DETAILED ACTION
This office action is in response to applicant’s filing dated September 30, 2025.
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 .
Status of Claims
Claims 1, 5-8, and 10-17 are pending in the instant application. Acknowledgement is made of Applicant's remarks and amendments filed September 30, 2025. Acknowledgement is made of Applicant's amendment of claims 1, 5, 8, 10, and 11; cancelation of claims 2-4 and 9; and addition of new claims 13-17.
Election/Restrictions
Applicant’s election of Group I, drawn to a pharmaceutical composition comprising (A) a therapeutically effective amount of the first ingredient wherein the first ingredient is a berberine analog, (B) a therapeutically effective amount of a second active ingredient, which is a JAK inhibitor in the reply filed on September 30, 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Claims 10, 11, 16, and 17 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on September 30, 2025.
Applicant’s election of berberrubine:
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as the elected compound of Formula (II), (III), or (IV) species and tofacitinib:
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as the JAK inhibitor species in the reply filed on September 30, 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)).
Claim 15 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on September 30, 2025.
Claims 1, 5-8, and 12-14 are presently under examination as they relate to the elected species: Berberrubine and Tofacitinib.
Priority
The present application is a 371 of PCT/CN2021/083421 filed on March 26, 2021, which claims benefit of foreign priority to CHINA 202010225184.7 filed on March 26, 2020.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on September 26, 2022 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner, except where marked with a strikethrough.
Drawings
Acknowledgement is made of the drawings received on April 7, 2023. These drawings are accepted.
Claim Rejections - 35 USC § 112
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.
Claims 1, 7, and 8 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a written description rejection.
The Written Description Guidelines for examination of patent applications indicates, "the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical characteristics and/or other chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show applicant was in possession of the claimed genus." (Federal register, Vol. 66, No. 4, pages 1099-1111, Friday January 5, 2001, see especially page 1106 column 3) and (see MPEP 2164).
Claims 1, 7, and 8 are directed to a pharmaceutical composition comprising (A) a therapeutically effective amount of the first ingredient wherein the first ingredient is a berberine analog, berberrubine (B) a therapeutically effective amount of a second active ingredient, which is a JAK inhibitor. Thus, the claims encompass a composition comprising berberrubine and a genus of compounds which function as a JAK inhibitor. Thus, the claims encompass a genus of compounds which function as a JAK inhibitor with no other defining structural components of the compound. JAK inhibitors can be a small molecule, polypeptide, peptide, glycoprotein, peptide-mimetic, an antigen binding protein (ABP), a DNA, an RNA, RNAi, siRNA, shRNA, a peptide nuclei acid (PNA), a genetic construct for targeting gene editing, a CRSIPR/Cas9 construct, a guide nucleic acid and tracrRNA. Thus, the claims encompass a genus of molecules which function as a JAK inhibitor with no other defined structural components to produce a composition combined with berberrubine.
In a review of the instant specification, the specification does not appear to provide guidance as to what structural components are critical to the desired function (see below). The specification discloses about 24 compounds as JAK inhibitors but only disclose the efficacy of 2 compounds in combination with berberrubine. Because there are an innumerably large number of bio-molecules/compounds within the scope of the generic claims, it would require extensive manpower to make and test each compound to determine which compound would possess the recited properties (i.e., function as a JAK inhibitor) and be useful in the instantly claimed compositions.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed by him. The courts have stated:
"To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997); In re Gostelli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) ("[T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed."). Thus, an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious," and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966." Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
Further, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents of the University of California v. Eli Lilly & Co. the court stated:
"A written description of an invention involving a chemical genus, like a description of a chemical species, 'requires a precise definition, such as by structure, formula, [or] chemical name,' of the claimed subject matter sufficient to distinguish it from other materials." Fiers, 984 F.2d at 1171, 25 USPQ2d 1601; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284985 (CCPA 1973) ("In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus …") Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The MPEP further states that if a biomolecule is described only by a functional characteristic, without any disclosed correlation between function and structure, it is "not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence." MPEP § 2163. The MPEP does state that for a generic claim the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. MPEP § 2163. If the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. See MPEP § 2163. Although the MPEP does not define what constitute a sufficient number of representative species, the courts have indicated what do not constitute a representative number of species to adequately describe a broad generic. In Gostelli, the courts determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gostelli, 872, F.2d at 1012, 10 USPQ2d at 1618.
In the instant case, the claims are drawn to a pharmaceutical composition comprising (A) a therapeutically effective amount of the first ingredient wherein the first ingredient is a berberine analog, berberrubine (B) a therapeutically effective amount of a second active ingredient, which is a JAK inhibitor. Thus, the claims encompass a genus of molecules which function as a JAK inhibitor with no other defined structural components to produce a composition combined with berberrubine.
The claims are generic, broadly reciting a genus of “a JAK inhibitor.”
As stated supra, the MPEP states that written description for a genus can be achieved by a representative number of species within a broad generic. It is unquestionable that claims 1, 7, and 8 are broad and generic, with respect to all possible compounds encompassed by the claims.
Applicant has failed to show that they were in possession of all the diverse compounds encompassed by a JAK inhibitor. Applicant discloses a very narrow set of compounds described as a JAK inhibitor, despite claiming any compound functioning as a JAK inhibitor. The possible variation of any molecule that functions as a JAK inhibitor within the scope of claims 1, 7, and 8 are limitless and would encompass compounds that function as a JAK inhibitor not yet discovered. In a review of the specification, the specification discloses about 24 compounds as JAK inhibitors but only disclose the efficacy of 2 compounds in combination with berberrubine. Because there are an innumerably large number of bio-molecules/compounds within the scope of the generic claims, it would require extensive manpower to make and test each compound to determine which compound would possess the recited properties (i.e., function as a JAK inhibitor) and be useful in the instantly claimed compositions. The small set of compounds cannot be viewed as being reasonably representative of the genus in its claimed scope because no readily apparent combination of identifying characteristics is provided.
Given the broad scope of the claimed subject matter, Applicant has not provided sufficient written description that would allow the skilled in the art to recognize all the compounds claimed to be useful in the compositions of claims 1, 7, and 8.
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.
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 1, 5, 6, 8, and 12-14 are rejected under 35 U.S.C. 103 as being unpatentable over Li et al (CN108272802 A, cited in the IDS, machine translation obtained from WIPO PatentScope January 21, 2026) in view of Yu et al (PLoS ONE, 2018; 13(3): e0194069 pp. 1-15).
Regarding claims 1, 5, 6, and 12-14, Li teaches a combined drug for relieving and treating ulcerative colitis comprising berberine and tofacitinib (claim 1). Li does not teach the composition comprises berberrubine.
However, Yu teaches berberrubine (BB) is deemed as one of the major active metabolite of berberine (BBR), a naturally-occurring isoquinoline alkaloid with appreciable anti-UC (ulcerative colitis) effect; BB exerted similar effect to its analogue BBR and positive control in attenuating DSS(dextran sodium sulfate )-induced UC with much lower dosage and similar mechanism; BB possesses pronounced anti-UC effect similar to BBR and sulfasalazine with much smaller dosage(abstract). Yu teaches the chemical structures of berberine and berberrubine (Fig. 1):
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Berberine differs from berberrubine in that berberine contains an O-CH3 in position 9, while berberrubine contains an -OH. Thus, Yu establishes that berberine and berberrubine are structurally similar compounds and both possess anti-ulcerative colitis effects.
As such, since Li teaches a combined drug for relieving and treating ulcerative colitis comprising berberine and tofacitinib, and since Yu teaches that berberine and berberrubine are structurally similar compounds and both possess anti-ulcerative colitis effects, it would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to substitute berberine with berberrubine in the composition taught by Li with an expectation of success, since the prior art establishes that berberine and berberrubine are structurally similar compounds and both possess anti-ulcerative colitis effects. One of ordinary skill in the art would have been further motivated to substitute berberine with berberrubine since the prior art teaches berberrubine exerted similar effect to its analogue berberine with much lower dosage and similar mechanism.
Regarding the ratio of instant claims 1 and 12, Li teaches the amount of berberine in the combined drug is preferably berberine in an amount of berberine (1/3-2/3) of berberine, and the dosage of tofacitinib is (2/3-1/3) of the conventional clinical dosage of tofacitinib, and in the amount of berberine (1 /3-2/3) + tofacitinib (1/3-2/3) = 1 (page 1, last paragraph); berberine was administered 40 mg/kg/d (page 2, Examples (3)) and tofacitinib was administered 30 mg/kg/d (page 2, Examples (4). An amount of 40 mg/kg/d of berberine and an amount of tofacitinib of 30 mg/kg tofacitinib would result in a ratio of first ingredient to second ingredient of about 1.3 : 1.
It would have been prima facie obvious to one of ordinary skill in the art to utilize the amounts and ratios of berberine and tofacitinib taught by Li as a starting point for optimizing the amounts and ratio of berberrubine and tofacitinib utilized to produce a combination for the treatment of ulcerative colitis, since the prior art teaches berberine and berberrubine are structurally similar compounds and both possess anti-ulcerative colitis effects and because dosage and ratio are result-effective variables, i.e. a variable that achieves a recognized result. Therefore, the determination of the optimum or workable dosages would have been well within the practice of routine experimentation by the skilled artisan. Furthermore, absent any evidence demonstrating a patentable difference between the compositions and the criticality of the claimed dosage range, the determination of the optimum or workable dosing regimen given the guidance of the prior art would have been generally prima facie obvious to the skilled artisan. Please see MPEP 2144.05 [R-2](II)(A) and In re Aller, 220 F. 2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). ("[W]here the general conditions of claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.").
Regarding claim 8, Li teaches separate treatment groups berberine was administered 40 mg/kg/d (page 2, Examples (3)) and tofacitinib was administered 30 mg/kg/d (page 2, Examples (4)) and a combined treatment group (page 2, Examples (5)). Thus, Li suggests administration of separate compositions. It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to make a kit comprising a composition comprising berberrubine and a composition comprising tofacitinib for the treatment of ulcerative colitis with a reasonable expectation of success, since the prior art establishes that separate compositions comprising berberrubine and tofacitinib are known in the art.
With regard to the limitation directed to an instruction for use, this limitation is not given patentable weight.
MPEP 2111.05 states:
To be given patentable weight, the printed matter and associated product must be in a functional relationship. A functional relationship can be found where the printed matter performs some function with respect to the product to which it is associated. See Lowry, 32 F.3d at 1584, 32 USPQ2d at 1035 (citing Gulack, 703 F.2d at 1386, 217 USPQ at 404).
Additionally, where the printed matter and product do not depend upon each other, no functional relationship exists. For example, in a kit containing a set of chemicals and a printed set of instructions for using the chemicals, the instructions are not related to that particular set of chemicals. In re Ngai, 367 F.3d at 1339, 70 USPQ2d at 1864.
Taken together, all this would result in composition of claims 1, 5, 6, 8, and 12-14 with a reasonable expectation of success.
Conclusion
Claims 1, 5, 6, 8, and 12-14 are rejected.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RAYNA B RODRIGUEZ whose telephone number is (571)272-7088. The examiner can normally be reached 8am-5:00pm, Monday - Thursday.
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/Rayna Rodriguez/ Primary Examiner, Art Unit 1628