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
Filing Receipt and Priority
The filing receipt mailed 04/10/2024 states that the instant application is a 371 of PCT/EP2021/057609, filed 03/24/2021.
The PCT document supports the instant claims. Therefore, the effective filing date is 03/24/2021.
A certified copy of the foreign priority application has not been provided.
Information Disclosure Statement
The information disclosure statement (IDS) submitted 09/22/2023 has been considered.
Specification
Objection
Compounds displayed in the specification are difficult to read. Example shown below.
PNG
media_image1.png
214
542
media_image1.png
Greyscale
If possible, examiner suggests increasing the size of the table and/or compounds.
Additionally, the table within the specification appears to be missing compound structures or the structure does not fit within the table as shown below.
PNG
media_image2.png
157
682
media_image2.png
Greyscale
PNG
media_image3.png
224
624
media_image3.png
Greyscale
Claim Objections
Claim 5 states “The compound of claim 1, wherein when A is 5-6 membered heteroaryl, wherein said 5-6 membered heteroaryl…”. The first use of “when” is not needed. Similar language is in claim 6.
Rejections
Claim Rejections - 35 USC § 112(a)
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 11-13 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for idiopathic pulmonary fibrosis and pulmonary fibrosis, does not reasonably provide enablement for all diseases, disorders or conditions associated with dysregulation of lysophosphatidic acid receptor 2 (LPA2) receptor or all fibrosis types. 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 these claims.
The following Wands Factors have been considered if not explicitly discussed:
(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.
Breadth of the claims
Claim 11 reads “A method of treating a disease, disorder, or condition associated with dysregulation of lysophosphatidic acid receptor 2 (LPA2) comprising administering to a patient in need thereof a therapeutically effective amount of the compound of claim 1.”
Claim 12 reads A method of treating fibrosis comprising administering to a patient in need thereof a therapeutically effective amount of the compound of claim 1.”
Claim 13 specifies fibrosis types which includes pulmonary fibrosis, idiopathic pulmonary fibrosis (IPF), hepatic fibrosis, renal fibrosis, ocular fibrosis, cardiac fibrosis, arterial fibrosis and systemic sclerosis.
Nature of the invention
The invention is drawn to clinical methods of treating diseases, disorders, or conditions and/or specific fibrosis types.
State of the prior art
The compounds are novel as discussed in the allowable subject matter section below. The closest art, found in Beck (Bioorganic & Medicinal Chemistry Letters, 18, 2008, 1037-1041, of the record), teaches compounds of structure shown below
PNG
media_image4.png
164
142
media_image4.png
Greyscale
PNG
media_image5.png
172
330
media_image5.png
Greyscale
Beck identifies the compounds as potent LPA2 Receptor inhibitors but does not discuss or teach diseases, disorders, or conditions related to LPA2 or any specific fibrosis types.
Yung (Journal of Lipid Research, vol. 55, 2014, of the record) discusses the connection between LPA2 and fibrosis. Yung, on p. 1202, sec. Fibrosis states “Lpar2 may also be involved in pulmonary fibrosis, as knockout mice demonstrated protection against bleomycin-induced lung injury, fibrosis, and death.”
Geraldo (Signal Transduction and Targeted Therapy, 2021, 6:45) discusses the connection between general LPA signaling and certain conditions. Geraldo in sec. LPA and Neurodegenerative Diseases connects LPAR2 to traumatic brain injury (TBI), but does not disclose any evidence or data that would suggest that LPA2 inhibition is effective treatment for TBI. Similarly, Geraldo discusses cancer, neuropathic pain, central nervous system development and angiogenesis but does not explicitly discuss any data that would suggest treatment using a LPA2 inhibitor would be effective treatment.
Amount of direction provided and working examples
The instant specification on p. 115 -119 discusses in vitro assays that show many of the claimed compounds have affinity LPA-2. The instant specification does not disclose any tests or data indicating efficacy in treating conditions however.
The instant specification discusses LPA signaling and pulmonary fibrosis on p. 5, l. 5. LPA2 antagonists as potential anticancer medications are discussed on p. 6, l. 4-8. However, this discussion is only contemplative.
Level of predictability and quantity of experimentation
Considering the state of the art, there is already a level of unpredictability should one of ordinary skill attempt to practice a method for treating general diseases, disorders, or conditions using general LPA2 receptor inhibitors. As the compounds are novel, there is nothing indicating their efficacy in methods to treat general fibrosis, including hepatic fibrosis, ocular fibrosis, cardiac fibrosis, arterial fibrosis, and systemic sclerosis. Therefore, there is a significant level of unpredictability and an undue burden of experimentation placed on one of ordinary skill in the art should they attempt to practice the claimed methods.
Allowable Subject Matter
Claims 1-9 and 15-21 are allowed. The closest art in Beck (cited above) teaches compounds of similar structure to the claimed compounds. However, the critical difference is the B group in the instant claims which is not taught or made obvious by Beck. The B group claimed is discussed in Armani (J. Med. Chem. 2023, 66, 5622-5656). Armani on p. 5633, Table 8 discloses compounds substituted at the C8 position. Armani in sec. Conclusions states “While changes to the linker led only to inactive compounds, combining the best results obtained from the RHS and core modifications, we identified compound 58, a highly potent and selective LPA2 receptor antagonist, with a good oral PK profile in mouse. The eD2M for compound 58 was calculated to be 0.05 mg/kg/day, which represents a 45000-fold improvement compared to the starting compound AMG35….”.
Claim 14 is objected to for being drawn to allowable subject matter but dependent on a rejected claim.
Conclusion
Claims 1-9 and 15-21 allowed.
Claims 14 are objected to.
Claim 11-13 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LUISALBERTO GONZALEZ whose telephone number is (571)272-1154. The examiner can normally be reached M-F 8:30-5:30.
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, Jeffrey Murray can be reached at (571) 272-9023. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/L.G./Examiner, Art Unit 1624
/SUSANNA MOORE/Primary Examiner, Art Unit 1624
Prosecution Insights