DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
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 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.
Election/Restrictions
Applicant's election with traverse of Group I, Interferon-beta, aerosol and vaccinated. as previously acknowledged. After further consideration, the species election requirement regarding the patient population is withdrawn and claim 10-13,16, 18-19 are rejoined.
As indicated previously, during the search, art was found for interferon-alpha. Therefore, the claim including interferon-alpha (non-elected species) was rejoined.
In the reply filed 5/22/23, Applicants amended claims 1, 8-9, 15, 17, 21-23, 36-37 and added New claim 38. Claims 2-7, 14, and 20 were cancelled.
In the reply filed 3/29/24, Applicants amended claims 1, 21-22, 35 and 38.
In the reply filed 12/17/24, Applicants amended claims 1, 35 and 38.
In the reply filed 7/24/25, Applicants amended claims 1, 10-16 and 18-19 were amended.
Claims 1, 8-13, 15-19, 21-38 are pending.
Claims 24-34 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected group, there being no allowable generic or linking claim.
Claims 1, 8-13, 15-19, 21-23 and 35-38 read on elected Group I and are under consideration.
Priority-Maintained
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 120 as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994)
The disclosure of the prior-filed provisional applications, Application No. 63/062,726, 63/076,103, 63/086,427, fail to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. The provisional Applications above do not provide support for inhibiting coronavirus in a vaccinated person, patients that tested positive for Delta variant of COVID-19 and a variant of COVID-19 that has a mutation in the spike protein. Accordingly, claims 17 and 35-37 are not entitled to the benefit of the prior applications.
Claim Interpretation
Claim 1 is drawn to a method of inhibiting coronavirus infection caused by COVID-19 comprising administering interferon-beta as an aerosol to at least a portion of the upper respiratory tract of a person at risk of being exposed to the coronavirus, COVID-19. Claim 1 requires the person is “at risk” of being exposed to a coronavirus. Therefore, the patient population does not have coronavirus, but is “at risk” of being exposed to it.
Claim 35 is drawn to a method of inhibiting coronavirus COVID-19 infection comprising administering interferon-beta as an aerosol to at least a portion of the upper respiratory tract of a person vaccinated against COVID-19, wherein said person is at risk of infection by a variant of COVID-19. Claim 35 requires the person is “at risk” of infection by a COVID-19 variant. Therefore, the patient population cannot be infected with the variant, but is “at risk” of being infected by it.
Claim Objections-Withdrawn
The objection to claims 1, 10-13, 16 and 18-19 is withdrawn due to amendment of the claims.
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.
The rejection of claims 1, 8-13, 15-19, 21-23 and 35-38 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement is maintained. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
As stated in MPEP 2164.01(a), “there are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue.”
The factors to be considered when determining whether a disclosure meets the enablement requirement of 35 USC 112, first paragraph, were described in In re Wands, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988) as:
1. the nature of the invention;
2. the breadth of the claims;
3. the state of the prior art;
4. the relative skill of those in the art;
5. the predictability or unpredictability of the art;
6. the amount of direction or guidance presented [by the inventor];
7. the presence or absence of working examples; and
8. the quantity of experimentation necessary [to make and/or use the invention.
(1) The Nature of the Invention
Claim 1 is drawn to a method of inhibiting COVID-19 infection comprising administering interferon-beta as an aerosol to the upper respiratory tract of a person at risk of being exposed to COVID-19. Claim 35 is drawn to a method of inhibiting COVID-19 infection comprising administering interferon-beta to the upper respiratory tract of a person vaccinated against COVID-19, wherein said person is at risk of infection by a variant of COVID-19. Claim 38 is drawn to a method of inhibiting COVID-19 infection comprising administering medication consisting of interferon-beta as an aerosol to the upper respiratory tract of a person at risk of being exposed to COVID-19, said person not yet infected with COVID-19.
(2) The Breadth of the claims
The claims will be given its broadest reasonable interpretation. The applicable rule for interpreting the claims is that “each claim must be separately analyzed and given its broadest reasonable interpretation in light of and consistent with the written description.” See MPEP 2163(II)(1), citing In re Morris, 127 F.3d 1048, 1053-1054; 44 USPQ2d 1023, 1027 (Fed. Cir. 1997). In view of this rule,. Claims 1 and 38 require the person is “at risk” of being exposed to a coronavirus. Therefore, the patient population does not have coronavirus, but is “at risk” of being exposed to it. Claims 35 requires the person is “at risk” of infection by a COVID-19 variant. Therefore, the patient population cannot be infected with the variant, but is “at risk” of being infected by it.
(3) The state of the prior art and (5) The predictability or unpredictability of the art
The instant application and prior art are not enabling for inhibiting COVID-19.
Sallard et al. (“Type I interferons as a potential treatment against COVID-19” Antiviral Research 178 (March 2020) 104791, previously cited) reviews the evidence to support the evaluation of IFN-1 in the treatment on coronaviruses and to discuss its potential in SARS-CoV-2 (p. 1, 2nd para.). Sallard et al. teach IFN-1 designate a group of cytokines comprising the ubiquitous alpha and beta subtypes. Sallard et al. teach they are among the first cytokines producing during a viral infection (p. 1, 1st col.). Sallard et al. teach that MERS and SARS are coronaviruses closely linked with SARS-Co-V and presenting similar properties, despite differences in their epidemiology, pathology and in several of their proteins (p. 1, bottom of 2nd col.). Sallard et al. teach that IFN alpha and beta were systemically relatively efficient in vitro and succeeded in certain animal models (p. 2, 1st col, 1st para.). Sallard et al. it has been repeatedly shown that IFN-beta is the more potent inhibitor of coronaviruses compared to IFN-alpha. Sallard et al. teach that IFN-beta appears to be the most relevant interferon to treat coronavirus infections. Sallard et al. teach that it has been suggested from in vitro studies in mice that the timing of IFN administration plays a crucial role: positive effects were observed if IFN was administered shortly after infection, but failed to inhibit viral replication and have side effects when administered later (p. 2, 1st col., 1st par). Sallard et al. teach that IFN-1 might be a safe and efficient treatment against SARS-CoV-2 and knowledge acquired during studies on MERS and SARS would be critical assents in that perspective. For example, the indication that IFN-beta should be the most relevant interferon subtype and should be administered early as possible to optimize antiviral therapy and avoid adverse events (p. 2. 2nd col.). Sallard et al. teach clinical trials have been registered for the treatment of COVID-19 with lopinavir/ritonavir with ribavirin and IFN-beta1b. Sallard et al. teach that vapor inhalation currently performed in China offers the advantage of targeting specifically the respiratory tract, however the pharmacokinetics of the mode of administration have not been addressed (p. 2, 2nd col.). Sallard et al. teach that IFN-beta may account for a safe and easy upscale treatment against COVID-19 in the early stages of infection (p. 2, last para.).
Sallard et al. does not teach inhibiting COVID-19 infection in a subject at risk of being exposed to COVID-19 or a variant of COVID-19.
A Clinical Trial NTC04276688 (last updated 4/15/2020, previously cited) teaches a combination of Lopinavir/ritonavir, ribavirin and interferon-beta 1B for treatment of COVID-19. The Clinical Trial does not teach inhibiting COVID-19 infection in a subject at risk of being exposed to COVID-19 or a variant of COVID-19.
There was no art found that teaches or suggests interferon-beta for inhibiting COVID-19 in a subject at risk of COVID-19 or variant of COVID-19.
It is noted that pharmaceutical and biological art is generally unpredictable, requiring each embodiment to be individually assessed for physiological activity. Given this fact, historically the development of new drugs has been difficult and time-consuming. Adding to the unpredictability is that many treatment options may show promise in animal models, but may fail to show therapeutic improvement in clinical trials. There is no absolute predictability, even in view of the high level of skill in the art.
Thus, it would be highly unpredictable given that interferon-beta would be able to inhibit COVID-19 infection in a subject at risk of being exposed to COVID-19 or a variant of COVID-19.
(4) The relative skill of those in the art
MPEP 2141.03 states (in part)” A person of ordinary skill in the art is also a person of ordinary creativity, not an automaton.” KSR International Co. v. Teleflex Inc., 127 S.Ct. 1727, 167 LEd2d 705, 82 USPQ2d 1385, 1397 (2007). “[I]n many cases a person of ordinary skill will be able to fit the teachings of multiple patents together like pieces of a puzzle.” Id. Office personnel may also take into account “the inferences and creative steps that a person of ordinary skill in the art would employ.” Id. At 1396, 82 USPQ2d at 1396. The “hypothetical person having ordinary skill in the art’ to which the claimed subject matter pertains would, of necessity have the capability of understanding the scientific and engineering principles applicable to the pertinent art.” Ex parte Hiyamizu, 10 USPQ2d 1393, 1394 (Bd. Pat. App. & Inter. 1988) (disagreeing with the examiner’s definition of one of ordinary skill in the art (i.e. a doctorate level engineer or scientist working at least 40 hours per week in semiconductor research or development), and finding that the hypothetical person is not definable by way of credentials, and that the evidence in the application did not support the conclusion that such a person would require a doctorate or equivalent knowledge in science or engineering). In the instant case, the skill in the art high with respect to physicians and scientists. The level of skill in the art (physicians and scientists) would be high.
(6) The amount of direction or guidance presented (by the inventor) and (7) The presence or absence of working examples
The applicant did not provide any guidance or direction regarding inhibition of COVID-19 infection in a subject at risk of being exposed to COVID-19 or a variant of COVID-19. The instant specification does not provide any examples of in vivo or in vitro experiments disclosing the potential for interferon-beta to inhibit COVID-19 in a subject at risk. The specification has no working examples and no data to show “administering interferon-beta to at least a portion of the upper respiratory tract ” would be effective to inhibit COVID-19 infection.
(8) The quantity of experimentation necessary (to make and/or use the invention)
Owing to the factors listed above, especially in points 6 and 7, the amount of experimentation needed will be extensive in view of the lack of guidance by the inventor. MPEP 2164.01(a) states, “A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557,1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).” That conclusion is clearly justified here.
In conclusion, the instant application is not enabled for inhibiting coronavirus infection caused by COVID-19.
Response to Arguments
Applicant's arguments filed 7/24/25 have been fully considered but they are not persuasive. Applicants argue that the claims are enabled. Applicants argue that the claims are not genus claims, IFN-beta is a single compound, it is commercially available, aerosolized interferons are well studied, the claims do not specify any particular degree of relief and the level of skill in the art is high. Applicants argue that IFN-beta is not a new drug, but is a natural compound made in the body and is known to direct the immune system’s attack on viruses. Applicants argue that the Examiner acknowledges that IFN-betas activity against COVID-19 in the context of treatment (Sallard et al.). Applicants argue that the claims are not genus claims and is in contrast to the claims In re Wands, which are drawn to a genus of IgM antibodies. Applicants argue that claim 1 in Wands specified a particular high affinity, the question raised was whether it was enabled for the full scope of the claims. Applicants argue this question is not relevant to the present claims since instant claim 1 does not involve a class of compounds.
This argument was considered but is not persuasive because endogenous proteins, including IFNs are produced locally and transiently as part of a highly regulated immune cascade. Therefore, although IFN-beta is endogenous does not establish predictability or enablement of the claimed prophylactic method when administered by a different route, setting, purpose, in an uninfected human and against a novel virus. Furthermore, the Wands factors do not apply only to genus claims. A single compound can lack enablement when the claimed use is unpredictable and requires undue experimentation. The fact that the prior art suggests IFN-beta may be useful in treating established covid infection, does not infer that aerosol IFN-beta is enabled for preventing infection with COVID-19. Treatment and prophylaxis represent mechanistically distinct biological contexts. The specification and art do not disclose the dose, timing and frequency to establish antiviral state in the airway prior to exposure/infection of COVID-19.
Applicants argue that the antibodies in the Wands case needed to be generated (the legal question was whether they could make without undue experimentation). Applicants argue this question has no bearing on the present case since IFN-beta does not need to be generated. Therefore, the specification does not need examples where IFN-beta is made or formulated. Applicants argue that the specification teaches preferred doses and PHOSITA would understand the amount of drug.
This argument was considered but is not persuasive because the fact that IFN-beta is commercially available does not solve the enablement problem: whether the Applicants are enabled for the prophylaxis of COVID-19 using aerosol IFN-beta, not whether IFN-beta itself can be obtained. In the instant case, the question is not whether IFN-beta can be purchased, but whether the specification teaches how to use aerosol IFN-beta to prevent COVID-19 infection in uninfected subjects without undue experimentation.
Applicants argue that aerosolized interferons are well studied and aerosolizing devices are commercially available. Applicants argue that Vu et al. (provided by Applicants), that IFN-gamma has been aerosolized and administered to patients without side effects. Applicants argue that good results with aerosolized IFNs have been achieved against viruses. Applicants argue that para [0024] of the specification points to the NPL by Wdye et al. (also provided by Applicants) that reports with a small particle aerosol, underscoring the reasonableness of the claimed approach. Applicants discuss Brun et al. (2023, provided by Applicants) that reports IFN-beta shows good stability and activity when nebulized. Applicants also discuss Meng et al. (provided by Applicants) that administration to the nose by help prevent COVID-19 in medical staff. Applicants state that the IFN in Meng et al. is not IFN-beta. Applicants argue that the specification points to a variety of commercially available devices suitable for aerosolizing IFN-beta. Applicants argue that PHOSITA could use commercially available IFN-beta together with commercially available aerosolizing devices.
This argument was considered but is not persuasive because commercial availability of devices does not enable prophylaxis of COVID-19 with IFN-beta. Commercial availability of aerosol IFNs, including IFN-beta does not establish predictability or enablement of the claimed prophylactic method. The art and specification do not establish the correct effective dose of IFN-beta for prophylaxis, pre-exposure timing and effective delivery frequency. Thus, the commercial availability of nebulizers does not enable the claimed prophylactic use and one of ordinary skill in the art would require substantial experimentation to achieve the claimed outcome. With respect to the Meng reference, IFNs are not interchangeable. Ng et al. (“Alpha and beta type I interferons signaling: passage for diverse outcomes” Cell 2016 Jan 28;164(3):349-352) teach that there are 13 IFN-alphas in humans and 1 IFN-beta. Please note that this reference is used as an evidentiary reference to address Applicants arguments. Ng et al. teach that studies have suggested that these molecules are retained because their unique biological functions. Ng et al. teach that the various IFN species differing physical/chemical profiles, receptor affinities and downstream gene profiles are largely unclear (Abstract). Ng et al. teach that IFN-alpha and beta display different signaling activities likely due to unique binding affinities for each of the receptors and divergence in their respective complex lifetime (p. 5, 1st para.). Ng et al. teach the dichotomy uncovered between α and β IFN responses during various pathogenic infections suggest there are unique molecular and signaling pathways controlled by IFN-I that await discovery (p. 5, Conclusion). Therefore, the art teaches that IFN-alpha and beta are not interchangeable because they generate diverse and distinct biological outcomes. Thus, activity reported for IFN-alpha does not render prophylactic activity for aerosolized IFN-beta predictable and cannot substitute for an enabling disclosure. Furthermore, in addition to Meng et al. teaching a different type of IFN, the study used nasal drops for a specific amount of time and a specific dose and combined with thymosin in some groups. The regimen is specific with dose and timing and also uses other infection control methods (such as masks, caps and hand hygiene and thymosin in high risk group). The specific dose of IFN-alpha (2-3 drops/nostril 4 times a day for 28 days) when used in conjunction with standard protective measures and thymosin (high risk group) does not support the instantly claimed prophylaxis method.
Applicants argue that the claims do not specify any particular degree of relief and do not require a complete block of COVID infection. Applicants argue that it is enough to reduce infection even if that reduction is not 100%. Applicants argue that the skill in the art is high and the teachings in the art and specification would guide the highly skilled artisan such that extensive experimentation would not be needed.
The low bar argument is not persuasive because the specification does not teach how to achieve any reduction in infection by aerosolized IFN-beta in uninfected humans. There is no data, no dose, no timing, no aerosol parameter and no mucosal concentration information. The low bar for efficacy does not eliminate the requirement that the specification teach how to achieve the claimed effect. Without a teachings of the required dose, timing or frequency needed to achieve the claimed method, a skilled artisan would be left to conduct trial and error studies to determine if prophylaxis may occur. This is more than routine optimization and would require undue experimentation to determine if IFN-beta is able to prevent COVID-19 infection.
For the reasons presented above, the rejection is maintained.
Conclusion
No claims are allowed.
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 TARA L MARTINEZ whose telephone number is (571)270-1470. The examiner can normally be reached Mon-Fri 8:00-5:00.
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/TARA L MARTINEZ/Examiner, Art Unit 1654