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
The preliminary amendment filed 04/18/2025, amended claims 2, 5, 9, 12, 15, 18, 21, 23, 26, 30, 33, 35, and 37-38 and cancelled claims 3-4, 6-7, 10-11, 13-14, 16, 19-20, 22, 24-25, 27-29, 31-32, 34 and 39-48.
Claims 1-2, 5, 8-9, 12, 15, 17-18, 21, 23, 26, 30, 33 and 35-38 are pending and examined on the merits herein.
Priority
This application claims the following priority:
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Information Disclosure Statement
The instant information disclosure statement is 30 pages long and cites over 300 references. The applicant has an obligation to call the most pertinent prior art to the attention of the U.S. Patent and Trademark Office in a proper fashion. Burying one reference in one hundred other IDS references is like citing nothing. PENN YAN BOATS, INC. v. SEA LARK BOATS, INC., et. al. 175 USPQ 260 (S.D. Fla. 1972). Golden Valley Microwave Foods, Inc. v. Weaver Popcorn Co. Inc., 24 USPQ2d 1801 (U.S. District Court Northern District of Indiana, July 22, 1992), Molins PLC v. Textron, Inc., 48 F.3d 1172, 1184, 33 USPQ2d 1823 (Fed. Cir. 1995).
The examiner respectfully requests that Applicant identify the most pertinent prior art in the IDS.
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, 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 1-2, 5, 8-9, 12, 15, 17-18, and 21 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2018/028517 to Coates (published 2018, IDS of 04/23/2025) in view of Nair (A simple practice guide for dose conversion between animals and human, published 2016, PTO-892).
Coates teaches a method of treating non-alcoholic steatohepatitis (NASH) by administering to a patient an effective amount of a composition comprising
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(pgs. 25-26, claims 8, 14).
Coates exemplifies its compounds as administered daily at dosage amounts of 0.06, 2, 6, and 20mg/kg (pg. 21, lines 6-23).
Coates teaches oral administration as the preferred mode of administration (pg. 6, line 29-pg. 7, line 2).
Regarding claim 1, while Coates teaches a method of treating NASH by orally administering a therapeutically effective amount of
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daily, it differs in that it does not teach a dose of from about 0.5mg to about 25 mg.
Nair teaches extrapolation of doses between species. Nair teaches that to convert a mouse dose in mg/kg to a human dose, multiply the animal dose by 0.081 (pg. 29, Table 1; abstract).
Nair teaches the average human body weight as 60 kg (g. 28, Col. 2).
Thus, in a 60kg human, a 0.06, 2, 6 and 20mg/kg mouse dose is a 0.29mg, 9.72mg, 29mg, and 97mg dose in a human. For example 0.06mg/kg (mouse dose) x 0.081 = 0.00486 mg/kg (human dose). 0.00486mg/kg (human dose) x 60kg (average weight of human body) = 0.29mg.
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to modify the mouse dosage amounts taught by Coates to human dosage amounts, to arrive at instant claim 1. One of ordinary skill in the art would have been motivated to make such a modification, with a reasonable expectation of success, because Nair teaches the instantly exemplified mouse dosages as equivalent to ~0.29mg-97mg dosages in an adult human of average weight, and in the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists (MPEP 2144.05).
Thus, an ordinary skilled artisan would have been motivated to make such a modification to predictably arrive at the most therapeutically effective method of treating NASH in an individual, human patient (see also pg. 6, lines 11-21 of Coates).
Regarding claims 2 and 5, Coates additionally teaches:
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(pg. 6, lines 11-21).
As stated in MPEP 2144.05(II), "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation."
The optimization of known amounts for known active agents is considered well within the competence level of an artisan of ordinary skill in the pharmaceutical sciences; it has been held that the selection of optimal parameters, such as amounts of active agents, to achieve a beneficial effect, is within the skill in the art of an ordinary artisan. See In re Boesch, 205 USPT 215 (CCPA 1980).
Thus, modifying dosage amounts is within the ordinary skill level of an artisan in the pharmaceutical arts.
Regarding instant claims 8-9, 12, 15, and 17-18, while the combination of Coates and Nair does not explicitly teach methylamine concentrations or steady state AUC, the method of treating NASH by orally administering a therapeutically effective amount of
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, would be expected to have the same properties, since it is administered for the same purpose (treating NASH) in an effective amount to treat NASH (the instant specification teaches a therapeutically effective amount as a dose of a compound or composition that results in reduction or inhibition of symptoms or a prolongation of survival in a patient), to the same patient population (patients with NASH), as instantly claimed. Thus, while the prior art does not explicitly teach these properties, burden is on Applicant to show that the prior art does not have these properties.
Applicants are reminded that the office does not have the facilities and resources to provide the factual evidence needed in order to establish that the product of the prior art does not possess the same material, structural and functional characteristics of the claimed product. In the absence of evidence to the contrary, the burden is on the applicant to prove that the claimed product is different from those taught by the prior art and to establish patentable differences. See In re Best 562F.2d 1252, 195 USPQ 430 (CCPA 1977) and Ex parte Gray 10 USPQ 2d 1922 (PTO Bd. Pat. App. & Int. 1989).
Regarding claim 21, Coates teaches oral administration as discussed in the above 103 rejection.
Claims 23, 26, 30, and 33 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2018/028517 to Coates (published 2018, IDS of 04/23/2025) in view of Nair (A simple practice guide for dose conversion between animals and human, published 2016, PTO-892), as applied to claims 1-2, 5, 8-9, 12, 15, 17-18, and 21, above, and further in view of Collett (Dosage regimens, published 2015, IDS of 04/23/2025).
Coates and Nair are applied as discussed in the above 35 USC 103 rejection and incorporated herein.
Regarding claim 23, while the combination of Coates and Nair teaches a method of treating NASH by orally administering an effective amount of about of
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, it differs in that it does not teach every other day administration, twice weekly administration, or once weekly administration.
Collet teaches dosage regimens (see whole document).
The design of a dosage regimen determines the therapeutic benefit for patients. The principles of clinical pharmacokinetics are applied to design a dosage regimen for a patient that ensures the appropriate formulation of drug is chosen for an appropriate route of administration. On the basis of the patient’s drug handling parameters, which require an understanding of absorption, distribution, metabolism and excretion, the dosage regiment for the medicine in a particular patient, can be optimized. The pharmacist needs to ensure the appropriate regimen is prescribed to achieve optimal efficacy and minimal toxicity (Collet--pg. 2, paragraph 1).
Pharmacokinetics enables absorption, distribution, metabolism, and excretion (ADME) to be quantified (Collet--pg. 2, paragraph 2).
Physiological factors, physicochemical properties of a drug and dosage form are factors that are considered in determining a therapeutically effective concentration of a drug in the plasma following oral administration of a single dose of drug (Collet--pg. 3, 2nd paragraph).
Whilst a single dose of certain drugs may be used in some clinical situations, most medicines are given as a multiple dosage regimen. The design of the regimen, i.e. formulation, route of administration, dose size and the dosage frequency are important factors which influence what plasma concentration is achieved and maintained in the body over the prescribed course of drug treatment. Other factors to consider are: patient choice and lifestyle, including the route of administration, the dosing interval needs to be suitable for a patient’s work pattern and the dosage form must be appropriate. (Collett-pg. 3, 3rd paragraph).
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to modify the dosage regimen of the combination of Coates and Nair to arrive at instant claim 23. One of ordinary skill in the art would have been motivated to make such a modification, with a reasonable expectation of success, because:
-Collett teaches that the design of a drug regimen, i.e. formulation, route of administration, dose size and the dosage frequency, are important factors, which influence what plasma concentration is achieved and maintained in the body over the prescribed course of drug treatment,
-Collett teaches that the pharmacist needs to ensure the appropriate regimen is prescribed to achieve optimal efficacy and minimal toxicity, and
-"[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." MPEP 2144.05(II).
As such, it is well within the skill level of an ordinary artisan to optimize the frequency of administration in methods such as that taught by the combination of Coates and Nair, to predictably arrive at a therapeutically effective dosage regimen to treat NASH.
Claims 26 and 30 depend from claim 23, and are directed toward mg dosage amounts. These limitations have been addressed in the previous rejection.
Regarding claim 33, Coates teaches oral administration as discussed in the above 103 rejection.
Claims 35 and 36 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2018/028517 to Coates (published 2018, IDS of 04/23/2025) in view of Nair (A simple practice guide for dose conversion between animals and human, published 2016, PTO-892), as applied to claims 1-2, 5, 8-9, 12, 15, 17-18, and 21, above, and further in view of US 2022/0135540 to Sweetana (effectively filed 10/15/2020, IDS of 04/23/2025).
Coates and Nair are applied as discussed in the above 35 USC 103 rejections.
Regarding claims 35-36, the combination of Coates and Nair differs in that it does not teach a FXR agonist.
Sweetana teaches a method of treating NASH by administering a therapeutically effective amount of
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, a potent FXR agonist (pg. 14, claims 2, 47-48, 51; paragraphs 3-4).
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to add the
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of Sweetana to the combined method of Coates and Nair, to arrive at the instant claims 35-36. One of ordinary skill in the art would have been motivated to make such an addition, with a reasonable expectation of success, because
-Coates teaches methods of treating NASH by administering
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, -Sweetana teaches methods of treating NASH by administering
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, and
-"It is prima facie obvious to combine two compositions each of which is taught by the
prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980), MPEP 2144.06.
Claims 37 and 38 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2018/028517 to Coates (published 2018, IDS of 04/23/2025) in view of Nair (A simple practice guide for dose conversion between animals and human, published 2016, PTO-892), as applied to claims 1-2, 5, 8-9, 12, 15, 17-18, and 21, above, and further in view of US 2022/0135540 to Sanyal (Pioglitazone, Vitamin E, or Placebo for Nonalcoholic Steatohepatitis, published 2010, PTO-892).
Coates and Nair are applied as discussed in the above 35 USC 103 rejections.
Regarding claims 35-36, the combination of Coates and Nair differs in that it does not teach vitamin E.
Sanyal teaches a method of treating NASH by administering Vitamin E, wherein the treatment reduces serum alanine and aspartate aminotransfersase, reduces hepatic steatosis, and reduces lobular inflammation (abstract; pg. 1683, Table 3; pg. 1684).
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to add the vitamin E of Sanyal to the combined methods of Coates and Nair, to arrive at the instant claims 37-38. One of ordinary skill in the art would have been motivated to make such an addition, with a reasonable expectation of success, because
-Coates teaches methods of treating NASH by administering
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, -Sanyal teaches methods of treating NASH by administering
Vitamin E, and
-"It is prima facie obvious to combine two compositions each of which is taught by the
prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980), MPEP 2144.06.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAUREN WELLS whose telephone number is (571)272-7316. The examiner can normally be reached M-F 7:00-4:30.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James (Jim) Alstrum-Acevedo can be reached on 571-272-5548. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/LAUREN WELLS/Primary Examiner, Art Unit 1622
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