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 .
Please note the Examiner for this Application has CHANGED.
The Applicants’ Amendment to the Claims filed on May 12, 2026 is entered.
Claims 2 and 17 are cancelled.
Claims 21-23 are new.
Claims 1, 3-16, and 18-23 are pending and under examination.
Priority
This US Application 18/222,784 filed on 07/17/2023 is a CIP of 17/890,754 filed on 08/18/2022 and claims US priority benefit of US 63/396,040 filed on 08/08/2022, 63/308,782 filed on 02/10/2022, 63/294,067 filed on 12/27/2021, US 17/472,604 filed on 09/11/2021 (now US Patent 12226431), 63/235,772 filed on 08/22/2021, 63/235,772 filed on 08/22/2021, 17/207,250 filed on 03/19/2021, 63/029,458 filed on 05/23/2020 and 63/019,312 filed on 05/02/2020. The priority documents of 17/890,754, 63/308,782, and US 17/472,604 do not disclose the element of nanobody. Thus, present claims receive an effective filing date of 08/08/2022 (US63/396,040).
Response to Amendment
Any/all objections and rejections made in the previous office action and not repeated in this office action are withdrawn in view of the Applicants’ Amendment to the Claims filed on May 12, 2026.
Claim Objections – new grounds
Currently amended claims 1, 9, 12, and 14 are objected to because of the following informalities:
Claims 1 and 12 lack units for the % concentration values. Appropriate correction is required.
Claim 9 appears to contain a typographical error in omitting a period at the end of the sentence. The claim is being objected to rather than rejected for being indefinite because the claim has been construed on the record as being a clear, complete sentence and thus the missing period is construed to be a typographical error. Appropriate correction is required.
Independent claim 12, line 7, recites “wherein the solution is either citrate buffered at a pH of 2.5 or phosphate buffered at a pH of 7.5”. Although the claim does not explicitly recite the term solution prior to the term “the solution”, the claim is being construed to intend that the composition is a solution because it recites units in ug per mL. For improved clarity, the claim should clarify that the composition is a solution. Appropriate correction is required.
Currently amended claim 14 is objected to because it depends from claim 16 which is not a claim previously set forth. Claim 14 does not meet the first prong of 35 U.S.C. 112(d) which is that the claim shall contain a reference to a claim previously set forth. See 35 U.S.C. 112(d) which recites: … a claim in dependent form shall contain a reference to a claim previously set forth… Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
New claims 21-22 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Newly added claims 21 and 22 each fail to include all the limitations of the claim upon which it depends. This is new grounds necessitated by amendment.
Regarding claim 21, the claim recites that the nanobody is engineered to attach to SARS-CoV-2, influenza, or HIV/AIDS, or alternatively to a host cell virus binding receptor. However, claim 21 depends from claim 1 which already requires that the nanobody is engineered to bind to a targeted antigen of an enveloped virus.
Regarding claim 22, the claim recites that the nanobody is engineered to attach to a coronavirus spike protein or alternatively to an ACE2 host cell receptor for the enveloped virus. However, claim 22 depends from claim 1 which already requires that the nanobody is engineered to bind to a targeted antigen of an enveloped virus.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Indefinite - new grounds necessitated by amendment.
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.
Claims 5-6 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.
Claim 5 recites that the nanobody is engineered to attach to a host cell receptor. Claim 6 specifies within claim 5 that the host cell receptor is ACE2. However, the base claim 1 is presently amended to require that the nanobody is engineered to bind to a targeted antigen of an enveloped virus (rather than to a host cell receptor). The scope of claims 5-6 is now unclear because it is unclear how the nanobody would be engineered to bind to both a viral antigen and a host cell receptor.
Written Description – updated for amendment
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.
Currently amended claims 1, 3-16, and 18-23 are rejected under 35 U.S.C. 112(a) 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.
Presently amended claims 1, 3-11, 15, and 21-22 are drawn to a composition comprising:
a nanobody engineered to bind to a targeted antigen of an enveloped virus; a cyclodextrin at a concentration between 1-10%; a zinc ionophore at a concentration between 8-24 µg mL-1; a zinc-containing compound; and, benzalkonium.
Presently amended claims 12-13, are drawn to a composition comprising:
a nanobody engineered to attach to a host cell membrane protein; HPβCD at a concentration of 1-10%; quercetin at a concentration of 8-24 µg mL-1; zinc chloride; and,
benzalkonium chloride; wherein the solution is either citrate buffered at a pH of 2.5 or phosphate buffered at a pH of 7.5; wherein the host cell membrane protein is a virus binding protein.
Presently amended claims 14, 16, 18-20, and 23 are drawn to a method of treating a subject at risk of contracting a viral infection involving an enveloped virus, the method comprising the step of: administering to the subject a composition comprising:
a nanobody engineered to attach to a surface protein of the virus, a cyclodextrin at a concentration between 1-10%, a zinc ionophore at a concentration between 8-24 µg mL-1, a zinc-containing compound, and benzalkonium; wherein the virus is involved in binding to a host cell plasma membrane or to a host cell receptor.
Thus, all claims requires the critically essential element of a nanobody engineered to attach to a surface protein/targeted antigen of an enveloped virus (claims 1 and 16) or engineered to attach to a host cell membrane protein (claim 12).
However, the specification does not provide a representative set of species of such nanobody structures correlated to the required binding functions to fulfill the requirements of written description with regard to the broad genus of nanobodies encompassed the claims. The specification provides no nanobody structures but rather refers to nanobodies as engineered against a generic viral protein or specifically against a spike protein of SARS-CoV-2 or against a host cell receptor such as the ACE2 receptor. (See para 0003; 0010; 20-23.)
The specification discloses embodiments of certain nanobodies engineered to attach to viral targets broadly, including the SARS-CoV-2 virus, influenza, HIV, as well nanobodies engineered to attach to a species of a host cell surface receptor, being an ACE2 receptor. However, the specification does not provide a representative set of such functional species of nanobodies to represent the vast genus of nanobodies encompassed by the claims as presently written.
Further, the state of the art before the effective filing date of the presently claimed invention shows that the correlation of nanobody structure to their function was unpredictable. According to Hacisuleyman et al ("ModiBodies: A computational method for modifying nanobodies to improve their antigen binding and specificity," bioRxiv, October 2019; of record), therapeutic nanobodies, are highly specific and require precise targets to attach to (see Abstract).
Applicant has only recited embodiments of nanobodies engineered to attach to specific viral targets and the host surface, namely the spike protein of SARS- CoV-2 and the ACE2 receptor. Beyond these embodiments the disclosure mentions using the composition to treat other enveloped viral infections, including influenza and HIV, but no specific targets on the host cells or on the viruses themselves are elucidated. Further, one of ordinary skill in the art cannot predict the structure of a functional nanobody by defining the antigen to which it binds. Rather, the structure of the nanobody must be envisioned to satisfy the written description requirement. Adequate written description requires more than a mere statement that a compound is part of the invention and reference to a potential method of isolating a compound. 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.
As such, Applicant has not fulfilled the requirements of written description with regard to the broad genus of nanobodies.
Response to Argument
The Applicants’ arguments filed on May 12, 2026 have been fully considered but are unpersuasive. The applicants argue that claim 1 is presently amended to recite that the nanobody is “engineered to bind to a targeted antigen of an enveloped virus” and that such “are well known to the skilled person in the art”, further arguing that “[n]anobodies engineered to bind to targeted antigens of the enveloped viruses SARS-CoV-2, influenza, and HIV/AIDS are well known to the skilled person in the art”.
In addition, the applicants argue:
In relation to new claims 21-23, specific examples of enveloped viruses, "wherein the nanobody is engineered to attach to SARS-CoV-2, influenza, or HIV/AIDS viruses, or to a host cell receptor" (claim 21), and "wherein the nanobody is engineered to a coronavirus spike protein or to an ACE2 host cell receptor" (claims 22-23) are disclosed on p. 6, par.[0018] (SARS-CoV-2, influenza and HIV/AIDS); p. 6, par. [0021] (SARS-CoV-2 spike protein and ACE2 receptor); and p. 8, par. [0027] (SARS-CoV-2, influenza and HIV/AIDS), of the Specification. These disclosures are a "constructive reduction to practice". According to MPEP § 2128.05:
Reduction to practice may be an actual reduction or a constructive reduction to practice which occurs when a patent application on the claimed invention is filed. The filing of a patent application serves as conception and constructive reduction to practice of the subject matter described in the application. Thus, the inventor need not provide evidence of either conception or actual reduction to practice when relying on the content of the patent application. Hyatt v. Boone, 146 F.3d 1348, 1352, 47 USPQ2d 1128, 1130 (Fed. Cir.1998).
However, this argument is unpersuasive because it is a conclusory argument without evidence. Generally, arguments of counsel cannot take the place of evidence on the record. Further, the applicants’ arguments have not addressed the rejection regarding claims 12-13 which are drawn to a composition comprising: a nanobody engineered to attach to a host cell membrane protein (rather than to a viral protein).
In addition, this argument is unpersuasive because the structure of the nanobody must be envisioned to satisfy the written description requirement. It is generally considered that a skilled artisan cannot predict the structure of a functional nanobody by defining the antigen to which it binds. The applicants have not shown possession of the vast genus of functional nanobodies embodied by the presently claimed invention. Adequate written description requires more than a mere statement that a compound is part of the invention and reference to a potential method of isolating a compound. 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.
Claim Rejections - 35 USC § 103 – new grounds necessitated by amendment
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.
Presently amended claims 1, 3-16, and 18-23 are rejected under 35 U.S.C. 103 as being unpatentable over Sommer et al (US Patent 11,045,434B1; pub June 2021, filed 11/2020), in view of Panchariya et al (“Zinc2+ ion inhibits SARS-CoV-2 main protease and viral replication in vitro” ChemComm., Aug 27 2021), in view of Peyman et al (US 20220202933; of record), as evidenced by Lan et al in "Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor." (Nature vol. 581,7807 β pages 215-220; of record).
Regarding base claims 1, 12, and 16, Sommer et al discloses a method of treating a viral infection caused by or associated with SARS-CoV-2 in a subject, by administering a therapeutically effective amount of a formulation the antiviral niclosamide and cyclodextrin. Sommer et al show reducing the viral load of SARS-CoV-2 by administering a composition comprising, a cyclodextrin at 5-10%, including the preferred embodiment of hydroxypropyl-beta-cyclodextrin at 5-10% (aka HPβCD). (See col 25, lines 3-15; col. 27, lines 49-50.) Sommer et al discloses that the composition may further comprise a preservative, specifically benzalkonium chloride at 0.002-0.15%. (See col 7, lines 63-67.) In addition, Sommer et al discloses that the composition may comprise chelators, including zinc (see col. 26, line 9), and phosphate buffers (see col 8, lines 4-12) for a pH of 7.5 to 7.8 (see col 8, lines 38-39).
Regarding claim 9, Sommers et al teach an embodiment of the composition is buffered at a pH of 7.5 to 7.8 (see col 8, lines 38-39).
Regarding claim 10, Sommers et al disclose the preferred embodiment of HPβCD at 5-10%. (See col 25, lines 3-15; col. 27, lines 49-50.)
Regarding claims 11 and 13, Sommer et al discloses that the composition is atomized and is suitable for administration to the airways of a subject. (See Abstract stating the formulation is for intraoral or intranasal inhalation.) Further, Peyman et al (below) also disclose that their antiviral composition is aerosolized or nebulized, a type of atomization, and administered nasally (see para 0045 to 0047).
Regarding claim 15, Sommer et al discloses that their antiviral composition is suspended in an aqueous solution (see para 0028). Further, Peyman et al (below) teach many embodiments wherein the vaccine, antivirals, or vaccine cocktails are in a saline or physiological solution, both of which are inherently aqueous (see para 0077, 0170, 0181, 0182, 0192, 0500). Peyman provide a motivation for using an aqueous solution, specifically a saline solution, because of its usefulness in passing through the stomach to release medication locally and its ability to damage the invading viruses in the mucosa (see 0052, 0053).
However, regarding base claims 1, 12, 16, and dependent claim 20, Sommer et al does not teach the composition comprising a zinc ionophore, specifically quercetin at a concentration of 8-24 µg/mL, nor that the zinc compound is specifically zinc chloride.
Panchariya et al teaches a composition for inhibiting replication of SARS-CoV-2, comprising zinc salts, including zinc chloride, in combination with the zinc ionophore, quercetin. (See entire article; Figures 1c and 2c.) Panchariya et al discloses the concentration range of quercetin at 0.01-100 µM, which is equivalent to 0.003-30 µ/mL quercetin. (See Figure 2c.)
Regarding claims 7 and 20, Panchariya et al discloses that the zinc ionophore quercetin in their antiviral cocktail. (See entire article; Figures 1c and 2c.)
The level of skill in the art was high before the effective filing date of the presently claimed invention.
One would be motivated to combine a zinc salt, specifically zinc chloride with a zinc ionophore, specifically quercetin, in the composition/method of Sommer, because Panchariya et teaches that the combination results in 10% increase in intracellular zinc concentration and results in effective inhibition of SARS-CoV-2 viral replication. With respect to the claimed concentrations of components, the ranges overlap that of the prior art. 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). (MPEP § 2144.05(I)) Moreover, 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). (MPEP § 2144.05(II)) "The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages." In re Peterson, 315 F.3d 1325, 1330, 65 USPQ2d 1379, 1382-83 (Fed. Cir. 2003).
It would have been obvious to one of ordinary skill in the art to combine the elements of the quercetin and zinc chloride to an antiviral composition as shown in Sommer et al because both references are in the art of treating/reducing a SARS-CoV-2 infection. Panchariya et al show that zinc not only inhibits the SARS-CoV-2 main protease with nano-molar affinity, but also viral replication (see Abstract). Specifically using zinc chloride, they showed complete inhibition of the protease at 6.25 µM (see Fig 1c). Further, Panchariya et al show that the natural ionophore quercetin increase the anti-viral potency of Zn2+.
Also, regarding instant claim 8, although Panchariya et al does not teach the specific concentration of quercetin is at a concentration of 8 µg/mL; or that the specific concentration of the zinc chloride is at a concentration of 1 mg/mL, these values would be prima facie obvious over Panchariya et al because Panchariya et al discloses the concentration range of quercetin at 0.01-100 µM, which is equivalent to 0.003-30 µg/mL quercetin. (See Figure 2c.) Panchariya et al show using zinc chloride at various concentration, and show complete inhibition of the SARS-CoV-2 protease at 6.25 µM (see Fig 1c). Note that 6.25 µM of zinc chloride has a concentration of about 0.852 mg/L which is construed to meet the limitation of 1mg/L.
In addition, regarding claims 1, 3-16, and 18-23, Sommer et al differs from the present claims as it does not disclose a nanobody against either the ACE2 cell membrane receptor for the SARS-CoV-2 spike protein or against the SARS-CoV-2 spike protein itself in their antiviral compositions for treating a subject at risk of contracting a viral infection, including the SARS-CoV-2 coronavirus.
Peyman et al teach a vaccine composition/cocktail for treating viral infections (see 0067) including a nanobody. Also, Peyman et al teach a method of treating a subject at risk of contracting a viral infection, caused by an enveloped virus, namely coronaviruses (see para 0145 to 0148). Peyman et al disclose the nanobodies are capable of binding viral or cellular targets (see 0544). Specifically, Peyman teach the use of nanobodies to attach to the RBD or ACE2 host cell receptor (see 0544). Peyman teach an embodiment with nanobodies obtained from llamas and alpacas to attach to the RBD-ACE2, or multiple antibodies to spike proteins or the use of ACE2 decoys or administered together with a known antiviral such as remdesivir (see 0544). Peyman et al disclose that the RBD is the receptor binding domain of the virus that attaches to the ACE2 of the host receptor and causes the binding of the virus to the cell (see 0012, 0013, and 0544). Peyman et al disclose that "the virus" is a coronavirus (see 0012, 0013). As such, Peyman et al disclose the nanobodies as binding the RBD of the coronavirus, which, as evidenced by Lan et al, is the spike protein that mediates binding to the ACE2 of the host cell (see Lan et al; Abstract; entire article).
Regarding claims 1, 3-4, 16, 18-19 and 21-23, Peyman et al teaches the coronavirus viral spike protein of SARS-CoV-2. Peyman et al teach the nanobodies as binding the RBD of the coronavirus, which, as evidenced by Lan et al, is the spike protein that mediates binding to the ACE2 of the host cell (see Lan et al Abstract).
Regarding claims 5-6, 12, 18-19, and 21-22, Peyman et al discloses the nanobodies to attach to the ACE2 host cell receptor (see 0544).
Also, regarding claim 14, the combination of cited references do not teach that the administration of the composition occurs in two steps, wherein the nanobody and cyclodextrin is first administered and the quercetin and zinc is administered second.
One of ordinary skill in the art would have been motivated to include a nanobody against either the ACE2 cell membrane receptor for the SARS-CoV-2 spike protein or against the SARS-CoV-2 spike protein itself for the rationale of either blocking the virus binding to the cells or blocking the virus directly. The antiviral nanobody could be in addition to the antiviral niclosamide of Sommer et al for the rationale of increasing the antiviral property or substituted for the antiviral niclosamide of Sommer et al for the rationale of reducing toxicity to the subject. Regarding claim 14, one of ordinary skill in the art would have been motivated to first administer the nanobody and cyclodextrin followed by administration of quercetin and zinc for the rationale of first preventing viral attachment to cell receptors and then preventing/inhibiting viral replication and protease activity. For example, Panchariya et al disclose that both quercetin and zinc inhibit viral protease and replication whereas Peyman et al disclose that each of the elements of a nanobody and cyclodextrin have a role in preventing the viral attachment to cell receptors.
It would have been obvious to combine the elements of Sommers et al, Panchariya et al, and Peyman et al because each of these references are in the field of making and using anti-viral compositions for reducing SARS-CoV-2 infection/activity. Further, Peyman et al include many of the same components of the present claims, including quercetin (see 0243), zinc for its antiviral properties (see 0376), benzalkonium for its ability to produce a strong immune response (see 0192), and cyclodextrin for its role in preventing the viral attachment to cell receptors (see para 0338, 0340).
In view of the high skill level in the art it is considered that one of ordinary skill in the art having the cited references before the effective filing date of the presently claimed invention would have had a reasonable expectation of success to combine the antiviral components of the Sommers et al antiviral composition with the antiviral elements of Panchariya et al, and Peyman et al to arrive at the presently claimed invention.
Thus, the claims as a whole are rendered obvious over the combination of references.
Response to Argument
The Applicants’ arguments filed on May 12, 2026 regarding the prior art rejections have been fully considered but are unpersuasive as they may relate to this new grounds of rejection for reasons provided in the body of the rejection and the following. First, regarding the argument that Peyman and Lan do not teach a cyclodextrin at a concentration between 1-10%, Sommers discloses a cyclodextrin at 5-10%, including the preferred embodiment of hydroxypropyl-beta-cyclodextrin at 5-10% (aka HPβCD). Also, the argument regarding the zinc ionophore at concentration between 8-24 ug/mL is unpersuasive because Panchariya et al discloses the concentration range of quercetin at 0.01-100 µM, which is equivalent to 0.003-30 µg/mL quercetin. (See Figure 2c.)
Double Patenting – updated for amendment
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 1, 3-16, and 18-23 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 10-17, 20-26, and 29-35 of U.S. Patent No. 12,226,431, in view of Peyman et al (above).
Regarding instant claims 1, and 3-6, patented claims recite a composition for administration to a subject, for inhibiting viral entry and replication of an enveloped virus in cells of the subject, consisting of: 1-5% cyclodextrin; a zinc ionophore; a zinc-containing compound; a preservative; and, an aqueous buffer where the preservative is 0.01% benzalkonium chloride (see claims 10 and 14). Regarding instant claims 3-6, patented claims recite an antiviral composition comprising 1-5% cyclodextrin, quercetin, zinc chloride, benzalkonium, and an aqueous buffer (see claims 10-12 and 14).
However, patented claims do not recite the use of a nanobody in the composition.
Peyman et al teach the use of nanobodies obtained from llamas and alpacas to attach to the RBD-ACE2, or multiple antibodies to spike proteins or the use of ACE2 decoys or administered together with a known antiviral such as remdesivir, etc. and anti-inflammatory pathway inhibitors and Ceapin-A7 and KIRA8 or spermidine to strengthen the immune response (see [0544]). Given this motivation of strengthening immune response in the subject, it would have been obvious too one having ordinary skill in the art prior to the effective filing date of then instant application to combine the patented claims and Peyman et al to make a composition containing the components discussed above. Note that the RBD is the receptor binding domain of the virus that attaches to the ACE2 of the host receptor and causes the binding of the virus to the cell (see [0012], [0013], and [0544]). In the context of this invention, the basis of "the virus" is a coronavirus (see [0012], [0013]). As such, Peyman teach the nanobodies as binding the RBD of the coronavirus, which is the spike protein, the protein that mediates binding to the host. Regarding instant claims 5 and 6, Peyman et al teach nanobodies obtained from llamas and alpacas to attach to the RBD-ACE2, or multiple antibodies to spike proteins or the use of ACE2 decoys or administered together with a known antiviral such as remdesivir (see [0544]). The ACE2 receptor is the host cell receptor involved in the binding of the virus.
Regarding instant claim 7, patented claims recite the zinc ionophore is quercetin (see claim 12).
Regarding instant claim 8, patented claims recite that the quercetin is at a concentration of 8 ug mL-1; and the zinc is zinc chloride and is at a concentration of 1 mg mL-1 (see claim 13).
Regarding instant claim 9, patented claims recite that the composition is citrate buffered at a pH of 2.5 (see claim 15) and that the composition is phosphate buffered at pH 7.5 and the preservative is 0.01% benzalkonium chloride (see claim 16).
Regarding instant claim 10, patented claims recite a composition for administration to a subject, for inhibiting viral entry and replication of an enveloped virus in cells of the subject, consisting of: 2- hydroxypropyl-ßCD; quercetin; a zinc-containing compound; a preservative; and, an aqueous buffer (see claim 35).
Regarding instant claims 11 and 13, patented claims recite the composition is administered as an inhalation or an aerosol spray (see claim 17). Given that aerosolization implies atomization, patented claims are construed to meet the limitation of atomization.
Regarding instant claim 12, patented claims recite HPBCD but do not recite wherein the HPBCD is at a concentration between 1- 10%. Patented claims also recite that the cyclodextrin is at a concentration of 1-5% (see claim 10). 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) (The prior art taught carbon monoxide concentrations of "about 1-5%" while the claim was limited to "more than 5%." The court held that "about 1-5%" allowed for concentrations slightly above 5% thus the ranges overlapped. As such, the range of 1-10% and 1-5% clearly overlap, and a case of obviousness exists on account of this overlap. Further, patented claims recite 1-5% cyclodextrin and also specify that hydropropyl-RCD is a cyclodextrin. Thus, it would be prima facie obvious to use the cyclodextrin species of 2-hydroxypropyl-BCD at 1-5% with a reasonable expectation of success.
Regarding instant claim 15, patented claims recite a method of treating a subject at risk of contracting a viral infection, caused by an enveloped virus, the method comprising the step of: administering to the subject a first composition consisting of 1-5% cyclodextrin, a preservative, and an aqueous buffer; and, administering separately, or coadministering, a second composition consisting of quercetin, a zinc- containing compound, a preservative, and an aqueous buffer (see claim 29).
Regarding instant claims 16, 14, 18, 19, 20, and 21-23 patented claims recite a method of treating a subject at risk of contracting a viral infection, caused by an enveloped virus, the method comprising the step of: administering to the subject a first composition consisting of 1-5% cyclodextrin, a preservative, and an aqueous buffer; and, administering separately, or coadministering, a second composition consisting of quercetin, a zinc- containing compound, a preservative, and an aqueous buffer (see claim 20). Regarding instant claim 14, patented claims recite a method of treating a subject at risk of contracting a viral infection, caused by an enveloped virus, the method comprising the step of: administering to the subject a first composition consisting of 1-5% cyclodextrin, a preservative, and an aqueous buffer; and, administering separately, or co-administering, a second composition consisting of quercetin, a zinc- containing compound, a preservative, and an aqueous buffer (see claim 29).
Regarding instant claims 18, 19, 20, and 21-23, patented claims recite an antiviral composition and method of composition comprising 1-5% cyclodextrin, quercetin, zinc chloride, benzalkonium, and an aqueous buffer (see claims 10-12 and 14).
Regarding instant claim 20, patented claims recite that the zinc ionophore is quercetin (see claim 12).
However, patented claims do not recite the use of a nanobody in the composition.
Peyman et al teach an antiviral composition comprising nanobodies obtained from llamas and alpacas to attach to the RBD-ACE2, or multiple antibodies to spike proteins or the use of ACE2 decoys or administered together with a known antiviral such as remdesivir (see [0544]). Peyman teach the use of nanobodies to attach to the RBD or ACE2 (see [0544]). In the context of the invention of Peyman, the RBD is the receptor binding domain of the virus that attaches to the ACE2 of the host receptor and causes the binding of the virus to the cell (see [0012], [0013], and [0544]). In the context of this invention, the basis of "the virus" is a coronavirus (see [0012], [0013]). As such, Peyman et al teach the nanobodies as binding the RBD of the coronavirus, which is the spike protein, the protein that mediates binding to the host.
Response to Arguments regarding NSDP rejections
The Applicants response regarding NSDP rejections has been fully considered but is unpersuasive regarding the rejection over U.S. Patent No. 12,226,431, in view of Peyman et al. The applicants argue:
As the present application has not been allowed, the claims are not in final form. It therefore not possible to make any determination as to double patenting or obviousness at this time. Applicant respectfully requests that this rejection be held in abeyance at least until the present claims are otherwise allowable do a proper analysis of double patenting can be made. See MPEP § 804.01.I(B)(1).
Because this argument does not point out any reasons why the rejection is not proper it is not a proper argument and the rejection is maintained.
Conclusion
No claim is allowed.
Mitzikovsky et al (WO 2021/184070 A1, filed March 2021, IDS). Mitzikovsky et al teach compositions for treating coronavirus using zinc chloride.
Foo et al ("Combating Coronavirus: Key Role of Cyclodextrins in Treatment and Prevention," Roquette, February 2020; of record). Foo et al teach that the antiviral HPβCD is useful in combating coronaviruses because it has high water solubility and an excellent safety profile (see page 1, paragraph 6). As an adjuvant, HPβCD induces helper T-cell response, enhances antigen-specific antibody titers, and maintains longer immune response, while limiting immunoglobulin E production (see page 2, paragraph 3). Foo et al. note that the concentration of HPβCD affects its virucidal function and is relevant to its safety (see page 2, paragraph 1 and page 3, paragraph 2). As such, the concentration of HPβCD in the composition is a result-effective variable, and the presence of a known result-effective variable is a motivation for a person of ordinary skill in the art to experiment to reach another workable product or process.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 CATHERINE S HIBBERT whose telephone number is (571)270-3053. The examiner can normally be reached M-F 8:00-5:00.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Melissa Fisher can be reached at 571-270-7430. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
CATHERINE S. HIBBERT
Primary Examiner
Art Unit 1658
/CATHERINE S HIBBERT/Primary Examiner, Art Unit 1658
Prosecution Insights