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 .
Priority
This application claims the benefit of and priority to Application No. CN 202210863481.3, filed July 20, 2022, is acknowledged.
Information Disclosure Statement
No disclosure statement has been filed.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 7 and 10 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Fasan and Owens US20210115087A1.
Regarding claim 7, the reference Fasan and Owens anticipates the prevention or treating of vasculitis caused by endothelial injury comprising the administration of a smoothened (SMO) inhibitor, specifically a cyclic peptide SMO inhibitor. The art identifies (¶307) where Hedgehog pathway inhibitors may be used in the treatment or prevention of inflammatory disease with specific mention to vasculitis and included in the group of related diseases/disorders where there are known causes of endothelial injury (damage to the vessels inner lining) from cancer, autoimmune disease, cardiovascular disease/compromise and other inflammatory diseases. It is further established (¶401) where additional examples of suppression to SHh/Hedgehog pathway signaling pathways are validated by experiment, the use of SMO inhibitor, specifically cyclopamine to cause full inhibition of the SHh/Hedgehog pathway.
Regarding claim 10, the reference Fasan and Owens anticipates the increasing of the inner diameter of the blood vessel with a smoothened (SMO) inhibitor, specifically a cyclic peptide SMO inhibitor. The art identifies (¶312) where suppression of Hedgehog signaling has been found to be beneficial for improving blood vessel density and blood vessel patency. Additional notation has been given to the increased potentials of procedural administrations such as cancer drug and/or imaging contrasting agents (CAT/MRI) administration.
Claim Rejections - 35 USC § 103
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.
Claim(s) 1-6 are rejected under 35 U.S.C. 103 as being unpatentable over Fasan and Owens US20210115087A1 and further in view of Song et al, PDGFRA in vascular adventitial MSCs promotes neointima formation in arteriovenous fistula in chronic kidney disease, JCI Insight, 5(21), 2020.
The reference art, Fasan and Owens teaches the relationship between smoothened (SMO) tissue and the Hedgehog (Hh)/Sonic Hedgehog (SHh) signaling pathways for the treatment of various disease types like inflammatory diseases or neoplasms. Specifically, where increased signaling activity of the Hh pathway antagonizes the smoothened (SMO) gene and increasing downstream signaling. In reference to claims 2-3, Fasan and Owens notes and cites multiple references (within the primary art) where cyclopamine, vismodegib and/or the combination of drugs used to target additional Hh pathway mechanisms (¶318). In addition, Fasan and Owens has further demonstrated (¶401) where the inhibitor cyclopamine was tested and validated the full inhibition of a SHh pathway signaling pathway. The reference art further teaches where the dosage form of the drug comprises a solution, a tablet, a capsule or a granule. The reference art demonstrates where modes of formulation be dependent based on the needs of the subject or desired means of administration (¶337) as identified in claim 4. Finally, the reference art teaches wherein the drug comprises a pharmaceutically acceptable adjuvant and comprises any one combination of at least two of a diluent, disintegrant, flavoring agent, adhesive, excipient or a filler. The reference art demonstrates (¶338) where the acceptable adjuvants referenced in claims 5-6, to be used in compression or molding for the purposes of making a tablet. Fasan and Owens however, do not teach the preventing, delaying or alleviating access stenosis of an arteriovenous fistula (AVF).
Song teaches (pp2, Results ¶1) where the association with the Hh signaling pathway in AVFs from patients with end-stage renal disease detected small lumen and thicker walls of the AVF. Whereas, it is known within the art and further identified (pp7, Discussion, ¶1) where decreases in the diameter of the lumen further decreases the vessels’ ability to relax or maintain flexibility, decrease vascularization, increase blood pressure and increase the risk of blockages.
Therefore, it would haven obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to arrive at the instantly claimed invention for claim 1, where the method for the preventing, delaying or alleviating access stenosis of the arteriovenous fistula for the following reasons:
Per MPEP § 2143(I)(G), a prima facie case of obviousness exists where some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention. It would have been obvious and well within the ordinary skill in the art that one would administer a Smoothened (SMO) inhibitor and/or combination of inhibitors to prevent, delay or alleviate stenosis of the arteriovenous fistula. As previously mentioned, where Fasan and Owens do not specifically mention the stenosis occurring within the arteriovenous venous fistula (AVF), however, Song et al does identify that the subjects experiencing the need for dialysis treatment, where the AVF provides superior access compared to other known interventions. Additionally, Song et al notes the relationship between smoothened (SMO) tissue development within the vessels and the neointima (smooth tissue injury) formation in AVFs which includes the use of a SMO inhibitor because Song et al further links the impacts of targeting the Hh/SHh signaling pathways as the mechanism to target the smoothened tissue to prevent/limit formations within AVFs that cause stenosis and/or restenosis of the vessel.
Claims 8-9 and 11-12 are rejected under 35 U.S.C. 103 as being unpatentable over Fasan and Owen as applied to claim 7 and 10 above.
Fasan and Owens teaches where the use of cyclic peptide Hedgehog inhibitors may be used in the treatment and/or prevention of various disease processes to include inflammatory diseases such as vasculitis (¶307) as relative to the downstream regulation of smoothened (SMO) tissue. Additionally, the authors further note where cyclopamine and/or the combination of drugs (such as SHh inhibitors) are administered as smoothened (SMO) agonists to target additional Hh pathways. Specifically, it notes (¶318) where the Hedgehog pathway can be used in combination with compounds provided to include SMO antagonists such as cyclopamine, additionally listed small molecules to include an the SHh inhibitor robotnikinin (vismodegib is also a SHh inhibitor). Fasan and Owens does mention that targeting of SMO tissue by way of the Hedgehog signaling pathways for prevention and treatment of inflammatory diseases which mentions vasculitis specifically, but the reference art does not specifically state where cyclopamine, vismodegib or glasdegib were administered for the treatment of vasculitis or disclose where the administration of cyclopamine, vismodegib or glasdegib, was administered increases the diameter of the vessel.
Therefore, it would haven obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to arrive at the instantly claimed invention for claims 8-9 and claims 11-12, wherein the SMO inhibitor comprises any one or a combination of at least two of cyclopamine, vismodegib or glasdegib and where the SMO inhibitor comprises cyclopamine for the following reasons:
Regarding claims 8-9, Fasan and Owens reference the therapeutic potential to the targeting of the Hedgehog (Hh) pathways and SMO receptors where they cited additional researchers that mentioned that cyclopamine and vismodegib being the 1st FDA approved Hh pathway antagonists. While Fasan and Owens directly make reference to a cyclic peptide inhibitor that acts on the Hh pathway to impact smoothened (SMO) tissues, there is additional reporting as to the role that SMO inhibitors play regarding Hh/SHh downstream regulation. Therefore, someone skilled in the art would reasonably conclude that to further impact smoothened (SMO) tissue development downstream, that one would replace the cyclic peptide inhibitor from the reference art with a SMO inhibitor because cyclopamine is well known in the art to primarily target the Hh pathway to regulate downstream mechanisms and impact the development of smoothened (SMO) tissue. In addition to replacing the cyclic peptide inhibitor with an SMO inhibitor, it would have been further obvious to have included cyclopamine, vismodegib or glasdegib with the cyclic peptide inhibitor and have the reasonable expectation that the vasculitis would have been treated with the combination of the two compositions that are useful for the same purpose.
Regarding claims 11-12, as previously referenced, Fasan and Owens referemce that the Hedgehog (Hh) pathway can be targeted to further regulate (specifically suppress) the downstream mechanism to impact the development of smoothened (SMO) tissue, where the benefit is demonstrated as improved blood vessel density and patency (¶312). Therefore, someone skilled in the art would reasonably conclude that to further impact smoothened (SMO) tissue development downstream, that one would replace the cyclic peptide inhibitor from the reference art with a SMO inhibitor because cyclopamine is well known in the art to primarily target the Hh pathway to regulate downstream mechanisms and impact the development of smoothened (SMO) tissue. In addition to replacing the cyclic peptide inhibitor with an SMO inhibitor, it would have been further obvious to have included cyclopamine, vismodegib or glasdegib with the cyclic peptide inhibitor and have the reasonable expectation that the vasculitis would have been treated with the combination of the two compositions that are useful for the same purpose.
Summary of the Claims
Claims 1-12 are pending.
Claims 1-12 are rejected.
No claim is in condition for allowance.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to STEVE DROUIN whose telephone number is (571)272-5426. The examiner can normally be reached Monday- Friday 7:30am-5:00pm.
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, Kortney Klinkel can be reached at 571-270-5239. 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.
/S.H.D./Examiner, Art Unit 1627
/Kortney L. Klinkel/Supervisory Patent Examiner, Art Unit 1627