DETAILED ACTION
Notice of 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 .
Election/Restrictions
Applicant’s election without traverse of a single method in the reply filed on 7/21/2026 is acknowledged
The elected species read upon claims 1-3, 5-13, 15-18 and 22-24. Claim 14 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.
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(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.
Claim 10 is rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claim 10 recites “[a] method for treating coronavirus disease (COVID-19) in a subject”.
The inclusion of COVID-19 in parentheses renders the claim indefinite because it is unclear whether that limitation is part of the claimed invention. See MPEP § 2173.05(d).
Claim 6 is rejected under 35 U.S.C. 112(d) 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.
Claim 1 is drawn to “[a] method of treating a lung condition in a subject... comprising administering to the subject a therapeutically effective amount of vandetanib... wherein the lung condition is characterized by elevated levels of IL-6 and TNF-α... and wherein administration of the therapeutically effective amount of vandetanib reduces the elevated levels of IL-6 and TNF-α”.
Claim 6 is drawn to “[t]he method of claim 1, wherein the administration reduces a level of... IL-6... IL-10 and... TNF- α, or a combination thereof, in the subject”.
As such, claim 6 fails to further limit claim 1 since the administration of vandetanib according to claim 6 need only to reduce the level of IL-6, for example, whereas claim 1 requires the administration to reduce the levels of IL-6 and TNF- α.
Applicant may cancel the claim, amend the claim to place the claim in proper dependent form, rewrite the claim in independent form, or present a sufficient showing that the dependent claim complies with the statutory requirements.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-3, 5-13, 15-18 and 22 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Prete et al (Endocrine 72:332-339, published 2/27/2021) as evidenced by Chi et al (J Inf Dis 222:746-754, 2020).
Claim 1 is drawn to a method of treating a lung condition (more specifically, COVID-19 (claim 3)) in a subject (more specifically, a human subject (claim 5)) in need of treatment thereof, the method comprising administering to the subject a therapeutically effective amount of vandetanib or a pharmaceutically acceptable salt thereof,
wherein the lung condition is characterized by elevated levels of IL-6 and TNF-α (claims 1 and 6) and, one or more cytokines (claim 2), relative to a subject not having the lung condition; and
wherein administration of the therapeutically effective amount of vandetanib reduces the elevated levels of IL-6 and TNF-α (and, more specifically, increases a level of IFN-1β (claim 7) and/or reduces a level of CCL2, CCL3 and/or CCL4 (claims 8-9)).
Prete et al teach identification of a human patient that “was taking vandetanib for metastatic medullary thyroid cancer (MTC)” and “presented with mild COVID-19” wherein, “[a]fter a multidisciplinary consultation, we decided against discontinuation of vandetanib. After 2 months from the infection, he did not present any signs of active infection” (Abstract).
As such, Prete et al teaches administration of a therapeutically effective amount of vandetanib to a human subject suffering from COVID-19 and in need of treatment thereof.
However, Prete et al do not disclose:
(a) administering vandetanib specifically for the treatment of COVID-19;
(b) the COVID-19 in the subject being characterized by elevated levels of IL-6 and TNF-α (and, one or more cytokines) relative to a subject not having the lung condition; or
(c) reducing the elevated levels of IL-6 and TNF-α, increasing a level of IFN-1β, and reducing a level of CCL2, CCL3 and/or CCL4.
Yet, as to (a): a preamble is generally not accorded any patentable weight where it merely recites the purpose of a process, and where the body of the claim does not depend on the preamble for completeness but, instead, the process steps are able to stand alone (see In re Hirao, 535 F.2d 67 (CCPA 1976) and Kropa v. Robie, 187 F.2d 150 (CCPA 1951)).
In the instant case, the preamble (i.e., treating a lung condition (more specifically, COVID-19) in a subject (more specifically, a human subject) in need of treatment thereof) merely recites the purpose of administering a therapeutically effective amount of vandetanib to a human subject suffering from COVID-19 and in need of treatment thereof, as taught by Prete et al.
As to (b): as discussed above, Prete et al teach treatment of patient “present[ing] with mild COVID-19” (Abstract).
And, as evidenced by Chi et al, who “investigated the serum cytokine levels in... mild... SARS-CoV-2 infected cases” (Abstract), IL-6, TNF-α, and IL-1β were elevated in mild COVID-19 relative to a subject not having the lung condition (Page 750, Figure 1).
Accordingly, it is necessarily the case that the COVID-19 in the patient treated according to the method of Prete et al is characterized by elevated levels of IL-6 and TNF-α (and, one or more cytokines) relative to a subject not having the lung condition
And, as to (c): although it is recognized that “[i]nherency may not be established by probabilities or possibilities” (In re Robertson, 169 F.3d 743 (Fed. Cir. 1999)), Applicant is also reminded that the U.S. Patent Office is not equipped with analytical instruments to test prior art compositions for the infinite number of ways that a subsequent Applicant may present previously unmeasured characteristics. When, as here, the prior art appears to contain the exact same elements as those instantly claimed, the burden is properly shifted to Applicant to show otherwise. As stated in In re Best, Bolton, and Shaw, “[w]here… the claimed and prior art products are identical or substantially identical, or are produced by identical or substantially identical processes, the PTO can require an applicant to prove that the prior art products do not necessarily or inherently possess the characteristics of his claimed product" 562 F2d 1252 (CCPA 1977). In the instant case, the claimed and prior art products are identical. As such, absent evidence to the contrary, it is asserted that the administration of vandetanib to a subject suffering from COVID-19 as taught by Prete et al would necessarily reduce the elevated levels of IL-6 and TNF-α, increase a level of IFN-1β, and reduce a level of CCL2, CCL3 and/or CCL4 in said subject (see also In re Fitzgerald 619 F2d 67 (CCPA 1980): the burden is shifted to the applicants to "prove that subject matter shown to be in the prior art does not possess characteristic relied on”).
In view of all of the foregoing, claims 1-3 and 5-9 are anticipated.
Claim 10 is drawn to a method of treating COVID-19 in a subject (more specifically, a human subject (claims 12-13)) in need of treatment thereof, the method comprising administering to the subject a therapeutically effective amount of vandetanib or a pharmaceutically acceptable salt thereof,
wherein the COVID-19 in said subject is characterized by a level of one or more cytokines that are elevated compared to a subject that does not have COVID-19 (claim 11); and
wherein administration of the therapeutically effective amount of vandetanib reduces the elevated levels of IL-6, IL-10, and/or TNF-α (claim 15), increases a level of IFN-1β (claim 16), and/or reduces a level of CCL2, CCL3 and/or CCL4 (claims 17-18).
For the same reasons as discussed above regarding claims 1-3 and 5-9, claims 10-13 and 15-18 are also anticipated.
Claim 22 is drawn to the method of claim 10, wherein vandetanib is administered at a dose of about 5 mg/kg to about 50 mg/kg per day.
Prete et al teach “vandetanib treatment (200 mg/day)” (Page 334, Column 1) which equates to about 2.2 mg/kg per day to about 2.35 mg/kg per day assuming a weight of about 80 to 90 kg.
Accordingly, claim 22 is also anticipated.
Claim Rejections - 35 USC § 103
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 23-24 are rejected under 35 U.S.C. 103(a) as being unpatentable over Prete et al (Endocrine 72:332-339, published 2/27/2021) as evidenced by Chi et al (J Inf Dis 222:746-754, 2020) as applied to claims 1-3, 5-13, 15-18 and 22 above, in further view of Beigel et al (N Engl J Med 383:1813-1826, 2020).
Claims 23-24 are drawn to the method of claim 1, further comprising an antiviral agent to the subject, wherein the administration reduces mitochondrial accumulation of EGFR (claim 23), more specifically, wherein the antiviral agent comprises remdesivir (claim 24).
As discussed above, Prete et al teach administration of a therapeutically effective amount of vandetanib to a human subject suffering from COVID-19 and in need of treatment thereof.
However, Prete et al do not teach the further administration of remdesivir.
Yet, as taught by Beigel et al, “remdesivir was superior to placebo in shortening time to recovery in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection” (Abstract).
Accordingly, it would have been prima facie obvious to further administer remdesivir to the human subject suffering from COVID-19 and in need of treatment thereof treated according to the method of Prete et al. It would have been obvious to do so in an effort to shorten time to recovery and lower the risk of respiratory tract infection in said subject, with a reasonable expectation of success.
As such, claims 23-24 are rejected as prima facie obvious.
Claims 1-3, 5-13, 15-18 and 22 are ADDITIONALLY rejected under 35 U.S.C. 103(a) as being unpatentable over CN 111728973A (published 10/02/2020 based on the attached English language machine translation) as evidenced by Chi et al (J Inf Dis 222:746-754, 2020).
Claim 1 is drawn to a method of treating a lung condition (more specifically, COVID-19 (claim 3)) in a subject (more specifically, a human subject (claim 5)) in need of treatment thereof, the method comprising administering to the subject a therapeutically effective amount of vandetanib or a pharmaceutically acceptable salt thereof,
wherein the lung condition is characterized by elevated levels of IL-6 and TNF-α (claims 1 and 6) and, one or more cytokines (claim 2), relative to a subject not having the lung condition; and
wherein administration of the therapeutically effective amount of vandetanib reduces the elevated levels of IL-6 and TNF-α (and, more specifically, increases a level of IFN-1β (claim 7) and/or reduces a level of CCL2, CCL3 and/or CCL4 (claims 8-9)).
CN 111728973A teaches “a series of medicines for resisting novel coronavirus SARS-CoV-2 and application thereof” (Abstract), in particular wherein “the medicine comprises an effective amount of.... Vandetanib” listed among a total of 18 compounds (Page 2, Summary of the Invention; see also Figure 1(h)). And, as specifically taught by CN 111728973A, “the above 18 drugs... have the potential to treat COVID-19 pneumonia caused by human infection with the virus” (Page 3, Invention Effect).
Accordingly, CN 111728973A render obvious a method of treating COVID-19 in a human subject in need of treatment thereof, comprising administering to the subject a therapeutically effective amount of vandetanib.
However, CN 111728973A does not disclose:
(a) treating COVID-19 in the subject wherein the COVID-19 is characterized by elevated levels of IL-6 and TNF-α (and, one or more cytokines) relative to a subject not having the lung condition; or
(b) reducing the elevated levels of IL-6 and TNF-α, increasing a level of IFN-1β, and reducing a level of CCL2, CCL3 and/or CCL4.
Yet, as to (a): as evidenced by Chi et al, who “investigated the serum cytokine levels in... mild, moderate [and] severe... SARS-CoV-2 infected cases” (Abstract), IL-6, TNF-α, and IL-1β were elevated in all COVID-19 cases relative to a subject not having the lung condition (Page 750, Figure 1).
Accordingly, it is necessarily the case that treating COVID-19 in a subject in need thereof according to the method of CN 111728973A would entail treating COVID-19 which is characterized by elevated levels of IL-6 and TNF-α (and, one or more cytokines) relative to a subject not having the lung condition
And, as to (b): although it is recognized that “[i]nherency may not be established by probabilities or possibilities” (In re Robertson, 169 F.3d 743 (Fed. Cir. 1999)), Applicant is also reminded that the U.S. Patent Office is not equipped with analytical instruments to test prior art compositions for the infinite number of ways that a subsequent Applicant may present previously unmeasured characteristics. When, as here, the prior art appears to contain the exact same elements as those instantly claimed, the burden is properly shifted to Applicant to show otherwise. As stated in In re Best, Bolton, and Shaw, “[w]here… the claimed and prior art products are identical or substantially identical, or are produced by identical or substantially identical processes, the PTO can require an applicant to prove that the prior art products do not necessarily or inherently possess the characteristics of his claimed product" 562 F2d 1252 (CCPA 1977). In the instant case, the claimed and prior art products are identical. As such, absent evidence to the contrary, it is asserted that treating COVID-19 in a human subject in need of treatment thereof, comprising administering to the subject a therapeutically effective amount of vandetanib as taught by CN 111728973A would necessarily reduce the elevated levels of IL-6 and TNF-α, increase a level of IFN-1β, and reduce a level of CCL2, CCL3 and/or CCL4 in said subject (see also In re Fitzgerald 619 F2d 67 (CCPA 1980): the burden is shifted to the applicants to "prove that subject matter shown to be in the prior art does not possess characteristic relied on”).
In view of all of the foregoing, claims 1-3 and 5-9 are rejected as prima facie obvious.
Claim 10 is drawn to a method of treating COVID-19 in a subject (more specifically, a human subject (claims 12-13)) in need of treatment thereof, the method comprising administering to the subject a therapeutically effective amount of vandetanib or a pharmaceutically acceptable salt thereof,
wherein the COVID-19 in said subject is characterized by a level of one or more cytokines that are elevated compared to a subject that does not have COVID-19 (claim 11); and
wherein administration of the therapeutically effective amount of vandetanib reduces the elevated levels of IL-6, IL-10, and/or TNF-α (claim 15), increases a level of IFN-1β (claim 16), and/or reduces a level of CCL2, CCL3 and/or CCL4 (claims 17-18).
For the same reasons as discussed above regarding claims 1-3 and 5-9, claims 10-13 and 15-18 are also rejected as prima facie obvious.
Claim 22 is drawn to the method of claim 10, wherein vandetanib is administered at a dose of about 5 mg/kg to about 50 mg/kg per day.
As stated by MPEP 2144.05, “[g]enerally, 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” (see also In re Aller (220 F.2d 454 (CCPA): “where 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 fact, as further discussed by the court, “[s]uch experimentation is no more than the application of the expected skill of the [ordinarily skilled artisan] and failure to perform such experiments would, in our opinion, show a want of the expected skill”; see also In re Peterson, 315 F.3d at 1325 (Fed. Cir. 2005): “[t]he 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” and “[o]nly if the ‘results of optimizing a variable’ are ‘unexpectedly good’ can a patent be obtained for the claimed critical range” (quoting In re Antonie (559 F.2d 618 (CCPA 1977))).
In the instant case, the dose of active ingredient to be administered for the treatment of a condition is clearly a result-effective variable. Indeed, as indicated by the court in Ariosa Diagnostics, Inc. v. Sequenom, Inc., 809 F.3d 1282, 1293 (Fed. Cir. 2015), every ordinary artisan in medicine performs “merely routine optimization of drug dosage to maximize therapeutic effect.” Accordingly, it would have been customary for an artisan of ordinary skill in the art to determine the optimal dose of vandetanib to administer in order to best achieve the desired results.
As such, claim 22 is also rejected as prima facie obvious.
Claims 23-24 are ADDITIONALLY rejected under 35 U.S.C. 103(a) as being unpatentable over CN 111728973A (published 10/02/2020 based on the attached English language machine translation) as evidenced by Chi et al (J Inf Dis 222:746-754, 2020) as applied to claims 1-3, 5-13, 15-18 and 22 above, in further view of Beigel et al (N Engl J Med 383:1813-1826, 2020).
Claims 23-24 are drawn to the method of claim 1, further comprising an antiviral agent to the subject, wherein the administration reduces mitochondrial accumulation of EGFR (claim 23), more specifically, wherein the antiviral agent comprises remdesivir (claim 24).
As discussed above, CN 111728973A teaches administration of a therapeutically effective amount of vandetanib to a human subject suffering from COVID-19 and in need of treatment thereof.
However, CN 111728973A do not teach the further administration of remdesivir.
Yet, as taught by Beigel et al, “remdesivir was superior to placebo in shortening time to recovery in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection” (Abstract).
Accordingly, it would have been prima facie obvious to administer remdesivir along with vandetanib for the treatment of COVID-19. As stated in MPEP 2144.06, “[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose… [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846 (CCPA 1980).
As such, claims 23-24 are also rejected as prima facie obvious.
Conclusion
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/CRAIG D RICCI/Primary Examiner, Art Unit 1611
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