DETAILED ACTION
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 the Claims
The status of the claims are as follows:
Claims 1-7 are pending.
Claims 1-7 are rejected.
Priority
Acknowledgement is made that Instant Application 18/906,683, filed on 2024, Oct. 04, is a Continuation of PCT/KR2023/004665, filed on 2023, Apr. 06, which claims foreign priority to KR 10-2022-0042665, filed on 2022, Apr. 06. It is noted, however, that applicant has not filed a certified, translated copy of the foreign application as required by 37 CFR 1.55. Accordingly, the claims of the Instant Application will receive the priority date to the application PCT/KR2023/004665, filed on 2023, Apr. 06.
Information Disclosure Statement
The information disclosure statement(s) (IDS) submitted on 2024, Oct. 04 is/are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement(s) is/are being considered by the examiner.
Claim Objections
Claim 7 is objected to for the following reason:
The claim recites the limitation “the method according to claim 1, further comprising one or more pharmaceutically acceptable carriers.” It is unclear whether the limitation is referring to 1. the method of claim further comprising administrating one or more pharmaceutically acceptable carriers or 2. a pharmaceutical composition of claim 1, further comprising one or more pharmaceutically acceptable carriers. For the purposes of this examination, the claim will be taken to mean option 2.
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 3 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. Specifically, the claim recites the limitation “the pharmaceutical composition for the prevention or treatment of pulmonary fibrosis according to claim 1”, however, there is insufficient antecedent basis for this limitation in the claim. For the purposes of this examination, it will be interpreted to be “a pharmaceutical composition.”
Claim 3 is directed to a both product claim (“[a] pharmaceutical composition … wherein the pharmaceutically acceptable salt is a sodium salt”) and a method of use claim (“for the prevention or treatment of pulmonary fibrosis”), rendering the limitation ambiguous. The claim must be amended to limit the scope to either a composition or a method of use.
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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.
Claim(s) 1-7 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tong (Tauroursodeoxycholic Acid Alleviates Pulmonary Endoplasmic Reticulum Stress and Epithelial-Mesenchymal Transition in Bleomycin-Induced Lung Fibrosis. BMC Pulmonary Medicine, 2021, 21:149. doi.org/10.1186/s12890-021-01514-6) in view of NCBI Clinical Trial ID NCT04727320 (The Clinical Application of Tauroursodeoxycholic Acid in Patients with Liver Fibrosis. First posted 2021, Jan., 27), and in view of Seong (WO 2022/059946, published 2022, Mar. 24; priority claim to Provisional Application 63/080,112, dated 2020, Sept. 18).
Claims 1-2 are directed to a method for the prevention or treatment of pulmonary fibrosis, comprising the step of administering taurodeoxycholic acid (TDCA) or a pharmaceutically acceptable salt there to an individual, wherein the TDCA is a compound represented by Formula I, below (Table 1, top).
Tong teaches idiopathic pulmonary fibrosis (IPF) is characterized by excessive deposition of collagen, and bleomycin (BLM) causes dose-dependent interstitial lung fibrosis (page 1, left column, paragraph 1). BLM-evoked lung fibrosis has been used extensively in animal experiments for its resemblance to human interstitial pulmonary fibrosis (page 1, right column, paragraph 1). Tong further teaches a method of treating said BLM-evoked lung fibrosis with tauroursodeoxycholic acid (TUDCA, Table 1, bottom) comprised of administering to the individual a pharmaceutical composition of TUDCA. The method is comprised of dividing 80 mice into four groups at random, wherein: one group received intraperitoneal injections of TUDCA (250 mg/kg) once a day for 21 days; one group received a single intratracheal injection of BLM (3.0 mg/kg); one group received TUDCA + BLM (intraperitoneal injections of TUDA at 250 mg/kg once a day for 21 days and a single intratracheal injection of BLM at 3.0 mg/kg); and one group received saline (a single intratracheal injection and daily intraperitoneal injections) (page 2, left column, paragraph 4). It was found that TUDCA alleviates BLM-evoked collagen deposition in the mice lungs, thereby treating pulmonary fibrosis.
Table 1. TDCA and TUDCA.
Instant
Formula I
(TDCA)
PNG
media_image1.png
169
639
media_image1.png
Greyscale
Taurourso-
deoxycholic
acid
(TUDCA)
PNG
media_image2.png
180
637
media_image2.png
Greyscale
The difference between the teaching of Tong and the instant application is that Tong teaches a method of treating pulmonary fibrosis with TUDCA and fails to teach a method of using TDCA to treat pulmonary fibrosis.
However, NCT04727320 teaches TUDCA as a treatment option for liver fibrosis. In the prospective study, patients with liver fibrosis took TUDCA orally (250 mg) for half a year, then the expression level of fibrosis-related markers were determined following a liver biopsy (study overview).
One of ordinary skill in the art would be motivated to combine the teachings of Tong and NCT04727320 because they illustrate the broad utility of TUDCA as a treatment option for both pulmonary and hepatic fibrosis. Said skilled artisan would know that fibrosis often develops as a result of chronic inflammatory processes, and natural bile acids would have a reasonable expectation of success in their treatment.
The combined teachings of Tong and NCT04727320 teach TUDCA as a treatment option for fibrosis of both the lung and the liver and fail to teach a method of treating lung fibrosis with TDCA.
However, Seong teaches pharmaceutical compositions comprising the sodium salt of TDCA, a solvate thereof, or a pharmaceutically acceptable salt thereof, for treating metabolic diseases including liver fibrosis (title, technical field). The method of treating liver fibrosis comprises administering to the patient a pharmaceutical composition of Na-TDCA about 0.1 to 100 mg/kg of once or several times per day (page 7, paragraph 1). Seong further teaches that 2.5 mg/kg of Na-TDCA significantly reduces TNF-α plasma levels compared to control (Figure 4B).
One would be motivated to combine the teaching of Seong with the combined teachings of Tong and NCT04727320 because TDCA and TUDCA are related in that they are diastereomeric positional isomers, wherein TDCA is comprised of a hydroxyl group on position A and TUDCA is comprised of the hydroxyl group on position B (Table 1). MPEP 2144.09 states that compounds which are positional isomers are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. Furthermore, Malaviya teaches that increased levels of TNF-α have been linked to a number of pulmonary inflammatory diseases, including interstitial pulmonary fibrosis (IPF) (abstract). Etanercept and Pirfenidone are two examples of TNF-α inhibitors tested as IPF treatment (page 93, Table 1).
Accordingly, a skilled artisan could have applied prong (E) of the KSR rational to select TDCA from the finite list of isolated natural bile acids for a method of treating lung fibrosis with a reasonable expectation of success. In additional consideration that both TUDCA and TDCA are known in the art to treat hepatic fibrosis, one of ordinary skill in the art would have found it prima facie obvious to use TDCA in a method of treating fibrosis of the lungs, thus arriving at the current invention.
Claim 3 is directed to a pharmaceutical composition, wherein the pharmaceutically acceptable salt is a sodium salt.
Seong teaches a method comprised of administering to the patient the sodium salt of TDCA (technical field).
One of ordinary skill in the art would be motivated to combined the teaching of Seong with the teaching of Tong because Seong shows the sodium salt of TDCA is therapeutically effective in treating liver fibrosis and reducing TNF-α plasma levels. Accordingly, there is a reasonable expectation of success that the sodium salt would similarly be effective in treating lung fibrosis.
Claims 4-5 are directed to the method above, wherein the TDCA reduces the expression of factors related to pulmonary fibrosis, wherein said factors are Col1α1, α-SMA, or PAI-1.
Tong teaches α-SMA-positive cells was markedly elevated in the BLM-treated mice and reduced in those treated with TDCA (Figure 2a and Figure 2b). Per, MPEP 2144.09, one of ordinary skill in the art would expect compounds of similar chemical structure to have similar properties. Accordingly, said artisan would expect TDCA to similarly reduce the expression of α-SMA-positive cells.
Claim 6 is directed to the method above, wherein the pulmonary fibrosis is selected from a group of fibrotic diseases.
Tong teaches TUDCA effectively reduces BLM-induced lung fibrosis in mouse models, which is extensively used to test IPF treatment (page 1, paragraph 1). As stated above, one of ordinary skill in the art would expect compounds of similar chemical structure to have similar properties.
Claim 7 is directed to the method above, wherein the method further comprises one or more pharmaceutically acceptable carriers.
Seong teaches the pharmaceutical composition of the TDCA sodium salt may be in the form of capsules, which are dry-filled capsules made of gelatin, and soft, sealed capsules made of gelatin and plasticizers, such as glycerol or sorbitol. Dry-filled capsules may contain active ingredients in the form of particles, such as fillers, such as lactose, binders, starch, and/or lubricating agents, such as talc or magnesium stearate, and, if appropriate, a mixture with stabilizers. In soft capsules, the active ingredient can be dissolved or suspended in an appropriate liquid, such as fatty oil, paraffin oil, or liquid polyethylene glycol, and a stabilizer may be added to it (page 7, paragraphs 4-5).
One of ordinary skill in the art would be motivated combine the teaching of Seong with
Tong because Seong teaches a pharmaceutical composition formulated for TDCA as an effective treatment option for liver fibrosis and reducing TNF-α plasma levels. Accordingly, there is a reasonable expectation of success for the same formulation to treat lung fibrosis.
Conclusions
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/P.A./Examiner, Art Unit 1621
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621
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