PATENT CLAIM ANALYSIS

Application Number: 15753552
Application Type: Utility
Filing Date: 2018-02
Publication Date: 2018-08
Patent Classification: ["514", "04400A"]

Abstract:
A novel delivery system for drugs, and especially macromolecules such as proteins or oligonucleotides through biological membranes is provided, and specifically delivery of siRNA. The delivery system comprises conjugation of the macromolecule drug to a moiety that enables effective passage through the membranes. Respectively, novel compounds and pharmaceutical compositions are provided, utilizing said delivery system. In one aspect of the invention, the compounds may be utilized in medical practice, for example, in delivery of siRNA or antisense oligonucleotides across biological membranes for the treatment of medical disorders.

Claim (Index 4):
A method for delivery of a drug across biological membranes, the method comprising utilization of a Conjugate, having the structure as set forth in Formula (I): or pharmaceutically acceptable salts, hydrates, solvates and metal chelates of the compound represented by the structure as set forth in Formula (I), and solvates and hydrates of the salts, wherein: D is the drug to be delivered across biological membranes, selected from a group consisting of a small-molecule drug, a peptide, a protein, and a native or modified, single-stranded or double-stranded DNA or RNA, siRNA or ASO; y, z and w are each an integer, independently selected from 0, 1, 2, 3, 4, 5 or 6, wherein whenever the integer is 0, it means that the respective E moiety is null; at least one of y, z or w is different from 0; E, E\u2032, or E\u2033 can be the same or different, each having the structure as set forth in general Formula (II):\n (A) a -B-L 1 -Q 1 -L 2 -Q 2 -L 3  \u2003\u2003Formula (II) \n wherein each A moiety is independently selected from the structures as set forth in Formulae (III), (IV), (V) and (VI): M is selected from null, \u2014O\u2014 or \u2014CH 2 \u2014; and g, h and k are each individually an integer selected from the group consisting of 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 and 16; * is \u2014H, or a point of linkage to B, or to another A group; a is an integer, selected from 1, 2, 3 or 4; Q is oxygen or amine. wherein B is selected from one or more groups consisting of: a linear, cyclic or branched C 1 , C 2 , C 3 , C 4 , C 5 , C 6 , C 7 , C 8 , C 9 , C 10 , C 11 , C 12 , C 13 , C 14 , alkyl or hetero-alkyl, wherein each is optionally substituted by one or more halogen, hydroxyl, methoxy, fluorocarbon, amine or thiol; or optionally linked to an ether, an ester, or an amide group; linear, cyclic or branched C 2 , C 3 , C 4 , C 5 , C 6 , C 7 , C 8 , C 9 , C 10 , C 11 , C 12 , C 13 , C 14  alkylene or heteroalkylene, wherein each is optionally substituted by one or more halogen, hydroxyl, methoxy, fluorocarbon, amine or thiol; or optionally linked to an ether, an ester, or an amide group; C 5 , C 6 , C 7 , C 8 , C 9 , C 10 , C 11 , C 12 , C 13 , C 14  aryl or heteroaryl, wherein each is optionally substituted by one or more halogen, hydroxyl, methoxy, fluorocarbon, amine thiol; or optionally linked to an ether, an ester, or an amide group; one or more steroid moiety, selected from the group consisting of cholesterol, bile acid, estrogen, estradiol, estriol, lithocholic acid or any analog thereof; or any combination thereof, wherein each is optionally substituted by one or more halogen, hydroxyl, methoxy, fluorocarbon, amine or thiol; or each is optionally linked to an ether, an ester, an amine, or an amide group; and any combination thereof; Q 1  and Q 2  are each a cleavable group, independently selected from null, ester, thio-ester, amide [e.g., \u2014C(\u2550O)\u2014NH\u2014 or \u2014NH\u2014C(\u2550O)\u2014], carbamate [e.g., \u2014O\u2014C(\u2550O)\u2014NH\u2014 or \u2014NH\u2014C(\u2550O)\u2014O\u2014], urea [\u2014NH\u2014C(\u2550O)\u2014NH\u2014], disulfide [\u2014(S\u2014S)\u2014], ether [\u2014O\u2014], amine, imidazole, triazole, dilactone; a metal chelator selected from BAPTA and EGTA, including its chelated metal ion; and any combinations thereof; L 1 , L 2  and L 3  are each independently selected from null and the group consisting of: linear, cyclic or branched C 1 , C 2 , C 3 , C 4 , C 5 , C 6 , C 7 , C 8 , C 9 , C 10 , C 11 , C 12 , C 13  or C 14 , alkyl or hetero-alkyl, wherein each is optionally substituted by one or more halogen, hydroxyl, methoxy, fluorocarbon, amine, or thiol; or linked to an ether group; linear, cyclic or branched C 2 , C 3 , C 4 , C 5 , C 6 , C 7 , C 8 , C 9 , C 10 , C 11 , C 12 , C 13  or C 14  alkylene or heteroalkylene, wherein each is optionally substituted by one or more halogen, hydroxyl, methoxy, fluorocarbon, amine, thiol; or linked to an ether group; C 5 , C 6 , C 7 , C 8 , C 9 , C 10 , C 11 , C 12 , C 13  or C 14  aryl or heteroaryl, wherein each is optionally substituted by one or more halogen, hydroxyl, methoxy, fluorocarbon, amine, thiol; or linked to an ether group; \u2014(O\u2014CH 2 \u2014CH 2 ) u \u2014, wherein each is optionally substituted by one or more halogen, hydroxyl, methoxy, fluorocarbon, amine, or thiol; nucleoside, nucleotide; imidazole, azide, acetylene; and any combinations thereof, wherein each is optionally substituted by one or more halogen, hydroxyl, methoxy, fluorocarbon, amine, thiol; or linked to an ether group; and wherein u is an integer of 1, 2, 3, 4 or 5; and any combinations thereof; wherein at least one of Q 1 , Q 2 , L 1 , L 2  and L 3  is not null, and wherein each of Q 1 , Q 2 , L 1 , L 2  and L 3  optionally comprises a T moiety; wherein T is an initiator group, selected from C 4 , C 5 , C 6 -1,2-dithiocycloalkyl (1,2-dithiocyclo-butane; 1,2-dithiocyclo-pentane; 1,2-dithiocyclohexane; 1,2-dithiocycloheptane); \u03b3-Lactam (5 atoms amide ring), \u03b4-Lactam (6 atoms amide ring) or \u03b5-Lactam (7 atoms amide ring); \u03b3-butyrolactone (5 atoms ester ring), \u03b4-valerolactone (6 atoms ester ring) or \u03b5-caprolactone (7 atoms ester ring); wherein each is optionally substituted by one or more halogen, hydroxyl, methoxy, fluorocarbon, amine, or thiol; wherein at least one of B, Q 1 , Q 2 , L 1 , L 2  and L 3  is conjugated to a drug as defined in Formula (I).

Metadata:
- Claim Count in Document: 6.0
- Percentile: 88.0
- Lexical Diversity: 1.66102
- Patent Class: 514.0
- Transitional Phrase Type: open
- Component Type: 1
- Foreign Priority: False
- Related Applications: ['15222559', '14872179', '14830799', '15691821', '14690499']

Analysis Scores:
- 35 USC 101 Eligibility (BERT): 0.8034805001948623
- 35 USC 102 Novelty (BERT): 0.6169355718752508
- Combined Prediction Score: 0.7848260073629012
- Mean Citation Score: 441.934864
- Max Citation Score: 574.69934
- Similarity Product: 517.6288711927557

Labels:
- Claim Label 101: 1
- Claim Label 102: 0
- Claim Label 103: 1
- Claim Label 112: 1
- Combined Label: 0
- Label 101 Adjusted: 1

Dataset: test