DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Claims
Claims 1-32 have been canceled.
Claims 33-52 are currently pending.
Election/Restrictions
Applicant’s election of Group I, Claims 33-46, in the reply filed on 8/20/2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 47-52 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected inventions and species, there being no allowable generic or linking claims.
Claims 33-46 are being examined in this application.
Claim Rejections – 35 USC § 112
The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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 33-46 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of treating SARS-CoV-2 virus infection and Ebola virus infection by administering bromelain and acetylcysteine, does not reasonably provide enablement for a method of preventing SARS-CoV-2 virus infection and Ebola virus infection and any other viral infections by administering bromelain and acetylcysteine instantly claimed. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
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. These factors include, but are not limited to: (a) breadth of the claims; (b) nature of the invention; (c) state of the prior art; (d) level of one of ordinary skill in the art; (e) level of predictability in the art; (f) amount of direction provided by the inventor; (g) existence of working examples; and (h) quantity of experimentation needed to make or use the invention based on the content of the disclosure. (See Ex parte Forman 230 USPQ 546 (Bd. Pat. App. & Inter. 1986) and In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988).
The above factors, regarding the present invention, are summarized as follows:
The breadth of the claims – The breadth of the claims is drawn to a method of prophylaxis (prevention) or treating SARS-CoV-2 virus infection and Ebola virus infection by administering bromelain and acetylcysteine.
The Nature of the invention – The nature of the invention is drawn to the administration of bromelain and acetylcysteine for treating SARS-CoV-2 virus infection and Ebola virus infection.
The state of the prior art / The predictability or lack thereof in the art – The state of the prior art is that the pharmacological art involves screening in vitro and in vivo of the selected composition to determine the desired pharmacological activities (i.e. what compositions can treat which specific disease by what mechanism). There is no absolute predictability even in view of the seemingly high level of skill in the art. The existence of these obstacles establishes that the contemporary knowledge in the art would prevent one of ordinary skill in the art from accepting any therapeutic regimen on its face.
“Prevention” provides the expectation that the diseases/disorders or conditions do not occur in response to a challenge or initiating event. While there is no requirement that prevention must be absolute in all cases, there is a reasonable expectation that some element of prevention can be shown. The standard for such is extremely high, and it is expected that the showing will be actual rather than implied, prophetic, or with a model. The standard of enablement is higher for such inventions because effective preventions of disease conditions are relatively rare and may even be unbelievable in the absence of strong supporting evidence.
With respect to Applicant’s claims to prevention, there are no known compositions that have been demonstrated to prevent SARS-CoV-2 virus infection and Ebola virus infection instantly claimed.
The relative skill of those in the art – The relative skill of those in the art is high, with a typical practitioner possessing commensurate degree level, as well as several years of professional experience.
The amount of direction or guidance present – There is no direction or guidance present for the prevention of SARS-CoV-2 virus infection and Ebola virus infection and any other viral infections, by administering the instant composition.
Examples provided in the specification demonstrate treating SARS-CoV-2 virus infection and Ebola virus infection by administering bromelain and acetylcysteine, however, the disclosure does not provide how the in vivo data correlates to the prevention of the viral infection of the instant claims.
The presence or absence of working examples – The working examples present in the instant specification are directed to treating SARS-CoV-2 virus infection and Ebola virus infection using bromelain and acetylcysteine.
With respect to the prevention of the instant viral infections, there is no evidence of record, which would enable the skilled artisan in the identification of the subjects who have the potential of becoming afflicted with the viral infections claimed herein. That a single composition can be used to treat or prevent the viral infections embraced by the claims is an incredible finding for which Applicant has not provided supporting evidence. Applicant has not provided any competent evidence or disclosed tests that are highly predictive for the pharmaceutical use for treating or preventing viral infections by administering the instant claimed composition.
The quantity of experimentation needed – The quantity of experimentation needed is undue experimentation. One of skill in the art would need to determine what viral infections instantly encompassed by the claims would be benefited by administering bromelain and acetylcysteine and would furthermore then have to determine the claimed composition in the instant invention would provide treatment of the infections. Furthermore, one of ordinary skill in the art would need to determine which patients not having particular diseases would otherwise develop them and administer the instant composition over such an extended period of time as to determine true prevention. Such a task has yet to be accomplished in the art and the instant specification provides no particular guidance on how to accomplish such a task.
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)}.
Genetech, 108 F.3d at 1366, states that, “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion.” And “patent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable.”
Therefore, in view of the Wands factors discussed above, to practice the claimed invention herein, a person of skill in the art would have to engage in undue experimentation to test which diseases can be prevented or treated by the composition encompassed in the instant claims, with no assurance of success.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis 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 of this title, 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.
Claims 33-37, 40, 42-43 and 45 are rejected under 35 U.S.C. 103 as being unpatentable over Sutton et al (WO 90/02562; 3/22/1990. Cited on IDS) in view of Jones et al (US 6,013,632; 1/11/2000.).
The instant claims recite a method for the prophylaxis or treatment of a viral infection in a patient, the method comprising administering to the patient a therapeutically effective amount of a combination of a glycoprotein affecting protease and a disulphide bond breaking agent.
Sutton teaches a method of treating a viral infection in a subject comprising administering a therapeutically effective amount of a protease enzyme such as a bromelain (a glycoprotein affecting protease, a cysteine protease) (Abstract, p.5 para 3). Since the bromelain of Sutton is the same as the claimed bromelain, the bromelain of Sutton is effective to hydrolyse glycosidic bonds of glycoproteins in a virus. Said administration is in the form of a nasal spray (p.5 para 2). The protease may be used in combination with other therapeutic agents having an antiviral activity (p.5 para 4).
Sutton does not teach the method comprises a disulphide bond breaking agent (claim 33), wherein the disulphide bond breaking agent is acetylcysteine (NAC) (claim 37).
However, Sutton does teach the method is for treating and preventing infection with enveloped viruses including influenza viruses (p.1 para 2). Jones teaches a method of treating or prophylactic preventing influenza virus infection comprising administering to a patient in need of such treatment a pharmaceutical composition comprises a therapeutically effective amount of N-acetyl-L-cysteine (Abstract, col.3 line 47-49 & 53, col.9 line 9-10). Delivery of the composition is carried out in the form of nasal spray (col.2 line 65).
Thus, before the effective filing date of the claimed invention, it would have been obvious to one of ordinary skill in the art to combine bromelain and N-acetyl-L-cysteine in a method of treating or preventing influenza virus infection, as disclosed by Sutton and Jones above, since each was well known in the art for the same purpose. Moreover, before the effective filing date of the claimed invention, one of ordinary skill in the art would have been motivated by the cited reference to combine bromelain and N-acetyl-L-cysteine with a reasonable expectation for successfully treating or preventing influenza virus infection.
Claims 38-39, 41 and 44 are rejected under 35 U.S.C. 103 as being unpatentable over Sutton et al (WO 90/02562; 3/22/1990. Cited on IDS) in view of Jones et al (US 6,013,632; 1/11/2000.) as applied to claims 33-37, 40, 42-43 and 45 above, further in view of Zhao et al (Ann Transl Med. 2019;7(18):487.).
References cited above do not teach the method wherein the combination is administered into the lungs of the patient (claim 38), the combination is nebulized before administration (claim 39), the combination is administered to the patient immediately upon the patient becoming symptomatic (claim 41), and the protease, disulphide bond breaking agent, and any other additional therapeutic agent are administered to the patient simultaneously, separately or sequentially (claim 44).
However, Sutton and Jones both teach the method of treating or preventing influenza virus infection (a respiratory disease), and Sutton does teach the method wherein the protease may be used in combination therapies together with other therapeutic agents having an antiviral activity, and combination therapies involving simultaneous or successive administration (p.5 para 4). Zhao teaches nebulization therapy has a unique and vital position in the treatment of respiratory diseases, it has several advantages, such as the rapid onset of action, proved efficacy, good safety profile, and is widely used in many respiratory diseases (p.1 col left – para 2). Nebulization therapy aims to deliver a therapeutic dosage of a drug through the mouth, nose or artificial airway into airways and lungs (p.1 col right – para 2). If symptoms or signs of airway hyperreactivity is indicated, the nebulization treatment is recommended (p.8 col right – para 5).
Thus, before the effective filing date of the claimed invention, it would have been obvious to one of ordinary skill in the art to nebulize the combination before administer the combination into the lungs of a patient, to administer the combination to the patient immediately upon the patient becoming symptomatic, and to administer a protease, a disulphide bond breaking agent, and any other additional therapeutic agent to the patient simultaneously, separately or sequentially, since Sutton and Jones both disclose a method of treating or preventing influenza virus infection (a respiratory disease), Sutton discloses that a protease in combination with other therapeutic agents having an antiviral activity may be administered simultaneously or successively, and Zhao discloses that nebulization therapy provides several advantages, such as the rapid onset of action, proved efficacy, good safety profile, and is widely used in many respiratory diseases, and that if symptoms or signs of airway hyperreactivity is indicated, the nebulization treatment is recommended. Moreover, before the effective filing date of the claimed invention, one of ordinary skill in the art would have been motivated by the cited references to nebulize the combination before administer the combination into the lungs of a patient, to administer the combination to the patient immediately upon the patient becoming symptomatic, and to administer a protease, a disulphide bond breaking agent, and any other additional therapeutic agent to the patient simultaneously, separately or sequentially, with a reasonable expectation for successfully treating or preventing influenza virus infection.
Claim 46 is rejected under 35 U.S.C. 103 as being unpatentable over Sutton et al (WO 90/02562; 3/22/1990. Cited on IDS) in view of Jones et al (US 6,013,632; 1/11/2000.) as applied to claims 33-37, 40, 42-43 and 45 above, further in view of Cao (Nature Reviews Immunology. 2020;20:269-270.) and Lotz-Winter (Planta Med. 1990;56:249-253.).
References cited above do not teach the viral infection is COVID-19 or Ebola virus disease (claim 46).
However, before the effective filing date of the claimed invention, it was well-known in the art that inflammatory responses play a critical role in the progression of COVID-19 (p.270 col left – para 2, for example), as evidenced by Cao. In addition, Cao teaches the combined use of anti-inflammatory and antiviral drugs may be more effective than using either modality alone (p.270 col right – para 2). Sutton does teach a method of treating a viral infection in a subject comprising administering a protease enzyme such as a bromelain (Abstract, p.5 para 3), wherein the protease may be used in combination with other therapeutic agents having an antiviral activity (p.5 para 4). In addition, Lotz-Winter teaches that bromelain has anti-inflammatory effect (Abstract).
Thus, before the effective filing date of the claimed invention, it would have been obvious to one of ordinary skill in the art to treat viral infection including COVID-19, since Sutton and Jones both disclose a method of treating or preventing a viral infection, Sutton discloses that the method comprises administering a protease such as bromelain in combination with other therapeutic agents having an antiviral activity, Lotz-Winter discloses that bromelain has anti-inflammatory effect, and Cao discloses that the combined use of anti-inflammatory and antiviral drugs may be more effective than using either modality alone for treating COVID-19. In other words, before the effective filing date of the claimed invention, a skill in the art would use anti-inflammatory agents such as bromelain in combination with other antiviral agents to treat inflammation from COVID-19. Moreover, before the effective filing date of the claimed invention, one of ordinary skill in the art would have been motivated by the cited references to treat viral infection including COVID-19 with a reasonable expectation of success.
Conclusion
No claims are allowed.
Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LYNN Y FAN whose telephone number is (571)270-3541. The examiner can normally be reached on M-F 7am-4pm.
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/Lynn Y Fan/
Primary Examiner, Art Unit 1759