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 .
DETAILED ACTION
This office action is in response to applicant’s reply filed on March 23, 2026.
Restrictions/Elections.
Applicant’s election without traverse of Group II (Claims 46-69) in the reply filed on March 23, 2026, is acknowledged.
Status of Claims
Claims 46-69 are currently pending and are the subject of this office action.
Claims 46-69 are presently under examination.
Priority
The present application is a CON of PCT/CN2021/088104 filed on 04/19/2021.
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 (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.
1) Claim(s) 46-49 and 61-69 is/are rejected under 35 U.S.C. 103 as being unpatentable over Cory (WO 2019/108551 06/06/2019) in view of Zhao et. al. (Hepatol. Int. (2010) 4:2-93, page 69 Abstract FP-128) and Guo et. al. (Journal of Clinical and Translational Hepatology (2020) 8:304-312), cited by Applicant).
For claim 46, Cory teaches a method of treating nonalcoholic steatohepatitis (NASH) fibrosis comprising the administration of a composition comprising a therapeutically effective amount of pirfenidone (see abstract, [0001] and claim 1).
Cory does not teach the administration of hydronidone. However, the prior art teaches that pirfenidone and hydronidone are structurally and biologically very similar:
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For example, Zhao teaches that hydronidone (F351) is a pirfenidone analog with very similar biological properties (see entire abstract (both are TGF-beta inhibitors and effective antifibrotics). Guo also teaches that pirfenidone and hydronidone are antihepatic fibrosis drugs and TGF-beta inhibitors (see title and Table 1, page 307).
Since Cory teaches a method of treating NASH comprising the administration of a composition comprising pirfenidone, and since Zhao and Guo teach that hydronidone is structurally, biologically and pharmaceutically equivalent to pirfenidone, before the effective filing date of the claimed invention it would have been prima facie obvious for a person of ordinary skill in the art to substitute one functional equivalence (pirfenidone) for another (hydronidone) with an expectation of success, since the prior art establishes that both function in similar manner, thus resulting in the practice of claim 46, with a reasonable expectation of success.
For claims 47-49, Cory further teaches that the pharmaceutical compositions can comprise 20% to 40% pirfenidone (see [0080]), which anticipates the range of claim 47, and 30% (which anticipates the range of claims 48-49). Cory also teaches that the compositions comprise pharmaceutically acceptable excipients (see [0080] on page 24).
All this will result in the practice of claims 47-49 with a reasonable expectation of success.
The statement in claim 61: “the method reduces total NASH score in the subject” does not require additional steps to be performed and simply expresses the intended result of carrying the process made obvious by the prior art: “a method for treating NASH comprising the administration of a composition comprising hydronidone".
MPEP 2111.04 states: “Claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed, or by claim language that does not limit a claim to a particular structure. However, examples of claim language, although not exhaustive, that may raise a question as to the limiting effect of the language in a claim are:
(A) “ adapted to ” or “adapted for ” clauses;
(B) “ wherein ” clauses; and
(C) “ whereby ” clauses.
The determination of whether each of these clauses is a limitation in a claim depends on the specific facts of the case. In Hoffer v. Microsoft Corp., 405 F.3d 1326, 1329, 74 USPQ2d 1481, 1483 (Fed. Cir. 2005), the court held that when a “whereby’ clause states a condition that is material to patentability; it cannot be ignored in order to change the substance of the invention.” Id. However, the court noted (quoting Minton v. Nat ’l Ass ’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)) that a “whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.” (Emphasis added).
In the instant case “reducing total NASH score in the subject” appears to be the result of the process made obvious by the prior art: “a method for treating NASH comprising the administration of a composition comprising hydronidone ", e. g. the intended result of a process step positively recited. As such, this limitation in the instantly claimed method has not been given any weight.
All this will result in the practice of claim 61 with a reasonable expectation of success.
The statement in claim 62: “the method reduces cellular ballooning in the subject” does not require additional steps to be performed and simply expresses the intended result of carrying the process made obvious by the prior art: “a method for treating NASH comprising the administration of a composition comprising hydronidone".
MPEP 2111.04 states: “Claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed, or by claim language that does not limit a claim to a particular structure. However, examples of claim language, although not exhaustive, that may raise a question as to the limiting effect of the language in a claim are:
(A) “ adapted to ” or “adapted for ” clauses;
(B) “ wherein ” clauses; and
(C) “ whereby ” clauses.
The determination of whether each of these clauses is a limitation in a claim depends on the specific facts of the case. In Hoffer v. Microsoft Corp., 405 F.3d 1326, 1329, 74 USPQ2d 1481, 1483 (Fed. Cir. 2005), the court held that when a “whereby’ clause states a condition that is material to patentability; it cannot be ignored in order to change the substance of the invention.” Id. However, the court noted (quoting Minton v. Nat ’l Ass ’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)) that a “whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.” (Emphasis added).
In the instant case “reducing cellular ballooning in the subject” appears to be the result of the process made obvious by the prior art: “a method for treating NASH comprising the administration of a composition comprising hydronidone ", e. g. the intended result of a process step positively recited. As such, this limitation in the instantly claimed method has not been given any weight.
All this will result in the practice of claim 62 with a reasonable expectation of success.
For claim 63, Cory does not say that the patients have hepatitis B virus, as such it is safe to assume that some or most of the patients are free of hepatitis B virus, thus resulting in the practice of claim 63 with a reasonable expectation of success.
For claim 64, Cory teaches the daily administration of pirfenidone (see for example [0062]), thus resulting in the practice of claim 64 with a reasonable expectation of success.
For claims 65-66, Cory teaches the daily administration of 300 mg (see [0062]), which anticipates the instantly claimed ranges (180 mg to 360 mg daily and 270 mg to 360 mg daily), thus resulting in the practice of claims 65-66 with a reasonable expectation of success.
For claim 67, Cory teaches that the subject being treated is human (see [0046]), thus resulting in the practice of claim 67 with a reasonable expectation of success.
For claim 68, Cory teaches a method of treating nonalcoholic steatohepatitis (NASH) fibrosis comprising the administration of a composition comprising a therapeutically effective amount of pirfenidone (see abstract, [0001] and claim 1).
Cory does not teach the administration of hydronidone. However, the prior art teaches that pirfenidone and hydronidone are structurally and biologically very similar:
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For example, Zhao teaches that hydronidone (F351) is a pirfenidone analog with very similar biological properties (see entire abstract (both are TGF-beta inhibitors and effective antifibrotics). Guo also teaches that pirfenidone and hydronidone are antihepatic fibrosis drugs and TGF-beta inhibitors (see title and Table 1, page 307).
Since Cory teaches a method of treating NASH comprising the administration of a composition comprising pirfenidone, and since Zhao and Guo teach that hydronidone is structurally, biologically and pharmaceutically equivalent to pirfenidone, before the effective filing date of the claimed invention it would have been prima facie obvious for a person of ordinary skill in the art to substitute one functional equivalence (pirfenidone) for another (hydronidone) with an expectation of success, since the prior art establishes that both function in similar manner.
The prior art is silent regarding “reducing total NASH score”. However: “reducing total NASH score” will naturally flow from the teachings of (or method made obvious by) the prior art (see above rejection), since the same compound (hydronidone) is being administered to the same subjects (human subjects suffering from NASH). In other words, products of identical or similar composition cannot exert mutually exclusive properties when administered under the same or similar circumstances.
In other words, even though the prior art is silent regarding “reducing total NASH score”, by practicing the method made obvious by the prior art: “a method for treating NASH comprising the administration of a composition comprising hydronidone ", one will also be “reducing total NASH score”, even though the prior art was not aware of it.
Apparently, Applicant has discovered a new property or advantage ("reducing total NASH score”) of the method made obvious by the prior art (“a method for treating NASH comprising the administration of a composition comprising hydronidone ").
MPEP 2145 II states: “The fact that Applicant has recognized another advantage which would flow naturally from following the suggestion of the prior art, cannot be the basis for patentability when the differences would otherwise be obvious”. Ex parte Obiaya, 227 USPQ 58, 60. (FP 7.37.07, MPEP 707.07(f)).
All this will result in the practice of claim 68 with a reasonable expectation of success.
For claim 69, Cory teaches a method of treating nonalcoholic steatohepatitis (NASH) fibrosis comprising the administration of a composition comprising a therapeutically effective amount of pirfenidone (see abstract, [0001] and claim 1).
Cory does not teach the administration of hydronidone. However, the prior art teaches that pirfenidone and hydronidone are structurally and biologically very similar:
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For example, Zhao teaches that hydronidone (F351) is a pirfenidone analog with very similar biological properties (see entire abstract (both are TGF-beta inhibitors and effective antifibrotics). Guo also teaches that pirfenidone and hydronidone are antihepatic fibrosis drugs and TGF-beta inhibitors (see title and Table 1, page 307).
Since Cory teaches a method of treating NASH comprising the administration of a composition comprising pirfenidone, and since Zhao and Guo teach that hydronidone is structurally, biologically and pharmaceutically equivalent to pirfenidone, before the effective filing date of the claimed invention it would have been prima facie obvious for a person of ordinary skill in the art to substitute one functional equivalence (pirfenidone) for another (hydronidone) with an expectation of success, since the prior art establishes that both function in similar manner.
The prior art is silent regarding “reducing cellular ballooning”. However: “reducing cellular ballooning” will naturally flow from the teachings of (or method made obvious by) the prior art (see above rejection), since the same compound (hydronidone) is being administered to the same subjects (human subjects suffering from NASH). In other words, products of identical or similar composition cannot exert mutually exclusive properties when administered under the same or similar circumstances.
In other words, even though the prior art is silent regarding “reducing cellular balooning”, by practicing the method made obvious by the prior art: “a method for treating NASH comprising the administration of a composition comprising hydronidone ", one will also be “reducing cellular ballooning”, even though the prior art was not aware of it.
Apparently, Applicant has discovered a new property or advantage ("reducing cellular ballooning”) of the method made obvious by the prior art (“a method for treating NASH comprising the administration of a composition comprising hydronidone ").
MPEP 2145 II states: “The fact that Applicant has recognized another advantage which would flow naturally from following the suggestion of the prior art, cannot be the basis for patentability when the differences would otherwise be obvious”. Ex parte Obiaya, 227 USPQ 58, 60. (FP 7.37.07, MPEP 707.07(f)).
All this will result in the practice of claim 69 with a reasonable expectation of success.
2) Claim(s) 50 is/are rejected under 35 U.S.C. 103 as being unpatentable over Cory (WO 2019/108551 06/06/2019) in view of Zhao et. al. (Hepatol. Int. (2010) 4:2-93, page 69 Abstract FP-128) and Guo et. al. (Journal of Clinical and Translational Hepatology (2020) 8:304-312), cited by Applicant) as applied to claims 46-49 and 61-69 above, further in view of Funaki et. al. (US 2019/0231764).
Cory in view of Zhao and Guo teaches all the limitations of claim 50, except for the pharmaceutical excipient being magnesium stearate. However, Magnesium stearate is a very commonly used pharmaceutical excipient, and in fact, Funaki teaches pharmaceutical compositions comprising pirfenidone and magnesium stearate (see [0004]), thus resulting in the practice of claim 50 with a reasonable expectation of success.
3) Claim(s) 51-54 is/are rejected under 35 U.S.C. 103 as being unpatentable over Cory (WO 2019/108551 06/06/2019) in view of Zhao et. al. (Hepatol. Int. (2010) 4:2-93, page 69 Abstract FP-128) and Guo et. al. (Journal of Clinical and Translational Hepatology (2020) 8:304-312), cited by Applicant) as applied to claims 46-49 and 61-69 above, further in view of Bates et. al. (US 2018/0311244).
Cory in view of Zhao and Guo teaches all the limitations of claims 51-54, except for the liver stiffness values.
However, Bates teaches that subjects suffering from NASH have liver stiffness values of more than 2.88 kPa (see [016]) which overlaps with the instantly claimed ranges.
MPEP 2144.05 states: 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). Even a slight overlap in range establishes a prima facie case of obviousness. In re Peterson, 65 USPQ2d 1379, 1382 (Fed. Cir. 2003).
"A prior art reference that discloses a range encompassing a somewhat narrower claimed range is sufficient to establish a prima facie case of obviousness." In re Peterson, 315 F.3d 1325, 1330, 65 USPQ2d 1379, 1382-83 (Fed. Cir. 2003). >See also In re Harris, 409 F.3d 1339, 74 USPQ2d 1951 (Fed. Cir. 2005).
All this will result in the practice of claims 51-54 with a reasonable expectation of success.
4) Claim(s) 55-57 is/are rejected under 35 U.S.C. 103 as being unpatentable over Cory (WO 2019/108551 06/06/2019) in view of Zhao et. al. (Hepatol. Int. (2010) 4:2-93, page 69 Abstract FP-128) and Guo et. al. (Journal of Clinical and Translational Hepatology (2020) 8:304-312), cited by Applicant) as applied to claims 46-49 and 61-69 above, further in view of Goldman et. al. (US 2019/0242907).
Cory in view of Zhao and Guo teaches all the limitations of claims 55-57 except for the subjects Ishak scores.
However, Goldman teaches that subjects suffering from NASH can have a Ishak score 3-4 and 5-6 (see [0175]), which either anticipate or overlap with the instantly claimed ranges.
MPEP 2144.05 states: 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). Even a slight overlap in range establishes a prima facie case of obviousness. In re Peterson, 65 USPQ2d 1379, 1382 (Fed. Cir. 2003).
"A prior art reference that discloses a range encompassing a somewhat narrower claimed range is sufficient to establish a prima facie case of obviousness." In re Peterson, 315 F.3d 1325, 1330, 65 USPQ2d 1379, 1382-83 (Fed. Cir. 2003). >See also In re Harris, 409 F.3d 1339, 74 USPQ2d 1951 (Fed. Cir. 2005).
All this will result in the practice of claims 55-57 with a reasonable expectation of success.
5) Claim(s) 58-60 is/are rejected under 35 U.S.C. 103 as being unpatentable over Cory (WO 2019/108551 06/06/2019) in view of Zhao et. al. (Hepatol. Int. (2010) 4:2-93, page 69 Abstract FP-128) and Guo et. al. (Journal of Clinical and Translational Hepatology (2020) 8:304-312), cited by Applicant) as applied to claims 46-49 and 61-69 above, further in view of Brattain et. al. (US 2021/0022715).
Cory in view of Zhao and Guo teaches all the limitations of claims 58-60 except for the subjects METAVIR scores.
However, Brattain teaches that METAVIR scores of F1, F2 and F3 are common in subjects with liver fibrosis (see [0008]), which anticipate the requirement of the instant claims, thus resulting in the practice of claims 58-60 with a reasonable expectation of success.
Conclusion
No claims are allowed.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARCOS L SZNAIDMAN whose telephone number is (571)270-3498. The examiner can normally be reached Flexing M-F 7 AM-7 PM.
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/MARCOS L SZNAIDMAN/
Primary Examiner, Art Unit 1628
March 25, 2026.
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