DETAILED ACTION
Examiner acknowledges receipt of the reply filed 2/26/2026, in response to the restriction requirement mailed 11/26/2025.
Claims 1-20 are pending. Claims 7 and 11-14 are withdrawn from further prosecution for the reasons set forth herein.
Claims 1-6, 8-10, and 15-20 are being examined on the merits in this office 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 .
Priority
The filing receipt dated 10/05/2023 provides the following priority information:
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Election/Restrictions
Applicant’s election of the following species without traverse in the reply filed on 2/26/2026 is acknowledged:
Compound combination: interferon-α and rintatolimod
Viral infection: RNA virus, coronavirus
Claims 1-6, 10, and 15-20 read on the elected species.
Claims 7 and 11-14 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 2/26/2026.
Upon searching the elected species, an additional species was found e.g. poly(I:C). Accordingly, for purposes of compact prosecution, the election of species is modified only to the extent of examining this additional species. Otherwise the election of species requirement is still retained.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Specification
Please note, the specification has not been checked to the extent necessary to determine the presence of all possible error. Applicant's cooperation is required in correcting any errors of which applicant may become aware in the specification. MPEP § 608.01.
The use of the term AMPLIGEN, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Rejections - 35 USC § 112
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 1-6 and 15-20 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The metes and bounds of claim 1 are deemed to be indefinite. Claim 1 is drawn to a method for prophylaxis or therapy of a viral infection, the method comprising administering to an individual in need thereof a combination of at least two of: an interferon (IFN), a Toll-Like Receptor (TLR) ligand, poly(I:C), rintatolimod, tumor necrosis factor alpha (TNF-α) or an inducer thereof, nuclear factor kappa B (NF-Kβ) or an inducer or activator thereof. It is unclear from the claims as to what compound “inducer” and “activator”, respectively, refers back to. Under one claim interpretation, the claim scope encompasses an inducer or activator of any of the recited components, e.g. an inducer or an activator of an interferon (IFN). Alternatively, claim terms are limited to “TNF-α or an inducer thereof”, and “NF-Kβ, an inducer thereof, or an activator thereof”.
Claim clarification is required. Examiner recommends claim 1 be amended to recite semicolons and/or Roman numerals. The claim should also be amended to remove multiple recitations of the term “or”. The term “and” should be inserted between the last 2 compounds of the recited grouping.
Because claims 2-6 and 15-20 depend from indefinite claim 1 and do not clarify the point of confusion, they must also be rejected under 35 USC 112(b).
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 1-6, 8-10, and 15-20 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.
To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof.
The courts have stated:
“To fulfill the written description requirement, a patent specification must describe an invention and do 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 USPQ2d 1961, 1966 (1997); In re Gosteli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 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 at 1966.” Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
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. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient.” MPEP 2163.
Further, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents of the University of California v. Eli Lilly & Co., the court stated:
“A written description of an invention involving a chemical genus, like a description of a chemical species, 'requires a precise definition, such as by structure, formula, [or] chemical name,' of the claimed subject matter sufficient to distinguish it from other materials. Fiers, 984 F.2d at 1171, 25 USPQ2d at 1606; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284-85 (CCPA 1973) ("In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus. . . ."). Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The MPEP further states that if a biomolecule is described only by a functional characteristic, without any disclosed correlation between function and structure of the sequence, it is “not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence.” MPEP 2163. The MPEP does state that for generic claim the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. MPEP 2163. If the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. See MPEP 2163. Although the MPEP does not define what constitute a sufficient number of representative, the Courts have indicated what do not constitute a representative number species to adequately describe a broad generic. In Gostelli, the Court determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gostelli, 872 F.2d at 1012, 10 USPQ2d at 1618.
In making a determination of whether the application complies with the written description requirement of 35 U.S.C. 112, first paragraph, it is necessary to understand what Applicant is in possession of and what Applicant is claiming. The Federal Circuit has emphasized that "the hallmark of written description is disclosure" and "[t]hus, ‘possession as shown in the disclosure’ is a more complete formulation." Ariad, 598 F.3d at 1351, 94 USPQ2d at 1172. Accordingly, "the test requires an objective inquiry into the four corners of the specification from the perspective of a person of ordinary skill in the art" and "[b]ased on that inquiry, the specification must describe an invention understandable to that skilled artisan and show that the inventor actually invented the invention claimed." Id.
The instant claims are drawn to a method for prophylaxis or therapy of a viral infection, the method comprising administering to an individual in need thereof a combination of at least two of: an interferon (IFN), a Toll-Like Receptor (TLR) ligand, poly(I:C), rintatolimod, tumor necrosis factor alpha (TNF-α) or an inducer thereof, nuclear factor kappa B (NF-Kβ) or an inducer or activator thereof.
The specification does not define the terms “activator” or “inducer”. An “activator” or “inducer” could directly or indirectly affect gene expression, protein expression, or receptor activity. Compounds could further act upstream. The scope of compounds that fall within the claim scope is unclear. Please also see the related, but separate, indefinite/112(b) rejection set forth herein.
Treating or prophylaxis of a viral infection was not reduced to practice. Example 1 purports that different combinations of an interferon and a second therapeutic (poly-IC, rintatolimod, or TNFα) altered gene expression similar for antiviral activity. The Example did not assess any virus. Example 1 asserts synergy but does not clearly disclose any such results given the lack of the presence of any virus. It is noted that Fig 1 does not disclose any error bars. The statistical relevance is unclear. Example 1 appears to makes conclusory statements but fails to provide sufficient experimental details and data.
Table 1 discloses specific combinations of the claimed compounds, e.g., IFNα/rintatolimod, IFNα/poly-IC, IFNα/TNFα, IFNγ/rintatolimod, IFNγ/poly-IC, IFNγ /TNFα. No TLR3 ligands other than poly-IC and rintatolimod were reduced to practice. No inducers or activators of TNFα were reduced to practice. No inducers or activators of NF-Kβ were reduced to practice. NF-Kβ was not reduced to practice.
The specification cites various journal articles. However, 37 CFR §1.57 (d) states "Essential material" may be incorporated by reference, but only by way of an incorporation by reference to a U.S. patent or U.S. patent application publication, which patent or patent application publication does not itself incorporate such essential material by reference. See also MPEP §608.01(p).
The specification does not discloses therapeutically effective amounts of the claimed compounds, much less routes of administration, and dosing regimens.
There are no examples of treatment, much less any “inducers” or “activators” set forth in the specification. The skilled artisan cannot envision the combinations of claimed interferons, TNFa, TLR ligands, poly I:C, rintatolimod, and NF-Kβ, and amounts thereof, that can be used to treat and prevent (prophylaxis) a viral infection. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description.
The description requirement of the patent statute 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) (affirming rejection because the specification does "little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate"). Accordingly, it is deemed that the specification fails to provide adequate written description for the genus of the claims and does not reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the entire scope of the claimed invention.
Claims 1-6, 8-10, and 15-20 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating a viral infection comprising a combination of interferon and rintatolimod/poly-I:C, does not provide enablement for prophylaxis of a viral infection. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
“[T]o be enabling, the specification of a patent must teach those skilled in the art how to make and use the full scope of the claimed invention without ‘undue experimentation.’” Genentech Inc. v. Novo Nordisk 108 F.3d 1361, 1365, 42 USPQ2d 1001, 1004 (Fed. Cir. 1997); In re Wright 999 F.2d 1557, 1561, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993); See also Amgen Inc. v. Chugai Pharm. Co., 927 F.2d 1200, 1212, 18 USPQ2d 1016, 1026 (Fed. Cir. 1991); In re Fisher 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). Further, in In re Wands 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988) the court stated:
Factors to be considered in determining whether a disclosure would require undue experimentation have been summarized by the board in Ex parte Forman [230 USPQ 546, 547 (BdPatAppInt 1986)]. They include (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredict-ability of the art, and (8) the breadth of the claims.
A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557,1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).
Nature of the Invention and Breadth of the Claims
Claim 1 is drawn to a method for prophylaxis or therapy of a viral infection, the method comprising administering to an individual in need thereof a combination of at least two of: an interferon (IFN), a Toll-Like Receptor (TLR) ligand, poly(I:C), rintatolimod, tumor necrosis factor alpha (TNF-α) or an inducer thereof, nuclear factor kappa B (NF-Kβ) or an inducer or activator thereof.
Claim 15 recites wherein the individual is in need of prophylaxis or therapy for an RNA viral infection. Claims 17-20 recite specific forms of RNA viruses e.g., SARS-CoV-2.
State of the Prior Art
Examiner notes that the following references are a brief selection that fall within the instant claim scope, but is not comprehensive of the full claim scope.
A search of the art did not uncover a single agent that can treat/prevent all viral infections, as well as all subjects that fall within the claim scope.
The Merck Manual (.merckmanuals.com/professional/infectious- diseases/viruses/overview-of-viruses accessed 2/19/19) teaches viruses are DNA and RNA based and require host cell machinery to reproduce. For infection to occur, the virus first attaches to the host cell at one or one of several receptor molecules on the cell surface. The viral DNA or RNA then enters the host cell and separates from the outer cover (uncoating) and replicates inside the host cell in a process that requires specific enzymes. The newly synthesized viral components then assemble into a complete virus particle. The host cell typically dies, releasing new viruses that infect other host cells. The consequences of viral infection vary considerably. Many infections cause acute illness after a brief incubation period, but some are asymptomatic or cause minor symptoms that may not be recognized except in retrospect. Many viral infections are cleared by the body’s defenses, but some remain in a latent state, and some cause chronic disease. Some disorders are caused by viral reactivation in the CNS after a very long latency period. These diseases include progressive multifocal leukoencephalopathy (due to the JC virus, a polyomavirus), subacute sclerosing panencephalitis (due to measles virus), and progressive rubella panencephalitis (due to rubella virus). Several hundred different viruses infect humans but vary by way of transmission method (respiratory, enteric, sexually transmitted, etc.). Other viruses are further associated with certain forms of cancer. Treatment can involve antivirals that affect viral replication (e.g., viral particle attachment to host cell, cellular replication, or enzymes). Interferon therapy is another form of viral treatment. Although several antiviral agents have been shown to treat more than one form of virus (e.g., HIV and hepatitis B), there is no one shoe fits all scenario. In part, this is due to the type of cell and location of the virus which are highly variable across all forms of viruses (affecting plants, bacterium, and animals).
Hu et al. (Nature Rev Microbiol. 19:141-154 (2021)) is review article discussing characteristics of SARS-CoV-2 and COVID-19. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible and pathogenic coronavirus that emerged in late 2019 and has caused a pandemic of acute respiratory disease, named ‘coronavirus disease 2019’ (COVID-19) (abstract). As a novel betacoronavirus, SARS-CoV-2 shares 79% genome sequence identity with SARS-CoV and 50% with MERS-CoV24. Its genome organization is shared with other betacoronaviruses. The six functional open reading frames (ORFs) are arranged in order from 5′ to 3′: replicase (ORF1a/ORF1b), spike (S), envelope (E), membrane (M) and nucleocapsid (N) (p. 142). SARS-CoV-2 uses the same receptor as SARS-CoV, angiotensin-converting enzyme 2 (ACE2)11,47. Besides human ACE2 (hACE2), SARS-CoV-2 also recognizes ACE2 from pig, ferret, rhesus monkey, civet, cat, pangolin, rabbit and dog11,43,48,49. The broad receptor usage of SARS-CoV-2 implies that it may have a wide host range, and the varied efficiency of ACE2 usage in different animals may indicate their different susceptibilities to SARS-CoV-2 infection *p. 146). To date, there are no generally proven effective therapies for COVID-19 or antivirals against SARS-CoV-2, although some treatments have shown some benefits in certain subpopulations of patients or for certain end points (see later). Researchers and manufacturers are conducting large-scale clinical trials to evaluate various therapies for COVID-19 (p. 149). Fig. 5 indicates SARS-CoV-2 replication and potential therapeutic targets.
Carter (U.S. 2006/0035859) discloses treatment of a severe acute respiratory syndrome (SARS) virus comprising administering a natural human alpha interferon and a dsRNA to an infected subject (e.g., abstract, paras. [0002]-[0003], [0006]-[0012], [0016]-[0021], example 1, claims 1-6). dsRNA includes poly(I:C) and Ampligen (also known as rintatolimod, e.g., specification at para [0006]) (e.g., paras [0013]-[0022] example 1, claim 3).
Relative Skill of those in the Art
MPEP 2141.03 states (in part)” A person of ordinary skill in the art is also a person of ordinary creativity, not an automaton.” KSR International Co. v. Teleflex Inc., 127 S.Ct. 1727, 167 LEd2d 705, 82 USPQ2d 1385, 1397 (2007). “[I]n many cases a person of ordinary skill will be able to fit the teachings of multiple patents together like pieces of a puzzle.” Id. Office personnel may also take into account “the inferences and creative steps that a person of ordinary skill in the art would employ.” Id. At 1396, 82 USPQ2d at 1396. The “hypothetical person having ordinary skill in the art’ to which the claimed subject matter pertains would, of necessity have the capability of understanding the scientific and engineering principles applicable to the pertinent art.” Ex parte Hiyamizu, 10 USPQ2d 1393, 1394 (Bd. Pat. App. & Inter. 1988) (disagreeing with the examiner’s definition of one of ordinary skill in the art (i.e. a doctorate level engineer or scientist working at least 40 hours per week in semiconductor research or development), and finding that the hypothetical person is not definable by way of credentials, and that the evidence in the application did not support the conclusion that such a person would require a doctorate or equivalent knowledge in science or engineering). In the instant case, the skill in the art high with respect to physicians and scientists. The level of skill in the art (physicians and scientists) would be high.
Predictability or Unpredictability of the Art
It is noted that pharmaceutical and biological art is generally unpredictable, requiring each embodiment to be individually assessed for physiological activity. Given this fact, historically the development of new drugs has been difficult and time-consuming. Adding to the unpredictability is that many treatment options may show promise in animal models, but may fail to show therapeutic improvement in clinical trials. There is no absolute predictability, even in view of the high level of skill in the art.
The invention is directed toward medicine and is therefore physiological in nature. It is well established that “the scope of enablement varies inversely with the degree of unpredictability of the factors involved,” and physiological activity is generally considered to be an unpredictable factor. See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).
Examiner notes that for prophylaxis of a viral infection, the skilled artisan must be apprised of patients that are at risk of developing a viral infection, as well as combinations of the cited compounds, dosage amounts, treatment regimens and routes of administration necessary to prophylactically treat/prevent a viral infection
There are no examples of prophylaxis of any viral infection.
Amount of Direction or Guidance Given and Presence/Absence of Working Examples
The specification does not provide sufficient guidance or direction regarding the prophylaxis of a viral infection. The specification does not provide any examples indicating prophylaxis of any viral infection.
The specification does not discloses therapeutically effective amounts of the claimed compounds, much less routes of administration, and dosing regimens.
Table 1 discloses specific combinations of the claimed compounds, e.g., IFNα/rintatolimod, IFNα/poly-IC, IFNα/TNFα, IFNγ/rintatolimod, IFNγ/poly-IC, IFNγ /TNFα. No TLR3 ligands other than poly-IC and rintatolimod were reduced to practice. No inducers or activators of TNFα were reduced to practice. No inducers or activators of NF-Kβ were reduced to practice. NF-Kβ was not reduced to practice.
The specification does not disclose any examples in which the claimed combination of compounds were actually shown to treat a viral infection.
Figure 1 legend states:
Figure 1 provides a summary of data showing synergy between double- stranded (ds)RNA species, such as rintatolimod or poly-I:C, type-1 and type-2 Interferons (IFNα and IFNγ), and inflammatory cytokine (known NFκβ activator) TNFα in the induction of cell-intrinsic mediators of SARS-Co-V2 immunity. Human epithelial cells (SW620) were cultured overnight in the absence or presence of the indicated combinations of rintatolimod (100 ug/ml), IFNα (1000U/ml), IFNγ (1000U/ml) and TNFα (25ng/ml), before mRNA extraction and Taqman analysis.
Specification at para. [0004]. The figure legend does not indicate that the cells were incubated with any virus, only that SW620 [human epithelial] cells were cultured in the absence or presence of various compounds e.g., polyI:C (PIC), IFNγ, rintatolimod (Amp) and TNFα.
Example 1 states at para [0023]:
We analyzed cell and tissue samples used to evaluate antiviral synergy using rintatolimod (or poly-I.C) with IFNα, developed as immunostimulatory cocktail with anti-cancer activity in inducing the chemokines mediating intratumoral attraction of CTLs, Th1 and NK cells, for the induction of genes involved in SARS-Cov elimination, observing synergistic effects on several of these target genes (see Figure 1). The synergy in inducing OAS2 (OASs are key activators of RNAse-L, which is not transcriptionally regulated, but activated by OASs which detect dsRNA in order to degrade genetic material of RNA viruses'), as well as Ifit-1, Mx1, RIG-I, MDA5, TLR3 and several other ISGs/IFN-regulated genes implicated in the intrinsic resistance of epithelial cells to RNA viruses', provides support for the application of this combination therapy in patients at early stages of COVID19. A similar synergy in the induction of these cell-intrinsic anti-viral factors was also seen using the combination of TNFα and IFN. The antiviral effects of the AMPLIGEN/ IFNα combination against SARS-Cov-2 have been confirmed in BSL3 conditions.
The Example does not include any virus. Instead, the example purports the markers tested are implicated in SARS-CoV/COVID infection. The example purports synergy but does not clearly disclose any such results given the lack of the presence of any virus. No treatment of a viral infection was actually reduced to practice. It is noted that Fig 1 does not disclose any error bars. The statistical relevance is unclear. Example 1 appears to makes conclusory statements but fails to provide sufficient experimental details and data.
It is noted that 37 CFR §1.57 (d) states "Essential material" may be incorporated by reference, but only by way of an incorporation by reference to a U.S. patent or U.S. patent application publication, which patent or patent application publication does not itself incorporate such essential material by reference. See also MPEP §608.01(p).
There is no evidence that the claimed combination of therapeutics would provide prophylaxis/prevent a viral infection. In order to prevent, the skilled artisan must be able to identify patients at risk of developing a given viral infection, as well as administer a sufficient dose/route of administration/dosing regimen of the claimed drug combination. The specification does not provide any such guidance to the skilled artisan.
Though not controlling, the lack of working examples [prophylaxis/prevent a viral infection], is, nevertheless, a factor to be considered in a case involving both physiological activity and an undeveloped art. When a patent applicant chooses to forego exemplification and bases utility on broad terminology and general allegations, he runs the risk that unless one with ordinary skill in the art would accept the allegations as obviously valid and correct, the PTO may, properly, ask for evidence to substantiate them. Ex parte Sudilovsky, 21 USPQ2d 1702, 1705 (BPAI 1991); In re Novak, 134 USPA 335 (CCPA 1962); In re Fouche, 169 USPQ 429 (CCPA 1971).
In essence, the specification merely presents an idea of, and leaves it entirely up to the practitioner to determine whether the method would produce a therapeutically relevant effect, and if so, how to carry out the claimed method. It has been established by legal decision that a patent is not a hunting license. It is not a reward for the search, but compensation for its successful conclusion. Tossing out the germ of an idea does not constitute an enabling disclosure. While every aspect of a generic claim need not have been carried out by an inventor, or exemplified in the specification, reasonable detail must be provided in order to enable the skilled artisan to understand and carry out the invention. It is true that a specification need not disclose what is well known in the art. However, that general, oft-repeated statement is merely a rule of supplementation, not a substitute for a basic enabling disclosure. It means that the omission of minor details does not cause a specification to fail to meet the enablement requirement under 35 USC 112, first paragraph. When there is no disclosure of the specific starting materials or conditions under which the process can be carried out, there is a failure to meet the enablement requirement. See Genentech Inc. v. Novo Nordisk A/S, 42 USPQ2d 1001, 1005 (Fed. Cir. 1997).
Quantity of Experimentation Necessary
Owing to the factors listed above, especially in points 1-7, the amount of experimentation needed will be extensive in view of the lack of guidance by the inventor. MPEP 2164.01(a) states, “A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557,1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).” That conclusion is clearly justified here.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1-6, 8, 9, and 15-18 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Tianjin Ringpu Bio Technology Co Ltd (CN101874896, published 2010; “CN896”; - cited in IDS filed 4/20/2023). Examiner refers to the CN101874896 machine translation, provided herewith.
CN896 discloses a combination of interferon-alpha and a immunopotentiator, e.g., polyinosinic-polycytidylic acid (poly-I:C) (e.g., paras [0011]-[0015], [0033]-[0050], claims 1-2). The combination is used to treat viral infections in pigs (e.g., paras. [0004], [0092]- [0108]). Accordingly, the limitations of claims 1, 4, 5, 8, and 9 are satisfied.
Regarding claims 2 and 3, CN896 teaches polyinosinic-polycytidylic acid (poly-I:C). Regarding claim 6, CN896 teaches that interferon alpha includes interferon-alpha 1 and interferon-alpha 2 (para. [0006]). Regarding claims 15-18, CN896 disclose that the virus can be Porcine Epidemic Diarrhea Virus (PEDV) or transmissible gastroenteritis virus (TGEV), belonging to coronaviruses [reads on Coronaviridae].
Regarding claim 16, CN896 discloses that the combination has a synergistic effect over alpha-interferon (para [0002]).
Claim(s) 1-6, 8-10, and 15-19 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Carter (U.S. 2006/0035859).
Carter discloses treatment of a severe acute respiratory syndrome (SARS) virus comprising administering a natural human alpha interferon and a dsRNA to an infected subject (e.g., abstract, paras. [0002]-[0003], [0006]-[0012], [0016]-[0021], example 1, claims 1-6). dsRNA includes poly(I:C) and Ampligen (also known as rintatolimod, e.g., specification at para [0006]) (e.g., paras [0013]-[0022] example 1, claim 3). Accordingly, the limitations of claims 1-5 and 8-10 are satisfied.
Regarding claim 6, Carters teaches that interferon alpha/ α-interferon component can be a single molecular species of α-interferon or a mixture of species of α-interferon. Alferon N Injection® is a mixture of at least seven species of alpha interferon (α2, α4, α7, α8, α10, α16, α17) (e.g., paras [0009]-[0010], [0019]). The high purity of Alferon N Injection® and its advantage as a natural mixture of seven interferon species, some of which, like species 8b, have greater antiviral activities than other species (para. [0010]).
Regarding claims 15 and 17-19, Carter discloses that the virus can be a severe acute respiratory syndrome virus (SARS-CoV) [reads on Coronaviridae] (e.g., paras. [0002]-[0003], [0006]-[0012], [0016]-[0021], example 1, claims 1-6). Carter further taught treatment of an avian influenza virus (e.g., paras. [0026]-[0029], claims 9-13).
Regarding claim 16, Carter discloses that the combination has a synergistic effect (e.g., paras [0021]-[0028], Ex 4).
Pursuant to MPEP 2121(I), when the reference relied on expressly anticipates or makes obvious all the elements of the claimed invention, the reference is presumed to be operable. Once such a reference is found, the burden is on applicant to rebut the presumption of operability. In re Sasse, 629 F.2d 675, 207 USPQ 107 (CCPA 1980). Moreover, MPEP 2121(III) states that a prior art reference provides an enabling disclosure and thus anticipates a claimed invention if the reference describes the claimed invention in sufficient detail to enable a person of ordinary skill in the art to carry out the claimed invention; "proof of efficacy is not required for a prior art reference to be enabling for purposes of anticipation." Impax Labs. Inc. v. Aventis Pharm. Inc., 468 F.3d 1366, 1383, 81 USPQ2d 1001, 1013 (Fed. Cir. 2006). MPEP 716.07 states that since in a patent it is presumed that a process if used by one skilled in the art will produce the product or result described therein, such presumption is not overcome by a mere showing that it is possible to operate within the disclosure without obtaining the alleged product. In re Weber, 405 F.2d 1403, 160 USPQ 549 (CCPA 1969).
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.
Claim(s) 1-6, 8-10, and 15-20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Carter (U.S. 2006/0035859), as evidenced by Hu et al. (Nature Rev Microbiol. 19:141-154 (2021)).
Carter discloses treatment of a severe acute respiratory syndrome (SARS) virus comprising administering a natural human alpha interferon and a dsRNA to an infected subject (e.g., abstract, paras. [0002]-[0003], [0006]-[0012], [0016]-[0021], example 1, claims 1-6). dsRNA includes poly(I:C) and Ampligen (also known as rintatolimod, e.g., specification at para [0006]) (e.g., paras [0013]-[0022] example 1, claim 3).
Although Carter et al do not explicitly disclose the name “SARS-Cov-2”, Carter expressly teaches administering interferon-alpha and a dsRNA (poly-I:C or Ampligen (also known as rintatolimod)) to a subject with a coronavirus viral infection in order to treat the coronavirus viral infection. As evidenced by Hu et al., SARS-CoV-2 is a coronavirus (p. 141). The term “SARS-CoV-2” was first coined on February 11, 2020 by the World Health Organization (WHO) (Hu et al at p.142).
Thus, administering alpha interferon and a dsRNA (poly-I:C or Ampligen/ rintatolimod) to a subject with a SARS-CoV-2 (coronavirus) viral infection in order to treat the SARS-CoV-2 (coronavirus) viral infection is rendered obvious in view of the teachings of Carter. The skilled artisan would have had a reasonable expectation of success because Carter expressly taught the compounds (alpha-interferon and either poly-I:C or Ampligen/ rintatolimod [dsRNA]) could be used in treating an individual with a coronavirus and a SARS virus infection. Thus, an individual with a SARS-CoV-2 virus was the patient population that Carter sought to treat. Claim 20 is rendered obvious.
Claims 1-6, 8-10, and 15-20 are obvious in view of the teachings of Carter.
Pursuant to MPEP 2121(I), when the reference relied on expressly anticipates or makes obvious all the elements of the claimed invention, the reference is presumed to be operable. Once such a reference is found, the burden is on applicant to rebut the presumption of operability. In re Sasse, 629 F.2d 675, 207 USPQ 107 (CCPA 1980). Moreover, MPEP 2121(III) states that a prior art reference provides an enabling disclosure and thus anticipates a claimed invention if the reference describes the claimed invention in sufficient detail to enable a person of ordinary skill in the art to carry out the claimed invention; "proof of efficacy is not required for a prior art reference to be enabling for purposes of anticipation." Impax Labs. Inc. v. Aventis Pharm. Inc., 468 F.3d 1366, 1383, 81 USPQ2d 1001, 1013 (Fed. Cir. 2006). MPEP 716.07 states that since in a patent it is presumed that a process if used by one skilled in the art will produce the product or result described therein, such presumption is not overcome by a mere showing that it is possible to operate within the disclosure without obtaining the alleged product. In re Weber, 405 F.2d 1403, 160 USPQ 549 (CCPA 1969).
Conclusion
No claims are allowed.
Claims 1-20 are pending. Claims 7 and 11-14 are withdrawn.
Claims 1-6, 8-10, and 15-20 are rejected.
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/KRISTINA M HELLMAN/Examiner, Art Unit 1654
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