-74, and 76 above, and further in view of Pan et al. (Lancet Infect Dis. 2020 Feb 24;20(4):411–412).
Blatt teaches a method of treating a coronavirus infection comprising administering to an individual a type III interferon receptor agonist in an amount effective to ameliorate the clinical course of the disease (See paragraphs 0007 and 0037). Blatt teaches that the type III interferon is an IL-28a, IL-28b, or IL-29. (See paragraph 0142). It should be noted that interferon lambda-3 is also known as IL-28 and interferon lambda-1 is also known as IL-29. Blatt teaches that the type III interferon is administered subcutaneously (See paragraph 0010). Blatt et al. teach that the interferon therapy is initiated after the appearance of clinical signs of SARS, e.g., the appearance of a fever often exceeding 38oC, and the advantage of the method is the severity of SARS symptoms is reduced, e.g., the viral load is reduced, and/or the time to viral clearance is reduced, and/or the morbidity or mortality is reduced (See paragraphs 0043 and 0065). Blatt et al. teach that the interferon therapy is begun from about 4 days to about 7 days, and from about 7 days to about 10 days following exposure to the coronavirus (See paragraph 0053). Blatt et al. teach that the method involves administering an interferon treatment more than 72 hours, 4 days, 5 days, 6 days, or 7 days after appearance of a symptom of SARS (See paragraph 0065). Blatt teaches that the treatment is a newly diagnosed infection (e.g., treatment is initiated after the appearance of clinical symptoms of SARS, e.g., the appearance of a fever often exceeding 38° C)) (See paragraph 0043). Blatt teaches that the dose of the type III interferon ranges from about 1 μg to about 300 μg. Blatt teaches that a Type I or Type III interferon receptor agonist and/or a Type II interferon receptor agonist can be administered twice daily, daily, three times a week, twice a week, weekly, or twice a month for a period of one week to about 16 weeks (See paragraphs 0052 and 0189). Blatt teaches that the interferon treatments can be used in conjunction with administration of an additional antiviral agents (See paragraph 0208).
Blatt does not teach wherein the subject is at least 55 years old; wherein the subject has at least one of a pneumonia, fever, shortness of breath, cough, myalgia, fatigue, sore throat, sputum production, headache, hemoptysis, diarrhea, leukopenia, leukocytosis, lymphopenia, elevated alanine aminotransferase, or elevated aspartate aminotransferase levels; wherein the antiviral comprises one or more of remdesivir, chloroquine, tenofovir, or a protease inhibitor.
Gorse et al. teach that HCoV infection has been viewed as a contributor to exacerbations of underlying chronic obstructive pulmonary disease (COPD), asthma, congestive heart failure, and severe illnesses requiring emergency care and hospitalization of patients with chronic medical conditions (See page 847). Gorse et al. teach that HCoV infections were clinically significant in patients ≥ 50 years of age with COPD and other illnesses (See page 852). Gorse et al. teach that the chronic other illnesses include diabetes mellitus and heart disease (See page 852 and table 3). Gorse et al. teach that more than 8-% of the HCoV-associated infections were characterized by new or increased cough, sputum production, nasal congestion, and fatigue and/or malaise (See page 853 and table 4).
Adler teaches that 2019-nCoV is a novel coronavirus on the rise and teaches that older adults may be particularly susceptible to respiratory illness, which can cause pneumonia and symptoms like fever, cough, and shortness of breath (See page 1). It should be noted that SARS-CoV-2 is the virus that causes 2019-nCoV. Alder teaches that people who are at higher risk for severe disease and death are those who are older and with underlying health conditions (See page 1). Alder teaches that the disease is more lethal in people over the age of 50 (See page 1).
Blatt, Gorse, and Adler do not teach wherein the subject has a viral load of at least 102, 103, 104, 105, 106, 107, or 108 coronavirus RNA copies per mL of sample.
However, Pan et al. discloses the viral load of SARS-CoV-2 from different types of clinical specimens from infected individuals (See page 411). Pan et al. teach that samples were analyzed by an N-specific quantitative RT-PCR assay (See page 411). Pan et al. teach that the viral loads in throat swab and sputum of infected individuals peaked at around 5-6 days after symptom onset, ranging from around 104 to 107 copies per ml (See page 411). Pan et al. teach that the viral load of respiratory samples and throat swabs ranges from 641 copies per mL to 1·34×10¹¹ copies per mL, with a median of 7·99 × 10⁴ in throat samples and 7·52 × 10⁵ in sputum samples (See page 411).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to treat a subject having a viral load of at least 102, 103, 104, 105, 106, 107, or 108 coronavirus RNA copies per mL of sample because Pan et al. teach that the viral load is an indicator of SARS-CoV2 infection. Further, knowing the initial viral load allows the clinician to establish a baseline from which the therapeutic efficacy of the interferon lambda can be measured. One of ordinary skill in the art would be motivated to treat a subject having a viral load of at least 102, 103, 104, 105, 106, 107, or 108 coronavirus RNA copies per mL of sample in order to ensure the severity of the coronavirus infection is reduced, e.g., the viral load is reduced and/or the time to viral clearance is reduced, and/or the morbidity or mortality is reduced.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses combining prior art elements according to known methods to yield predictable results, thus the combination is obvious unless its application is beyond that person's skill. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) also discloses that "The combination of familiar element according to known methods is likely to be obvious when it does no more than yield predictable results". The combination would have yielded a reasonable expectation of success along with predictable results to one of ordinary skill in the art at the time of the invention. Thus, it would have been obvious to a person of ordinary skill in the art to combine prior art elements according to known methods that is ready for improvement to yield predictable results. The claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 54-59, 61, 63-76 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 122-141 of copending Application No. 17/819,254 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are drawn to a method of treating coronavirus infection comprising administering interferon-lambda. Both sets of claims recite that the interferon is pegylated interferon. Both sets of claims recite the same patient population having the same preexisting conditions and the same dose of the interferon lambda. Both sets of claims recite administering a second antiviral agent and specify the same antiviral agents. Thus, the claims are of the same scope and not patentably distinct.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim Status
No claims are allowed.
Conclusion
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/SANDRA CARTER/Examiner, Art Unit 1674
/VANESSA L. FORD/Supervisory Patent Examiner, Art Unit 1674