Abstract: This application provides novel bispecific antigen-binding antibodies, and antigen-binding fragments thereof, that bind to both HER2 and Trop-2. These bispecific anti-HER2/Trop-2 antibodies comprise a first antigen-binding domain that specifically binds human HER2 or Trop-2, and a second antigen-binding domain that specifically binds human Trop-2 or HER2. The bispecific antibodies have high binding affinity for HER2 and Trop-2, can be internalized by cells expressing HER2 and/or Trop-2. The bispecific antibody-drug conjugates (ADC) are capable of inhibiting the growth of tumors cells expressing HER2 and/or Trop-2 in vitro and in vivo. The bispecific antibodies can be used to diagnose, prognose, and treat HER2- and/or Trop-2-associated human diseases (e.g., cancer, infectious diseases, autoimmune diseases, asthma, transplant rejection, and inflammatory disorders).

Abstract: The present invention describes novel maytansinoid and ansamitosin derivatives and methods for preparing payloads thereof bearing a linker with a functional group for conjugation to cell binding agents to generate cytotoxic drug conjugates. The present invention further relates to antibody drug conjugates conjugated to tumor associated antigen (TAA) antibody, preparation methods, pharmaceutical compositions and uses thereof for the treatment of cancer. The maytansinoid drug linker derivative payloads show increased solubility with decreased aggregation rate compared SMCC-DM1. An antibody drug conjugate containing a maytansinoid drug linker derivative payload and an anti-T rop-2 antibody (e.g., anti-T rop-2-BI-P203) was more or equally potent against Trop-2 high expressing tumors as compared to anti-T rop-2-SMCC-DM 1 or anti-T rop-2-vc-MMAE ADCs, with less effect on low or no antigen expressing cells, suggesting an increased therapeutic window.

Abstract: Disclosed are P-stereogenic groups that may be used in the synthesis of compounds including stereochemically enriched P-stereogenic phosphorothioates. P-stereogenic groups may be provided in nucleoside phosphoramidites including a sugar bonded to a nucleobase and to a stereochemically enriched phosphoramidite as well as methods of their use and methods of making them.

Abstract: This application provides isolated antibodies, and antigen-binding fragments thereof, that specifically bind Trophoblast Cell-Surface Antigen-2 (Trop-2). These Trop-2 antibodies, or antigen-binding fragments thereof, have a highbinding affinity for Trop-2, are capable of inducing antibody- dependent cell-mediated cytotoxicity (ADCC), have good tumor penetration, can be internalized by cells expressing Trop-2, and can be used to diagnose, prognose, and treat Trop-2 -associated human diseases (e.g., cancer, infectious diseases, autoimmune diseases, asthma, transplant rejection, and inflammatory disorders).

Abstract: Disclosed are chiral phosphoramidite auxiliary compositions for diastereoselective synthesis of stereochemically enriched oligonucleotides, and nucleoside phosphoramidite compounds comprising the same. Exemplary structures of the chiral phosphoramidite auxiliary compositions include Formulas (IA) and (IB).

Abstract: Immunomodulating polynucleotides are disclosed. The immunomodulating polynucleotides may contain 5-modified uridine, 5-modified cytidine, a total of from 6 to 16 nucleotides, and/or one or more abasic spacers and/or internucleoside phosphotriesters. Also disclosed are conjugates containing a targeting moiety and one or more immunomodulating polynucleotides. The immunomodulating polynucleotides and conjugates may further contain one or more auxiliary moieties. Also disclosed are compositions containing the immunomodulating polynucleotides or the conjugates containing one or more stereochemically enriched internucleoside phosphorothioates. Further disclosed are pharmaceutical compositions containing the immunomodulating polynucleotides or the conjugates and methods of their use.

Abstract: Immunomodulating polynucleotides are disclosed. The immunomodulating polynucleotides may contain 5-modified uridine, 5-modified cytidine, a total of from 6 to 16 nucleotides, and/or one or more abasic spacers and/or internucleoside phosphotriesters. Also disclosed are conjugates containing a targeting moiety and one or more immunomodulating polynucleotides. The immunomodulating polynucleotides and conjugates may further contain one or more auxiliary moieties. Also disclosed are compositions containing the immunomodulating polynucleotides or the conjugates containing one or more stereochemically enriched internucleoside phosphorothioates. Further disclosed are pharmaceutical compositions containing the immunomodulating polynucleotides or the conjugates and methods of their use.

Abstract: The invention features a hybridized polynucleotide construct containing a passenger strand, a guide strand loadable into a RISC complex, and (i) a 3?-terminal or an internucleotide non-bioreversible group in the guide strand; or (ii) a 5?-terminal, a 3?-terminal, or an internucleotide non-bioreversible group in the passenger strand, and a 5?-terminal, a 3?-terminal, or an internucleotide disulfide bioreversible group in the guide strand or the passenger strand. The invention also features methods of delivering a polynucleotide to a cell using the hybridized polynucleotide construct. The invention further features methods of reducing the expression of a polypeptide in a cell using the hybridized polynucleotide construct.

Abstract: Disclosed are P-stereogenic groups that may be used in the synthesis of compounds including stereochemically enriched P-stereogenic phosphorothioates. P-stereogenic groups may be provided in nucleoside phosphoramidites including a sugar bonded to a nucleobase and to a stereochemically enriched phosphoramidite as well as methods of their use and methods of making them.

Abstract: The invention features a hybridized polynucleotide construct including a passenger strand, a guide strand loadable into a RISC complex, and one or more auxiliary moieties. At least one of the auxiliary moieties is non-bioreversibly linked to an internucleoside phosphate or phosphorothioate in the passenger strand. The invention further features methods of delivery a polynucleotide construct to a cell and methods of reducing the expression of a protein in a cell. The methods typically involve contacting the cell with the hybridized polynucleotide construct.

Abstract: The invention features a mononucleotide comprising a nucleobase bonded to a sugar having a 3?-carbon and a 5?-carbon, where the 5?-carbon is bonded to a phosphorus (V) atom of a phosphate group through an oxygen atom, the phosphorus (V) atom being bonded to (i) a disulfide bioreversible group through an oxygen atom; and (ii) (a) optionally substituted amino, optionally substituted alkoxy, optionally substituted aryloxy, or optionally substituted heteroaryloxy; or (b) the 3?-carbon through an oxygen atom. The invention also features methods of delivering the mononucleotide to a cell and methods of treating a subject having Hepatitis C.

Abstract: Immunomodulating polynucleotides are disclosed. The immunomodulating polynucleotides may contain 5-modified uridine, 5-modified cytidine, a total of from 6 to 16 nucleotides, and/or one or more abasic spacers and/or internucleoside phosphotriesters. Also disclosed are conjugates containing a targeting moiety and one or more immunomodulating polynucleotides. The immunomodulating polynucleotides and conjugates may further contain one or more auxiliary moieties. Also disclosed are compositions containing the immunomodulating polynucleotides or the conjugates containing one or more stereochemically enriched internucleoside phosphorothioates. Further disclosed are pharmaceutical compositions containing the immunomodulating polynucleotides or the conjugates and methods of their use.

Abstract: A district public water supply pipe network system compatible for ground source heat pump water and reclaimed water comprises a water supply main pipe connected with a reclaimed water outlet side of a sewage treatment system and connected to a plurality of energy stations and a plurality of transmission and distribution station, and a return water main pipe arranged between the adjacent energy stations to connect them. The energy stations are provided with a plurality of shallow geothermal heat exchange system for exchanging heat with shallow geothermal energy in the region. Both the energy stations and the transmission and distribution station are connected with corresponding distribution pipe networks connected with a user terminal water supply system. The system provides the source side water and the reclaimed water to users. It is a district public geothermal pipe network and a reclaimed water pipe network.

Abstract: The invention features a hybridized polynucleotide construct containing a passenger strand, a guide strand loadable into a RISC complex, and (i) a 3?-terminal or an internucleotide non-bioreversible group in the guide strand; or (ii) a 5?-terminal, a 3?-terminal, or an internucleotide non-bioreversible group in the passenger strand, and a 5?-terminal, a 3?-terminal, or an internucleotide disulfide bioreversible group in the guide strand or the passenger strand. The invention also features methods of delivering a polynucleotide to a cell using the hybridized polynucleotide construct. The invention further features methods of reducing the expression of a polypeptide in a cell using the hybridized polynucleotide construct.

Abstract: The invention features polynucleotide constructs containing one or more components (i) containing a disulfide linkage, where each of the one or more components is attached to an internucleotide bridging group or a terminal group of the polynucleotide construct, and each of the one or more components (i) contains one or more bulky groups proximal to the disulfide group. The invention also features polynucleotide constructs containing one or more components (i) containing a disulfide linkage, where each of the one or more components (i) is attached to an internucleotide bridging group or a terminal group of the polynucleotide construct, and each of the one or more components (i) contains at least 4 atoms in a chain between the disulfide linkage and the phosphorus atom of the internucleotide bridging group or the terminal group; and where the chain does not contain a phosphate, an amide, an ester, or an alkenylene.

Abstract: A district public water supply pipe network system compatible for ground source heat pump water and reclaimed water comprises a water supply main pipe connected with a reclaimed water outlet side of a sewage treatment system and connected to a plurality of energy stations and a plurality of transmission and distribution station, and a return water main pipe arranged between the adjacent energy stations to connect them. The energy stations are provided with a plurality of shallow geothermal heat exchange system for exchanging heat with shallow geothermal energy in the region. Both the energy stations and the transmission and distribution station are connected with corresponding distribution pipe networks connected with a user terminal water supply system. The system provides the source side water and the reclaimed water to users. It is a district public geothermal pipe network and a reclaimed water pipe network.

Abstract: The present invention provides methods of treating (including preventing) a disease or condition associated with abnormal angiogenesis in a subject include administering a therapeutically effective amount of an AA targeting compound of the invention to the subject. The AA targeting compounds comprise AA targeting agent-linker conjugates which are linked to a combining site of an antibody.

Abstract: The present invention provides various uses of VEGF binding peptides, including methods to treat disorders associated with abnormal angiogenesis. In addition, the invention provides VEGF peptides conjugated to antibodies alone and in conjunction with other anti-angiogenic molecules.

Abstract: The present invention provides methods of treating (including preventing) a disease or condition associated with abnormal angiogenesis in a subject include administering a therapeutically effective amount of an AA targeting compound of the invention to the subject. The AA targeting compounds comprise AA targeting agent-linker conjugates which are linked to a combining site of an antibody.

Abstract: The present invention provides various uses of VEGF binding peptides, including methods to treat disorders associated with abnormal angiogenesis.