DETAILED ACTION
Notice of AIA Status
The instant application, filed on or after 16 March 2013, is being examined under the first inventor to file provisions of the Leahy-Smith America Invents Act (AIA ).
If the status of the application as subject to AIA or pre-AIA is incorrect, any correction of the statutory basis (e.g., changing from AIA to pre-AIA ) for a rejection under 35 U.S.C. §§ 102 and/or 103 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.
Status of the Claims
The listing of claims filed 17 May 2023 has been examined. New claims 8–14 are pending. Claims 1–7 are canceled.
Priority
The instant application was filed 17 May 2023; is a national stage application of PCT/KR2021/001312, filed 1 February 2021, and claims priority to KR 10-2020-0154110, filed 17 November 2020. Acknowledgment is made of applicant’s claim for foreign priority and a copy of the priority document has been received.
Information Disclosure Statement
The information disclosure statement (IDS) submitted 17 May 2023 is acknowledged and has been considered.
Claim Rejections - 35 U.S.C. § 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.
Claims 13 and 14 are rejected under 35 U.S.C. § 112(a) because the specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with the claims.
MPEP § 2164.01(a) explains how enablement for the claimed invention can be analyzed:
In order to determine compliance with the enablement requirement of 35 U.S.C. 112(a), the Federal Circuit developed a framework of factors in In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), referred to as the Wands factors to assess whether any necessary experimentation required by the specification is “reasonable” or is “undue.” . . . These factors include, but are not limited to:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
The Wands factors are analyzed with respect to the claimed invention in turn below.
The breadth of the claim is broad in scope. The claimed methods encompass preventing coronavirus disease, common cold, acute upper respiratory tract infection, severe acute respiratory syndrome, and viral pneumonia with rhein and/or meclofenamic acid.
The nature of the invention is sophisticated, as it relates to the pharmaceutical art and more specifically to a method of treating or preventing diseases in a subject.
The state of the prior art is in its infancy for preventing coronavirus disease, common cold, acute upper respiratory tract infection, severe acute respiratory syndrome, and viral pneumonia. In order to prevent a disease, one of skill in the art would need to identify the subjects likely to acquire such as disease, carry out the claimed invention (e.g., administer the claimed compound/composition), and demonstrate the subject did not have any cells infected by the pathogen and/or demonstrate the subject did not develop the disease as a result of the administration of the compound/composition. Examiner is aware that vaccines exist for certain viral infections, but Examiner is not aware of evidence in the instant specification or prior art that supports a claim for preventing such diseases with rhein and/or meclofenamic acid.
The level of one of ordinary skill may be found by inquiring into: (i) the type of problems encountered in the art; (ii) prior art solutions to those problems; (iii) the rapidity with which innovations are made; (iv) the sophistication of the technology; and (v) the education level of active workers in the field. Custom Accessories, Inc. v. Jeffrey-Allan Industries, Inc., 807 F.2d 855, 962 (Fed. Cir. 1986). All of the factors may not be present in every case, and one or more of them may predominate. Envtl. Designs, Ltd. v. Union Oil Co., 713 F.2d 693, 696 (Fed. Cir. 1983). Based on the typically high education level of workers in the pharmaceutical art and the high degree of sophistication required to solve problems encountered in the art, Examiner finds a person having ordinary skill in the art would have at least a college degree in chemistry, biology, biochemistry, pharmacology, or a related field, and several years of experience.
The level of predictability in the art is generally unpredictable. The relevant art requires each potential drug candidate to be assessed for physiological activity. In re Fisher, 427 F.2d 833, 166 USPQ 18, 24 (CCPA 1970). The more unpredictable an area is the more specific disclosure is necessary to satisfy the statutory requirement. MPEP § 2164.02(II) explains that a correlation between the claimed invention and the evidence provided in an application, along with a correlation between the evidence and the models recognized in the art, are required:
“Correlation” as used herein refers to the relationship between in vitro or in vivo animal model assays and a disclosed or a claimed method of use. An in vitro or in vivo animal model example in the specification, in effect, constitutes a “working example” if that example “correlates” with a disclosed or claimed method invention. If there is no correlation, then the examples do not constitute “working examples.” In this regard, the issue of “correlation” is also dependent on the state of the prior art. In other words, if the art is such that a particular model is recognized as correlating to a specific condition, then it should be accepted as correlating unless the examiner has evidence that the model does not correlate. Even with such evidence, the examiner must weigh the evidence for and against correlation and decide whether one skilled in the art would accept the model as reasonably correlating to the condition. In re Brana, 51 F.3d 1560, 1566, 34 USPQ2d 1436, 1441 (Fed. Cir. 1995) (reversing a USPTO decision based on finding that in vitro data did not support in vivo applications).
Further, treatments may be effective for some subjects and ineffective for other subjects. Thus, each candidate for pharmaceutical medicine must be evaluated on its own even when a nexus to an existing drug or class of drugs has been established.
The amount of direction provided by the inventor is limited to in vitro assays to determine which compounds can bind to galactocerebrosidase enzyme. (Spec., pp.124–128). There is no guidance with respect to methods of preventing a disease. For example, there is no guidance related to identifying subjects likely to acquire a disease, administering the claimed compound/composition, and demonstrating the subject did not have any cells infected by a pathogen or demonstrating the subject did not develop the disease as a result of administering the compound/composition.
The existence of working examples is limited to in vitro testing of rhein and meclofenamic acid, which show viral RNA inhibitory effect in those experiments. (Spec., ¶¶58–115). There are no examples demonstrating the compounds can prevent an infection or disease.
The quantity of experimentation needed to make or use the invention based on the content of the disclosure is extensive, as it includes in vitro and in vivo evaluations for each specific disease or disorder encompassed by the claims for each compound. The experimentation required to show efficacy and safety of the methods is extensive.
Scope of Enablement Conclusion
In view of the Wands factors discussed above, the disclosure of the instant application does not reasonably enable a person having ordinary skill in the art to use the full scope of the claimed invention. The breadth of the claims is broad in scope; the nature of the invention is sophisticated; the state of the prior art is in its infancy for preventing the claimed diseases; the level of skill in the art is high; the pharmaceutical art is unpredictable; the direction provided by the inventor is limited to in vitro assays of rhein and meclofenamic acid; there are no working examples for identifying subjects likely to acquire a disease, administering the claimed compound/composition, and demonstrating the subject did not develop the disease; and, finally, the quantify of experimentation needed to practice the claimed invention is extensive. Thus, when the evidence is considered as a whole, undue experimentation would be required to practice the full scope of the claimed invention.
Examiner recommends amending the claims to the treatment of subjects having the specific diseases.
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 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 12 is 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 12 depends from claim 8 and recites “the antiviral composition.” Claim 8 does not recite “an antiviral composition.” There is insufficient antecedent basis for using definite article “the” because there is no preceding recitation of indefinite article “a” or “an” in the claim it depends on. Accordingly, claim 12 lacks antecedent basis for the term.
Appropriate correction is required.
Claim Rejections - 35 U.S.C. § 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.
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.
Graham v. John Deere Co., 383 U.S. 1, 17 (1966); MPEP § 2141(II).
Claims 8–14 are rejected under 35 U.S.C. § 103 as being unpatentable over Chandel et al., Chem. Biol. Lett. 2020, 7(3), 166–175 (“Chandel”) [IDS].
The Graham factors are addressed in turn below.
Determining the scope and contents of the prior art
Chandel discloses repurposing rhein for the treatment of coronavirus (COVID-19). Chandel screened 100 FDA approved compounds and 1000 active phytochemicals from plants and selected 19 compounds for further study based on their binding affinity with COVID-19 major protease (6LU7). (Chandel, p,171). Of the selected compounds, rhein was one of the best at binding the target site of the protein. (Id.).
Chandel explains that coronaviruses have high recombination rates due to the ability to develop constant transcription errors and RNA Dependent RNA Polymerase (RdRP) jumps. (Id., p.167). Chandel states: “Most of the RNA content of these viruses encode viral polymerase, RNA synthesis materials, and two large nonstructural polyproteins . . . The rest one third of the genome portion codes for four structural proteins (spike (S), envelope (E), membrane (M) nucleocapsid (N), and the helper proteins.” (Id.). Chandel explains the coronaviruses are “associated with severe acute respiratory syndrome (SARS).” (Id.).
Ascertaining the differences between the prior art and the claims at issue
Chandel does not disclose administering rhein to a subject in need thereof.
Chandel does not disclose inhibiting the non-structural proteins listed in claim 11.
Chandel does not disclose a composition comprising a drug and, e.g., a carrier.
Resolving the level of ordinary skill in the pertinent art
The level of one of ordinary skill may be found by inquiring into: (i) the type of problems encountered in the art; (ii) prior art solutions to those problems; (iii) the rapidity with which innovations are made; (iv) the sophistication of the technology; and (v) the education level of active workers in the field. Custom Accessories, Inc. v. Jeffrey-Allan Industries, Inc., 807 F.2d 855, 962 (Fed. Cir. 1986). All of the factors may not be present in every case, and one or more of them may predominate. Envtl. Designs, Ltd. v. Union Oil Co., 713 F.2d 693, 696 (Fed. Cir. 1983). Based on the typically high education level of workers in the pharmaceutical art and the high degree of sophistication required to solve problems encountered in the art, Examiner finds a person having ordinary skill in the art would have at least a college degree in chemistry, biology, biochemistry, pharmacology, or a related field, and several years of experience.
Considering objective evidence present in the application indicating obviousness or nonobviousness
The instant application includes in vitro testing of rhein and shows viral RNA inhibitory effect in those experiments. (Spec., ¶¶58–115).
The question of obviousness
Based on the above factors, it would have been obvious for a person having ordinary skill in the art prior to the filing of the instant application to arrive at the claimed methods based on Chandel, which discloses repurposing rhein for the treatment of coronavirus (COVID-19). Although Chandel does not disclose administering rhein to a subject or formulating the drug in a composition with, e.g., a carrier, those features are implied because rhein is an FDA-approved drug. And while Chandel does not disclose the inhibition of specific proteins recited in claims 10 and 11, it does discuss the target proteins generally.
One of ordinary skill in the art would have been motivated to modify Chandel to arrive at the claimed method because it suggests treating COVID-19 with rhein. There would have been a reasonable expectation of success at arriving at the claimed method because Chandel shows rhein was one of the best drugs at binding the target site and the high level of ordinary skill in the art would be capable of administering the drug to a subject in need thereof.
The evidences in the instant specification has been considered but the results are not unexpected in view of the disclosure of Chandel, which suggests the use of rhein to treat coronavirus.
Advisory regarding joint inventors
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.
Conclusion
No claims are allowed.
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/JASON M. NOLAN/Patent Examiner, Art Unit 1623
/ADAM C MILLIGAN/Supervisory Patent Examiner, Art Unit 1623