Compounds and compositions are disclosed in which a quaternized drug unit is linked to a targeting ligand unit from which a tertiary amine-containing drug is released at the targeted site of action. Methods for treating diseases characterized by the targeted abnormal cells, such as cancer or an autoimmune disease using the compounds and compositions of the invention are also disclosed.

The present invention relates to an improved process of conjugation to obtain synthetic oligosaccharide-protein (OS-PR) conjugates. The process of synthetic OS-PR conjugation is a rapid process providing oligosaccharide-protein conjugates which are highly immunogenic and elicit specific and homogenous immune responses. The synthetic oligosaccharide comprising of four to eight repeating units of respective monomers and at least one in-built terminal amino linker, said synthetic polysaccharide mimics natural polysaccharide obtained from gram negative bacteria such as Neisseria meningitidis serogroups A, C, Y, W, X and Haemophilus influenzae and carrier protein is obtained from gram positive bacteria such as Clostridium tetani (tetanus toxoid) or Corynebacterium diphtheriae (CRM197) or their recombinant versions. The conjugation chemistry of the said oligosaccharide-protein conjugate of the present invention is thio-ether linkage. The present invention takes complete process time in the range of 14-22 hours. The said oligosaccharide-protein conjugates are useful in production of monovalent vaccine or multivalent combination vaccines and as diagnostic tool.

Emerging evidence indicates that diminished activity of the vasoprotective axis of the renin-angiotensin system, constituting angiotensin converting enzyme2 (ACE2) and its enzymatic product, angiotensin-(1-7) [Ang-(1-7)] contribute to pulmonary hypertension (PH). However, clinical success for long-term delivery of ACE2 or Ang-(1-7) would require stability and ease of administration to increase patient compliance. Chloroplast expression of therapeutic proteins enables their bioencapsulation within plant cells to protect from acids and gastric enzymes; fusion to a transmucosal carrier facilitates effective systemic absorption. Oral feeding of rats with bioencapsulated ACE2 or Ang-(1-7) attenuated monocrotaline (MCT)-induced increase in right ventricular systolic pressure, decreased pulmonary vessel wall thickness and improved right heart function in both prevention and reversal protocols. Furthermore, combination of ACE2 and Ang-(1-7) augmented the beneficial effects against cardio-pulmonary pathophysiology induced by MCT administration. Experiments have also been performed which indicate that this approach is also suitable for the treatment or inhibition of experimental uveitis and autoimmune uveoretinitis These studies provide proof-of-concept for a novel low-cost oral ACE2 or Ang-(1-7) delivery system using transplastomic technology for pulmonary and ocular disease therapeutics.

In one aspect, the disclosure provides cross-linked materials that include multivalent lectins with at least two binding sites for glucose, wherein the lectins include at least one covalently linked affinity ligand which is capable of competing with glucose for binding with at least one of said binding sites; and conjugates that include two or more separate affinity ligands bound to a conjugate framework, wherein the two or more affinity ligands compete with glucose for binding with the lectins at said binding sites and wherein conjugates are cross-linked within the material as a result of non-covalent interactions between lectins and affinity ligands on different conjugates. These materials are designed to release amounts of conjugate in response to desired concentrations of glucose. Depending on the end application, in various embodiments, the conjugates may also include a drug and/or a detectable label.

There is provided a method of detecting in a sample the presence of an anti-M and/or anti-A and/or anti-C/Y antibody, the method comprising contacting the sample with a diagnostic conjugate provided according to the invention, comprising an oligosaccharide which comprises at least two units of 4,6-dideoxy-4-acylamido-α-pyranose and comprising at least one -(1-3)-link between adjacent 4,6-dideoxy-4-acylamido-α-pyranose units, in which the carbon at position 5 in the pyranose is linked to an R group, where R is independently selected from —CH.sub.2OH, —H or an alkyl group having at least one C atom, the oligosaccharide being covalently linked to a non-saccharide molecule or to a surface.

Provided are mixed carrier, multivalent pneumococcal conjugate compositions comprising 20 different pneumococcal capsular polysaccharide-protein conjugates, wherein each of the conjugates includes a capsular polysaccharide from a different serotype of Streptococcus pneumoniae conjugated to either tetanus toxoid or CRM.sub.197, wherein the Streptococcus pneumoniae serotypes are selected from 1, 3, 4, 5, 6A, 6B, 7F, 8, 9V, 10A, 11A, 12F, 14, 15B, 18C, 19A, 19F, 22F, 23F, and 33F, wherein two of the capsular polysaccharides are conjugated to tetanus toxoid and the remaining capsular polysaccharides are conjugated to CRMig7, and wherein the two capsular polysaccharides that are conjugated to tetanus toxoid are selected from the group consisting of serotypes 1, 3, and 5. Also provided are methods of producing the mixed carrier, multivalent pneumococcal conjugate compositions and methods of using the same for prophylaxis against Streptococcus pneumoniae infection or disease in a subject.

The present invention relates to synthetic saccharides of general formula (I) that are related to Streptococcus pneumoniae serotype 8 capsular polysaccharide, conjugates thereof and the use of said saccharides and conjugates for raising a protective immune response in a human and/or animal host. Furthermore, the synthetic saccharide structures of general formula (I) are useful as marker in immunological assays for detection of antibodies against Streptococcus pneumoniae bacteria.

In an embodiment of the invention, a composition for treating a cell population comprises an Affinity Medicant Conjugate (AMC). The medicant moiety can be a toxin including an acylfulvene or a drug moiety. The affinity moiety can be an antibody, a binding protein, a steroid, a lipid, a growth factor, a protein, a peptide or non peptidic. The affinity moiety can be covalently bound to the medicant via a linker. Novel linkers that can be directed to cysteine, arginine or lysine residues based on solution pH allow greater flexibility in preserving and/or generating specific epitopes in the AMC.

Provided is an immunogenic composition comprising 15 different polysaccharide-protein conjugates. Each of the conjugates comprises a capsular polysaccharide prepared from different serotype Streptococcus pneumoniae conjugated to a carrier protein, that is, serotypes 1, 2, 3, 4, 5, 6A, 6B, 7F, 9N, 9V, 14, 18C, 19A, 19F and 23F. An immunogenic composition formulated into a vaccine comprising an aluminum-based adjuvant increases application range with respect to pneumococcal diseases in infants and children.

The disclosure relates to methods of identifying fragments of a polypeptide that are immunogenic for a specific human subject, methods of preparing personalised pharmaceutical compositions comprising such polypeptide fragments, human subject-specific pharmaceutical compositions comprising such polypeptide fragments, and methods of treatment using such compositions. The methods comprise identifying a fragment of the polypeptide that binds to multiple HLA of the subject.