DETAILED ACTION
STATUS OF THE APPLICATION
Receipt of the response to the final office action, the amendments to the claims and applicant arguments/remarks, filed 12/01/2025 is acknowledged.
Claims 1-3, 13,16-18, and 29-32, are pending in this action. No new matter was added. Claims 1-3, 13, 16-18, and 29-32 are currently under consideration.
Any rejection or objection not reiterated in this action is withdrawn. Applicant’s amendments necessitated new ground(s) of rejection or objection presented in this office action.
The present application, filed on or after June 01, 2022, is being examined under the first inventor to file provisions of the AIA . 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.
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.
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.
Claims 1-3, 13, 16-18 and 29-32, are rejected under 35 U.S.C. 103 as being unpatentable over Deli (Potential use of tight junction modulators to reversibly open membranous barriers and improve drug delivery, Biochimica et Biophysica Acta 1788 (2009) 892-910).
Regarding claims 1-3, 17, and 18, Deli teaches E-cadherin has been shown to be present in brain endothelial cells and is found in all epithelial barriers. Loss of E-cadherin activates Rac, a small GTPase of the Rho family, and protein kinase C (PKC), which changes the location of claudin-1, -4, and zonula occludens-1 at tight junctions and enhances tight junction permeability. E-cadherin loss or downregulation is a crucial step in the invasion and metastasis of cancer. The lobular breast cancer, familial gastric cancer, and human gastric carcinoma cell line have all been found to have mutations in CDH1 that impair the adhesive function of E-cadherin (See page 4-5, 3.2). The reference also teaches according to ongoing multicenter clinical investigations, intraarterial hyperosmotic mannitol can improve the penetration of anticancer medications and increase survival in patients with malignant brain tumors by disrupting the blood-brain barrier (See page 14, 6.2).
Regarding claim 16, Deli teaches peptides produced from Zonula occludens toxin or clostridium perfringens enterotoxin, peptides chosen by phage display that bind to integral membrane tight junction proteins, and lipid modulators are examples of modulators that directly affect tight junctions. They have the potential to be employed as pharmaceutical excipients to enhance drug delivery across blood-brain and epithelial barriers. They can also reversibly increase paracellular transport and drug delivery with less toxicity than earlier absorption enhancers (See Abstract). The reference also teaches the non-toxic, biocompatible polymeric absorption enhancers chitosan and its variants are derived from chitin. As excipients for drug delivery across the gastrointestinal, pulmonary, and cutaneous epithelial barriers, these cationic polysaccharides have been investigated due to their mucoadhesive and absorption-enhancing qualities (See page 11, 5.4). The reference also teaches oleic acid is a widely used absorption enhancer that is utilized in microemulsions, patches, and transdermal drug delivery systems. It is well recognized to alter membrane structure (See page 11, 5.2). The reference also teaches protein kinase C is activated by calcium chelators such as EDTA, which disrupt adherens junctions and tight junctions to promote paracellular permeability (See page 10, 5.1).
Regarding claims 13, and 29-32, Deli discloses that keratin-filled corneocytes in a special lipid matrix make up the stratum corneum, the outermost layer. The poor permeability to water and solutes is caused by this layer. Although skin acts as a major barrier to drug transport, trandermal drug delivery is the most efficient non-oral technique for systemic drug delivery available in the pharmaceutical industry (See page 3, 2.3). The reference also explains how calcium chelators, including ethylenediamine-N, -N, -N, -N-tetraacetic acid (EDTA), increase paracellular permeability by breaking adherens junction and tight junctions by activating protein kinase-C (See page 10, 5.1). the intricate structures called tight junctions, which close the paracellular gaps between the cells of the mammalian epithelial and endothelial barriers, are also covered in the reference, and the made up of signaling molecules that allow the dynamic regulation of paracellular transport, integral membrane proteins, and linker or adaptor proteins that connect them to the actin cytoskeleton (See page 3, 3.0).
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Kimberly Barber whose telephone number is (703) 756-5302. The examiner can normally be reached on Monday through Friday from 6:30 AM to 3:30 PM EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Robert A. Wax, can be reached at telephone number (571) 272-0623. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KIMBERLY BARBER/Examiner, Art Unit 1615
/Robert A Wax/Supervisory Patent Examiner, Art Unit 1615