DETAILED ACTION
Examiner acknowledges receipt of the reply filed 8/11/2026, in response to the non-final office action mailed 5/14/2026.
Claims 1-15 and 17-20 are pending. Claim 16 has been cancelled. Claims 7 and 11-14 remain withdrawn from further prosecution for the reasons made of record.
Claims 1-6, 8-10, 15, and 17-20 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 .
Specification- withdrawn
The objection to the specification is withdrawn in view of the amendment filed 8/11/2026.
Claim Rejections - 35 USC § 112- withdrawn
The rejection of claims 1-6 and 15-20 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn in view of the amendment filed 8/11/2026.
The rejection of claims 1-6, 8-10, and 15-20 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph (scope of enablement), is withdrawn in view of the amendment filed 8/11/2026.
Response to Arguments
Applicant’s amendment filed 8/11/2026 with respect to the above objections and rejections have been fully considered and are persuasive. The objections and rejections have been withdrawn.
Applicant's arguments and amendment filed 8/11/2026 have been fully considered but they are not persuasive.
An action on the merits is set forth herein.
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.
Claim Rejections - 35 USC § 112- maintained
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, 15, and 17-20 remain/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 rejection is maintained from the office action mailed 5/14/2026, but has been amended to reflect claims filed 8/11/2026.
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 therapy of a viral infection, the method comprising administering to an individual in need thereof a combination of at least two of: (i) an interferon (IFN); (ii) a Toll-Like Receptor (TLR) ligand; (iii) poly(I:C); (iv) rintatolimod; (v) tumor necrosis factor alpha (TNF-α) or an inducer of TNF-α; and (vi) nuclear factor kappa B (NF-kB), an inducer of NF-kB, or an activator of NF-kB, wherein the combination exhibits a synergistic anti-viral effect.
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 act further upstream. The scope of compounds that fall within the claim scope is unclear.
The scope of what exactly constitutes “synergistic anti-viral effect” is unclear based on the specification.
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, but shows no data relating to a viral 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 make conclusory statements but fails to provide sufficient experimental details and data. Guidance relating to gene expression cannot be conflated to, nor does it substitute for data relating to treatment of a viral infection that actually the virus.
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.
It is further noted that instant claim 1 provides that a combination of at least 2 [any two] of the recited compounds yields a “synergistic ant-viral effect”. However, Example 1 is limited to requiring an interferon as one of the two recited compounds. This further indicates lack of guidance within the specification as to whether or not a combination of the recited elements, not including an interferon (e.g., a combination of TNFa and NF-Kβ) would give rise to a synergistic antiviral effect.
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 a viral infection, much less provide “synergy”. 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.
Response to Arguments
Applicant traversed the rejection at pp 6-7 of the reply filed 8/11/2026. Applicant states at p. 9: claim 1 was amended to clarify that "an inducer" and "an activator" refer specifically to an inducer of TNF-α and to an inducer or activator of NF-kB, respectively as supported by the specification. This removes the ambiguity that formed the basis of the written description rejection.
Applicant asserts that the claimed agents share a common, art-recognized mechanism of action, e.g. inducer activate type 1 interferon response of genes and other cell intrinsic effectors that confer intrinsic cellular resistance to RNA viruses, referring to para [0023] of the specification. Id. Applicant asserts that TLR ligands, including TLR3 ligands such as poly(I:C) and rintatolimod, are recognized in the art as inducers of interferon singling, and that TNF-alpha and NF-KB activate overlapping and related signaling pathways that converge on the same antiviral gene program demonstrated in Example 1 and Figure 1. Applicant asserts that the members of the claimed genus are unified by this common, disclosed mechanism and the specific combinations reduced to practice in example 1 are representative of the genus and reasonably convey that the inventor had possession at the time of filing. Id.
Examiner has reviewed and considered applicants arguments, but is not persuaded.
The skilled artisan cannot extrapolate to all iterations of compounds that fall within the umbrella terms “inducer of TNF-α”, “inducer of NF-κβ”, or “activator of NF-κβ” where such compounds were not reduced to practice. As noted in the rejection, inducers or activators could directly or indirectly affect gene expression, protein expression, or receptor activity. The specification lacks guidance as to effective amounts necessary to achieve therapy of a viral infection across any and all species of viruses. Applicant did not address this part of the rejection.
Moreover, the specification lacks guidance as to which combinations of compounds can give rise to a combination of recited compounds that exhibit “a synergistic anti-viral effect”. Examiner reiterates that no examples of treating a viral infection were reduced to practice, as required by the instant claims. The specification is further limited to a disclosure of SARS-CoV-2. The example disclosed in the specification purports synergy as indicated by a change in gene expression of genes involved in SARS-CoV elimination. However, no actual viruses were treated, as required by the instant claims. A change in gene expression cannot be conflated with actual treatment of a virus.
Vas-Cath Inc. V. Mahukar, 19USPQ2d 1111, clearly states, "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).
Adequate written description requires more than a mere statement that is part of the invention and reference to a potential method of using it. The compound itself is required. See Fiers V. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. V. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. One cannot describe what one has not conceived. See Fiddes V. Baird, 30 USPQ2d 1481 at 1483.
The rejection is maintained for at least these reasons, and those previously made of record.
Claim Rejections - 35 USC § 102- maintained
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, 15, 17, and 18 remain/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Tianjin Ringpu Bio Technology Co Ltd (CN101874896, published 2010; “CN896”; - previously cited). Examiner refers to the CN101874896 machine translation, provided herewith. The rejection is maintained from the office action mailed 5/14/2026, but has been amended to reflect claims filed 8/11/2026.
CN896 discloses a combination of interferon-alpha and an 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]). CN896 discloses that the combination has a synergistic effect over alpha-interferon (para [0002]). Accordingly, the limitations of claims 1, 4, 5, 8, and 9 are satisfied.
MPEP § § 2112- 2112.02 states that when a reference discloses all the limitations of a claim except a property or function, and the examiner cannot determine whether or not the reference inherently possesses properties which anticipate or render obvious the claimed invention but has basis for shifting the burden of proof to applicant as in In re Fitzgerald, 619 F.2d 67, 205 USPQ 594 (CCPA 1980).
Here, CN896 expressly teaches a combination of interferon-alpha and polyinosinic-polycytidylic acid (poly-I:C) for treating viral infections in pigs (e.g., Porcine Epidemic Diarrhea Virus (PEDV) or transmissible gastroenteritis virus (TGEV), belonging to coronaviruses [reads on Coronaviridae]). CN896 expressly states “The invention belongs to the technical field of medicines, and relates to a recombinant porcine alpha-interferon and a combined medicine with a synergistic effect on the recombinant porcine alpha-interferon” (para [0002]).
The Patent and Trademark Office is not equipped to conduct experimentation in order to determine whether or not applicants' claimed combination of an interferon and poly(I:C) and treating a viral infection, and if so to what extent, differs from CN896 with regard to synergy. Examiner reiterates that CN896 teaches the claimed combination (interferon-alpha and (poly-I:C)) has a synergistic effect and further teaches the combination for treatment of a viral infection. The cited art taken as a whole demonstrates a reasonable probability that the synergy of CN896 is either identical or sufficiently similar to the claimed effect that whatever differences exist are not patentably significant. Therefore, the burden of establishing novelty by objective evidence is shifted to applicants.
It is further noted that 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) and In re Tomlinson, 363 F.2d 928, 150 USPQ 623 (CCPA 1966). See M.P.E.P. § 2112.02.
CN896 teach administration of a combination of interferon-alpha and (poly-I:C) to treat a viral infection. The reference performs the same method steps as instantly claimed. Because the method steps (administering combination of interferon-alpha and (poly-I:C) to a subject with a viral infection) are the same, CN896 inherently teach the same process of synergistic anti-viral effects as in the current application. CN896 therefore anticipates the synergistic anti-viral effects of a combination of interferon-alpha and (poly-I:C) in treating a viral infection as instantly claimed.
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].
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).
Response to Arguments
Applicant traverses the rejection at pp. 8-9. Applicant asserts that “CN896 does not report or suggest that the disclosed combinations produce a synergistic anti-viral effect, namely that the antiviral effect is greater than the sum of the effects of the individual agents administered alone, nor does it disclose any data, such as the gene induction data presented in Figure 1 of the present application, from which such synergy could be discerned” (reply at p. 9). Applicant asserts that the CN896 does not anticipate the instant claims.
Examiner has reviewed and considered Applicant’s arguments, but is not persuaded.
As noted in the instant rejection, CN896 explicitly teaches a combination of interferon-alpha and (poly-I:C) in treating a viral infection. The reference further explicitly states that the combination is synergistic. MPEP § § 2112- 2112.02 states that when a reference discloses all the limitations of a claim except a property or function, and the examiner cannot determine whether or not the reference inherently possesses properties which anticipate or render obvious the claimed invention but has basis for shifting the burden of proof to applicant as in In re Fitzgerald, 619 F.2d 67, 205 USPQ 594 (CCPA 1980).
Additionally, CN896 is deemed to inherently teach a synergistic anti-viral effect. CN896 teaches the claimed drug combination (interferon-alpha and (poly-I:C)) administered to the same claimed patient population (viral infection). See M.P.E.P. § 2112.02.
Regarding applicant’s assertions that CN896 does not disclose the data such as presented in Fig 1, MPEP 2121(I) indicates that when the reference relied on expressly anticipates or makes obvious all the elements of the claimed invention, the reference is presumed to be operable. 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).
The rejection is maintained for at least these reasons and those previously made of record.
Claim(s) 1-6, 8-10, 15, and 17-19 remain/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Carter (U.S. 2006/0035859- previously cited). The rejection is maintained from the office action mailed 5/14/2026, but has been amended to reflect claims filed 8/11/2026.
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). Carter discloses that the combination has a synergistic effect (e.g., paras [0021]-[0028]).
Carter expressly states at para [0021]: It is also reported the activity of interferon can potentially be amplified by the addition of a double-stranded RNA drug, Ampligen®. While interferon up-regulates certain intracellular antiviral pathways, dsRNAs, like Ampligen®, are required to fully activate these important antiviral pathways. When interferons are combine[d] with Ampligen® synergistic antiviral and antitumor effects are seen. Moreover, Ampligen® has already shown strong antiviral activity in two separate animal models of the coronavirus (MHV-3). Carter expressly taught that a combination of an interferon and Ampligen exhibited a synergistic anti-viral effect against HIV, an RNA virus (para [0022]).
MPEP § § 2112- 2112.02 states that when a reference discloses all the limitations of a claim except a property or function, and the examiner cannot determine whether or not the reference inherently possesses properties which anticipate or render obvious the claimed invention but has basis for shifting the burden of proof to applicant as in In re Fitzgerald, 619 F.2d 67, 205 USPQ 594 (CCPA 1980).
Here, Carter expressly teaches a combination of Ampligen and interferon for treating HIV and a coronavirus.
The Patent and Trademark Office is not equipped to conduct experimentation in order to determine whether or not applicants' claimed combination of an interferon and poly(I:C) and treating a viral infection, and if so to what extent, differs from Carter with regard to synergy. Examiner reiterates that Carter teaches the claimed combination (interferon and Ampligen) has a synergistic effect and further teaches the combination for treatment of a viral infection. The cited art taken as a whole demonstrates a reasonable probability that the synergy of the drug combination taught by Carter is either identical or sufficiently similar to the claimed effect that whatever differences exist are not patentably significant. Therefore, the burden of establishing novelty by objective evidence is shifted to applicants.
It is further noted that 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) and In re Tomlinson, 363 F.2d 928, 150 USPQ 623 (CCPA 1966). See M.P.E.P. § 2112.02.
Carter teach administration of a combination of interferon and dsRNA (Ampligen or poly(I:C)) to treat a viral infection. The reference performs the same method steps as instantly claimed. Because the method steps (administering combination of interferon and Ampligen/ poly(I:C)) are the same, Carter inherently teach the same process of synergistic anti-viral effects as in the current application. Carter therefore anticipates the synergistic anti-viral effects of a combination of interferon and Ampligen/ poly(I:C) in treating a viral infection as instantly claimed.
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).
Response to Arguments
Applicant traverses the rejection at pp. 8-9. Applicant asserts that “Carter's coronavirus-specific disclosure is presented separately from, and is not tied to, its HIV/tumor synergy data: Carter does not disclose any experiment, result, or data showing that interferon and a dsRNA produce a synergistic (as opposed to additive) effect against SARS-CoV, MHV-3, or any other coronavirus. Carter's general statement of synergy in one viral/cellular system does not, without more, disclose synergy in a materially different system” (reply at p. 9). Applicant refers to the separate enablement rejection for the assertion that “well- documented unpredictability of antiviral pharmacology recognized by the Office action's own citation to In re Fisher, 427 F.2d 833, 839 (CCPA 1970) in the § 112(a) rejection”. Id. Applicant states at p. 9: Because Carter's coronavirus embodiments are not shown to be synergistic, Carter does not disclose the synergy limitation of claim 1 as applied to the RNA viruses recited in dependent claims 15 and 17-19.
Examiner has reviewed and considered Applicant’s arguments, but is not persuaded.
Examiner first notes that patents and applications are relevant as prior art for all they contain. "The use of patents as references is not limited to what the patentees describe as their own inventions or to the problems with which they are concerned. They are part of the literature of the art, relevant for all they contain." In re Heck, 699 F.2d 1331, 1332-33, 216 USPQ 1038, 1039 (Fed. Cir. 1983). A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill the art, including nonpreferred embodiments. Merck & Co. v. Biocraft Laboratories, 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989).
Carter expressly taught that a combination of an interferon and Ampligen exhibited a synergistic anti-viral effect against HIV, an RNA virus (para [0022]).
Thus, claim 1 is anticipated at least by this teaching.
As noted in the instant rejection, Carter explicitly teaches a combination of interferon and Ampligen/(poly-I:C) in treating a viral infection. The reference further explicitly states that the combination is synergistic. MPEP § § 2112- 2112.02 states that when a reference discloses all the limitations of a claim except a property or function, and the examiner cannot determine whether or not the reference inherently possesses properties which anticipate or render obvious the claimed invention but has basis for shifting the burden of proof to applicant as in In re Fitzgerald, 619 F.2d 67, 205 USPQ 594 (CCPA 1980).
Additionally, Carter is deemed to inherently teach a synergistic anti-viral effect. Carter teaches the claimed drug combination (interferon and Ampligen/(poly-I:C)) administered to the same claimed patient population (viral infection). See M.P.E.P. § 2112.02.
Examiner expressly notes that Applicant’s comment regarding the enablement rejection is taken out of context. The enablement rejection (withdrawn herein) related to previous claims that included prevention claim language. Thus, the enablement rejection related to unpredictably of preventing a viral infection.
In contrast, Carter teaches the claimed combination of an interferon and a dsRNA (e.g., Ampligen or poly(I:C)) in treating a viral infection, and that the combination exhibits a synergistic anti-viral effect. Carter anticipates the instant claims.
Regarding applicant’s assertions that Carter does not disclose the data such as presented in Fig 1, MPEP 2121(I) indicates that when the reference relied on expressly anticipates or makes obvious all the elements of the claimed invention, the reference is presumed to be operable. 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).
The rejection is maintained for at least these reasons and those previously made of record.
Claim Rejections - 35 USC § 103- maintained
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.
Claims 1-6, 8-10, 15, and 17-20 remain/are rejected under 35 U.S.C. 103 as being unpatentable over Carter (U.S. 2006/0035859- previously cited), as evidenced by Hu et al. (Nature Rev Microbiol. 19:141-154 (2021)- previously cited). The rejection is maintained from the office action mailed 5/14/2026, but has been amended to reflect claims filed 8/11/2026.
Carter discloses treatment of a severe acute respiratory syndrome (SARS) virus comprising administering an 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). Carter discloses that the combination has a synergistic effect (e.g., paras [0021]-[0028]).
Carter expressly states at para [0021]: It is also reported the activity of interferon can potentially be amplified by the addition of a double-stranded RNA drug, Ampligen®. While interferon up-regulates certain intracellular antiviral pathways, dsRNAs, like Ampligen®, are required to fully activate these important antiviral pathways. When interferons are combine[d] with Ampligen® synergistic antiviral and antitumor effects are seen. Moreover, Ampligen® has already shown strong antiviral activity in two separate animal models of the coronavirus (MHV-3). Carter expressly taught that a combination of an interferon and Ampligen exhibited a synergistic anti-viral effect against HIV (para [0022]). Examiner notes that HIV is an RNA virus.
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. The skilled artisan would have had a reasonable expectation that administering a combination of would further yield a synergistic effect. Carter expressly taught that when interferons are combine[d] with Ampligen® synergistic antiviral effects are seen (para [0021]).
Claim 20 is rendered obvious.
Claims 1-6, 8-10, 15, and 17-20 are obvious in view of the teachings of Carter and Hu.
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).
Response to Arguments
Applicant traverses the rejection at pp. 9-11. Applicant asserts that although
Carter reports synergy between interferon and Ampligen against HIV, this disclosure does not establish a reasonable expectation that the same combination would be synergistic against a coronavirus specifically. Carter itself treats its coronavirus and HIV/tumor disclosures separately, and provides no data, mechanism, or reasoning linking the synergy it observed in the HIV/tumor context to the distinct viral entry, replication, and innate-immune-evasion mechanisms of coronaviruses described in the present specification (reply at p. 10).
Applicant refers to an excerpt from the enablement rejection for the assertion that pharmaceutical and biological art is generally unpredictable (reply at p. 10). Applicant states: [A] skilled artisan would not have had a reasonable expectation that Carter's HIV/tumor synergy would extend to coronaviruses without further investigation. Id.
Applicant asserts “unexpected results” that rebut any prima facie case of obviousness. Id. Applicant asserts the specification demonstrated that combining an interferon with rintatolimod, polyI:C, or TNFa produces synergistic induction of multiple cell intrinsic antiviral effective genes specifically relevant to resistance against SARS-CoV-2 and other RNA viruses. Applicant states “because Carter does not disclose or suggest that it’s interferon/dsRNA combination is synergistic against any coronavirus, this result was not predictable from Carter and Hu, individually or in combination, and is entitled to substantial weight in providing an obviousness rejection (reply at pp 10-11P.
Examiner has reviewed and considered applicants arguments, but is not persuaded.
Examiner first notes that patents and applications are relevant as prior art for all they contain. "The use of patents as references is not limited to what the patentees describe as their own inventions or to the problems with which they are concerned. They are part of the literature of the art, relevant for all they contain." In re Heck, 699 F.2d 1331, 1332-33, 216 USPQ 1038, 1039 (Fed. Cir. 1983). A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill the art, including nonpreferred embodiments. Merck & Co. v. Biocraft Laboratories, 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989).
Carter expressly taught that a combination of an interferon and Ampligen exhibited a synergistic anti-viral effect against HIV, an RNA virus (para [0022]). Carter further stated: When interferons are combine[d] with Ampligen® synergistic antiviral … effects are seen (para [0021]). Carter further taught a combination of an interferon and a dsRNA (e.g., rintatolimod or polyI:C) for treating a SARS virus. Thus, the skilled artisan would have had a reasonable expectation of success that the combination of a interferon and Ampligen/rintatolimod would yield a synergistic antiviral effect against a SARS virus, e.g., SARS-CoV-2, as taught by Carter.
MPEP guidelines require a “reasonable” expectation of success, there is no requirement of a guarantee of success. Conclusive proof of efficacy is NOT required to show a reasonable expectation of success. Acorda Therapeutics, Inc. v. Roxane Lab., Inc., 903 F.3d 1310, 1333, 128 USPQe2d 1001, 1018 (Fed. Cir. 2018) ("This court has long rejected a requirement of ‘[c]onclusive proof of efficacy’ for obviousness." (citing to Hoffmann-La Roche Inc. v. Apotex Inc., 748 F.3d 1326, 1331 (Fed. Cir. 2014); PharmaStem Therapeutics, Inc. v. ViaCell, Inc., 491 F.3d 1342, 1364 (Fed. Cir. 2007); Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1364, 1367-68 (Fed. Cir. 2007) (reasoning that "the expectation of success need only be reasonable, not absolute")). See MPEP § 2143.02.
Examiner expressly notes that Applicant’s comment regarding the enablement rejection is taken out of context. The enablement rejection (withdrawn herein) related to previous claims that included prevention claim language. Thus, the enablement rejection related to unpredictably of preventing a viral infection.
Regarding applicants assertions of “unexpected results”, the weight attached to evidence of secondary considerations by the examiner will depend upon its relevance to the issue of obviousness and the amount and nature of the evidence. Note the great reliance apparently placed on this type of evidence by the Supreme Court in upholding the patent in United States v. Adams, 383 U.S. 39,148 USPQ 479 (1966). To be given substantial weight in the determination of obviousness or nonobviousness, evidence of secondary considerations must be relevant to the subject matter as claimed, and therefore the examiner must determine whether there is a nexus between the merits of the claimed invention and the evidence of secondary considerations. Ashland Oil, Inc. v. Delta Resins & Refractories, Inc., 776 F.2d 281, 305 n.42, 227 USPQ 657, 673-674 n. 42 (Fed. Cir. 1985), cert. denied, 475 U.S. 1017 (1986). The term “nexus” designates a factually and legally sufficient connection between the objective evidence of nonobviousness and the claimed invention so that the evidence is of probative value in the determination of nonobviousness. Demaco Corp. v. F. Von Langsdorff Licensing Ltd., 851 F.2d 1387, 7 USPQ2d 1222 (Fed. Cir.), cert. denied, 488 U.S. 956 (1988). See M.P.E.P. § 716.01(b).
As noted above in the written description rejection, the teachings of the specification are not commensurate with the scope of the instant claims. The specification is limited to specific compounds (requiring an interferon as one of the 2 compounds in the claimed combination) and sars-cov-2. Moreover, the example does not teach treatment of a virus. Instead, the example relates to gene expression as a surrogate for a viral infection.
Even if applicant did properly establish unexpected results, recent caselaw reiterated the principle from Newell Cos. v. Kenny Mfg. Co., 9 USPQ2d 1417, 1426 (Fed. Cir. 1988) that the mere presence of secondary considerations does not necessarily overcome a strong case of obviousness. See Pfizer Inc. v. Apotex Inc., 82 U.S.P.Q.2d 1321, 1338-39 (Fed. Cir. 2007) (quoting In re Chupp, 816 F.2d 643, 646 (Fed. Cir. 1987)). Secondary considerations are only one factor in determining obviousness. The cited art establishes that a combination of an interferon and Ampligen exhibits an anti-viral effect. Carter further taught administration of the compounds to a coronavirus. Thus, the antiviral effects reported by applicant for a combination of interferon and Ampligen/ rintatolimod in treating a viral infection would have been expected by one of ordinary skill in the art.
The rejection is maintained for at least these reasons and those previously made of record.
Conclusion
No claims are allowed.
Claims 1-15, and 17-20 are pending. Claims 7 and 11-14 are withdrawn.
Claims 1-6, 8-10, and 15-20 are rejected.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KRISTINA M HELLMAN whose telephone number is (571)272-2836. The examiner can normally be reached M-F 9:00 am-5:30 pm.
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/KRISTINA M HELLMAN/ Examiner, Art Unit 1654
/JULIE HA/ Primary Examiner, Art Unit 1654
