ANTI-CDH6 ANTIBODY DRUG CONJUGATES

The present invention relates to anti-CDH6 antibodies, antibody fragments, antibody drug conjugates, and their uses for the treatment of cancer. 1. An antibody drug conjugate of the formula{'br': None, 'sub': m', 'n, 'Ab-(L-(D))'}or a pharmaceutically acceptable salt thereof; whereinAb is an antibody or antigen binding fragment thereof that specifically binds to an epitope of human CDH6;L is a linker;D is a drug moiety;m is an integer from 1 to 8; andn is an integer from 1 to 10.2. The antibody drug conjugate of claim 1 , wherein said n is 3 or 4.3. The antibody drug conjugate of or claim 1 , wherein said antibody or antigen binding fragment thereof specifically binds the extracellular domain of CDH6 claim 1 , comprising the amino acid sequence of SEQ ID NO:4.4. The antibody drug conjugate of or claim 1 , wherein said antibody or antigen binding fragment specifically binds to an epitope of human CDH6 comprising the amino acid sequence of SEQ ID NO:534.54. The antibody drug conjugate of any of - claims 1 , wherein said antibody or antigen binding fragment thereof comprises:(i) a light chain variable region that comprises (a) a LCDR1 (CDR-Complementarity Determining Region) of SEQ ID NO:224, (b) a LCDR2 of SEQ ID NO:225, (c) a LCDR3 of SEQ ID NO:226; and a heavy chain variable region that comprises: (d) a HCDR1 of SEQ ID NO: 227, (e) a HCDR2 of SEQ ID NO: 228, and (f) a HCDR3 of SEQ ID NO:229;(ii) a light chain variable region that comprises (a) a LCDR1 (CDR-Complementarity Determining Region) of SEQ ID NO:210, (b) a LCDR2 of SEQ ID NO:211, (c) a LCDR3 of SEQ ID NO:212; and a heavy chain variable region that comprises: (d) a HCDR1 of SEQ ID NO:213, (e) a HCDR2 of SEQ ID NO: 214, and (f) a HCDR3 of SEQ ID NO:215;(iii) a light chain variable region that comprises (a) a LCDR1 (CDR-Complementarity Determining Region) of SEQ ID NO:266, (b) a LCDR2 of SEQ ID NO:267, (c) a LCDR3 of SEQ ID NO:268; and a heavy chain variable region that comprises: (d) a HCDR1 of SEQ ID NO: 269 ...

Antibody Drug Conjugates

This application discloses anti-P-cadherin antibodies, antigen binding fragments thereof, and antibody drug conjugates of said antibodies or antigen binding fragments. The invention also relates to methods of treating cancer using the antibodies, antigen binding fragments, and antibody drug conjugates. Also disclosed herein are methods of making the antibodies, antigen binding fragments, and antibody drug conjugates, and methods of using the antibodies and antigen binding fragments as diagnostic reagents. 140-. (canceled)41. A nucleic acid that encodes an antibody or antigen binding fragment thereof comprising:a. a heavy chain variable region that comprises a VH CDR1 of SEQ ID NO: 1, a VH CDR2 of SEQ ID NO: 2, and a VH CDR3 of SEQ ID NO: 3, wherein the CDR is defined in accordance with the Kabat definition; and a light chain variable region that comprises a VL CDR1 of SEQ ID NO: 11, a VL CDR2 of SEQ ID NO: 12, and a VL CDR3 of SEQ ID NO: 13, wherein the CDR is defined in accordance with the Kabat definition;b. a heavy chain variable region that comprises a VH CDR1 of SEQ ID NO: 21, a VH CDR2 of SEQ ID NO: 22, and a VH CDR3 of SEQ ID NO: 23, wherein the CDR is defined in accordance with the Kabat definition; and a light chain variable region that comprises a VL CDR1 of SEQ ID NO: 31, a VL CDR2 of SEQ ID NO: 32, and a VL CDR3 of SEQ ID NO: 33, wherein the CDR is defined in accordance with the Kabat definition;c. a heavy chain variable region that comprises a VH CDR1 of SEQ ID NO:41, a VH CDR2 of SEQ ID NO:42, and a VH CDR3 of SEQ ID NO:43, wherein the CDR is defined in accordance with the Kabat definition; and a light chain variable region that comprises a VL CDR1 of SEQ ID NO:51, a VL CDR2 of SEQ ID NO:52, and a VL CDR3 of SEQ ID NO:53, wherein the CDR is defined in accordance with the Kabat definition;d. a heavy chain variable region that comprises a VH CDR1 of SEQ ID NO:61, a VH CDR2 of SEQ ID NO:62, and a VH CDR3 of SEQ ID NO:63, wherein the CDR is defined in ...

ANTIBODY DRUG CONJUGATES

This application discloses anti-P-cadherin antibodies, antigen binding fragments thereof, and antibody drug conjugates of said antibodies or antigen binding fragments. The invention also relates to methods of treating cancer using the antibodies, antigen binding fragments, and antibody drug conjugates. Also disclosed herein are methods of making the antibodies, antigen binding fragments, and antibody drug conjugates, and methods of using the antibodies and antigen binding fragments as diagnostic reagents. 1. An antibody or antigen binding fragment thereof that binds to human P-cadherin protein at one or more residues selected from the amino acids at positions 124 , 125 , 151 , 153 , 154 , 155 , 156 , 159 , 160 , 161 , 162 , 163 , 168 , 170 , 171 , and 172 of SEQ ID NO:126.2. The antibody of claim 1 , wherein the antibody binds to human P-cadherin protein at the amino acids at positions 124 claim 1 , 125 claim 1 , 151 claim 1 , 153 claim 1 , 154 claim 1 , 155 claim 1 , 156 claim 1 , 159 claim 1 , 160 claim 1 , 161 claim 1 , 162 claim 1 , 163 claim 1 , 168 claim 1 , 170 claim 1 , 171 claim 1 , and 172 of SEQ ID NO:126.3. The antibody of claim 1 , wherein the antibody comprises a heavy chain variable region that binds to human P-cadherin at one or more amino acid residues selected from positions 124 claim 1 , 151 claim 1 , 153-156 claim 1 , and 172 of SEQ ID NO:126.4. The antibody of claim 3 , wherein the heavy chain variable region binding paratope for human P-cadherin protein comprises one or more amino acid residues selected from positions 52 claim 3 , 54 claim 3 , 56 claim 3 , 60 claim 3 , 65 claim 3 , 105 claim 3 , or 107 of SEQ ID NO:128.5. The antibody of claim 1 , wherein the antibody comprises a light chain variable region that binds to human P-cadherin at one or more amino acid residues selected from positions 124 claim 1 , 125 claim 1 , 155 claim 1 , 156 claim 1 , 159-163 claim 1 , 168 claim 1 , 170 claim 1 , and 171 of SEQ ID NO:126.6. The antibody of claim ...

ANTIBODY DRUG CONJUGATES

This application discloses anti-P-cadherin antibodies, antigen binding fragments thereof, and antibody drug conjugates of said antibodies or antigen binding fragments, particularly antibody drug conjugates comprising anti-P-cadherin antibodies conjugated to auristatin analogs. The invention also relates to methods of treating cancer using the antibody drug conjugates. Also disclosed herein are methods of making the antibodies, antigen binding fragments, and antibody drug conjugates, and methods of using the antibodies and antigen binding fragments as diagnostic reagents. 1. An antibody that binds human P-cadherin selected from any one of the following:a. An antibody or antigen binding fragment thereof comprising a heavy chain variable region that comprises a VH CDR1 of SEQ ID NO: 1, a VH CDR2 of SEQ ID NO: 2, and a VH CDR3 of SEQ ID NO: 3, wherein the CDR is defined in accordance with the Kabat definition; and a light chain variable region that comprises a VL CDR1 of SEQ ID NO: 11, a VL CDR2 of SEQ ID NO: 12, and a VL CDR3 of SEQ ID NO: 13, wherein the CDR is defined in accordance with the Kabat definition, and a modified heavy chain constant region comprising cysteine at positions 152 and 375, wherein said cysteine positions are numbered according to the EU system;b. An antibody or antigen binding fragment thereof comprising a heavy chain variable region that comprises a VH CDR1 of SEQ ID NO: 21, a VH CDR2 of SEQ ID NO: 22, and a VH CDR3 of SEQ ID NO: 23, wherein the CDR is defined in accordance with the Kabat definition; and a light chain variable region that comprises a VL CDR1 of SEQ ID NO: 31, a VL CDR2 of SEQ ID NO: 32, and a VL CDR3 of SEQ ID NO: 33, wherein the CDR is defined in accordance with the Kabat definition, and a modified heavy chain constant region comprising cysteine at positions 152 and 375, wherein said cysteine positions are numbered according to the EU system;c. An antibody or antigen binding fragment thereof comprising a heavy chain variable ...

ANTI-CDH6 ANTIBODY DRUG CONJUGATES

The present invention relates to anti-CDH6 antibodies, antibody fragments, antibody drug conjugates, and their uses for the treatment of cancer. 1. An antibody drug conjugate of the formula{'br': None, 'sub': m', 'n, 'Ab-(L-(D))'}or a pharmaceutically acceptable salt thereof; whereinAb is an antibody or antigen binding fragment thereof that specifically binds to an epitope of human CDH6;L is a linker;D is a drug moiety;m is an integer from 1 to 8; andn is an integer from 1 to 10.2. The antibody drug conjugate of claim 1 , wherein said n is 3 or 4.3. The antibody drug conjugate of or claim 1 , wherein said antibody or antigen binding fragment thereof specifically binds the extracellular domain of CDH6 claim 1 , comprising the amino acid sequence of SEQ ID NO:4.4. The antibody drug conjugate of or claim 1 , wherein said antibody or antigen binding fragment specifically binds to an epitope of human CDH6 comprising the amino acid sequence of SEQ ID NO:534.5. The antibody drug conjugate of any of - claim 1 , wherein said antibody or antigen binding fragment thereof comprises:(i) a light chain variable region that comprises (a) a LCDR1 (CDR-Complementarity Determining Region) of SEQ ID NO:224, (b) a LCDR2 of SEQ ID NO:225, (c) a LCDR3 of SEQ ID NO:226; and a heavy chain variable region that comprises: (d) a HCDR1 of SEQ ID NO: 227, (e) a HCDR2 of SEQ ID NO: 228, and (f) a HCDR3 of SEQ ID NO:229;(ii) a light chain variable region that comprises (a) a LCDR1 (CDR-Complementarity Determining Region) of SEQ ID NO:210, (b) a LCDR2 of SEQ ID NO:211, (c) a LCDR3 of SEQ ID NO:212; and a heavy chain variable region that comprises: (d) a HCDR1 of SEQ ID NO:213, (e) a HCDR2 of SEQ ID NO: 214, and (f) a HCDR3 of SEQ ID NO:215;(iii) a light chain variable region that comprises (a) a LCDR1 (CDR-Complementarity Determining Region) of SEQ ID NO:266, (b) a LCDR2 of SEQ ID NO:267, (c) a LCDR3 of SEQ ID NO:268; and a heavy chain variable region that comprises: (d) a HCDR1 of SEQ ID NO: 269, ...

Fluid actuated timing mechanism

A timing mechanism actuated by hydraulic fluid uses a means responsive to vacuum to relatively displace a drive member and a driven member. When incorporated in an internal combustion engine for advancing or retarding an engine camshaft with respect to an engine crankshaft, the relative displacement is selectively controlled to reduce smog-producing exhaust emission and improve engine performance and fuel economy. In the preferred embodiment, the drive member and driven member form a fluid pressure chamber therebetween and the vacuum responsive means regulates the hydraluic fluid in said chamber. A vacuum control means which is responsive to engine operating conditions governs the application of vacuum to the vacuum responsive means. When engine operating conditions are at certain specified levels, a signal is transmitted to actuate the vacuum control means to allow the application of vacuum to the vacuum responsive means. With the application of sufficient vacuum, the vacuum responsive means allows hydraulic fluid into the chamber whereby the drive member and driven member are relatively displaced.

HEBRID COPOLIMERS AND IONIC EXCHANGE RESINS

Process for reducing thickened ends in the stretch reduction rolling of tubes

Payment management

A method and system (50) for effecting a payment from a payor in response to a payment request (52), comprising selecting a payment method from a set of payment methods (56). The payment method may be independent of a payment method selected for a payee (58). The payment may be effected by transmitting a message comprising a get funds trigger, a get funds type, a send funds trigger, and a send funds type, corresponding to the payment transaction. A method and system may receive a plurality of payment transaction notices, calculating a net account status value based on the plurality of transaction notice (60), and executing payment (62) of the net account status value.

Suspension polymerization of uniform polymer beads

UNIFORM POLYMER BEADS ARE PRODUCED BY A SUSPENSION POLYMERIZATION TECHNIQUE WITH THE AID OF A CATIONIC DISPERSING OR SUSPENDING AGENT IN COMBINATION WITH A PROTECTIVE COLLOID, THE POLYMERIZATION BEING CARRIED OUT WITH A BASIC PH. POLYMER OR COPOLYMER BEADS WHICH ARE UNIFORMLY SIZED AND WHICH REPRESENTS A RELATIVELY NARROW "CUT" OR RANGE OF A STANDARD SIEVE CLASSIFICATION ARE PRODUCED.

Remote visual inspection system

ABSTRACT A system for the remote visual inspection of a structure including two vessels, one disposed within the other and defining an annulus therebetween. A guide member is provided circumferentially about an upper periphery of the two vessels. Mounted on the guide member are two motor-driven, diametrically opposed trolleys which support a flexible track member which extends downwardly through the annulus from one of the trolleys and back up the other side of the annulus to the other trolley. At least one motor-driven carriage is mounted on the track member and carries a camera and light source. By appropriate positioning of the trolleys and the carriage, all the surfaces of the vessels defining the annulus are accessible for visual inspection by the camera. In accordance with a particular preferred embodiment, markers are placed at preselected points in the annulus on one of the vessels to permit verification of the location of the camera and carriage. Advantageously, the markers are in the form of a preselected pattern to provide verification of the clarity of the image being transmitted by the camera. In accordance with another preferred embodiment, the system further includes means for recording signals received from the camera and simultaneously recording the position of the camera.

Paint binders and their use

Desalination process

PROCESS FOR DESALINIZING LIQUIDS CONTAINING METAL SALTS

Breech of an automatic cannon

A wheel 3, which is driven intermittently transversely with respect to the weapon barrel axis 5, about an axis 4 arranged parallel to the weapon barrel axis 5, as a breech carrier of an automatic cannon, contains, in order to achieve a long operational readiness, at least one breech 1 which can be driven in a rotationally moving manner automatically about its axis 46, is axially displaceable and mechanically seals a loading space at the end of the barrel. The breech 1 is connected in a positively-locking manner to a gearing system 10, which is supported in a rotationally moving manner with respect thereto centrally in the wheel 3 and, in common with a drive element 9 of a breech carrier drive 2, has flexible transmission means 8 looped around it in a positively-locking manner. The position of the sections 35 of the elastic transmission means 8, which sections 35 are located between the drive element 9 and the gearing system 10, can be varied by means of a displacement mechanism 11, which can be controlled in a reciprocating manner transversely with respect to the weapon barrel axis 5, in such a manner that, when a breech carrier drive 2 is stationary, the gearing system 10 can be rotated clockwise or anticlockwise, and the breech 1 can be pressed against a sealing surface on the loading space, for sealing. The drive element 9 is firmly connected to a further drive element 6 which can be driven in a positively-locking manner via an intermediate gear wheel 30 of a wheel 3, as a result of which the munition feed can be guided through during the rotational movement of the wheel 3, which is constructed with windows 23, and a closing movement of the breech 1 can be prevented. <IMAGE>

Metal hydride storage

Die Erfindung betrifft einen Druckgasbehälter für den Einsatz in der Wasserstofftechnologie zur Gasspeicherung auf der Basis einer Gas/Feststoffreaktion, bestehend aus einem rohrförmigen mit Speichermasse verfüllten Einzelbehälter oder aus einem Bündel zusammengefaßter Einzelbehälter, einer Gaszuführung, einem Be- bzw. Entgasungsrohr und einem Gassammler. Bisher bekannte Druckgasbehälter mußten, damit eine einwandfreie Be- und Entlademöglichkeit bestand, mit verhältnismäßig geringen Volumen gefertigt werden und es ist die Aufgabe der Erfindung, den Druckgasbehälter so auszugestalten, daß er sowohl ein hohes spezifisches Fassungsvermögen, ein geringes Gewicht, eine schnelle und hochwirksame Be- und Entladung sowie eine hohe Lebensdauer aufweist. Gemäß der Erfindung wird daher vorgeschlagen, daß in dem Einzelbehälter zur Behälterachse radial gerichtete Schottbleche angeordnet sind, die einen zylindrischen Außensteg aufweisen und unter Vorspannung gegen die Innenwandung des Behälters dicht abschließen und daß die Schottbleche Innenstege aufweisen, mit denen sie ein zentrales Gasrohr dicht umschließen. The invention relates to a pressurized gas container for use in hydrogen technology for gas storage based on a gas / solid reaction, consisting of a tubular individual container filled with storage mass or a bundle of individual containers, a gas supply, a gas or degassing pipe and a gas collector. Previously known pressurized gas containers had to be manufactured with a relatively small volume so that there was flawless loading and unloading and it is the object of the invention to design the pressurized gas container so that it has both a high specific capacity, a low weight, a fast and highly effective loading - and discharge and has a long service life. According to the invention, it is therefore proposed that in the individual container to the container axis radially directed bulkheads are arranged, which have a cylindrical outer web and tightly close under bias ...

Payment management

A method and system (2) of effecting a payor (4) in response to a payment request, comprising selecting a payment method selected for a payee (6). The payment may be effected by transmitting a message comprising a get funds trigger, a get funds type, a send funds trigger, and a send funds type, corresponding to the payment transaction. A method and system may receive a plurality of payment transaction notices, calculating a net account status value based on the plurality of transaction notice, and executing payment of the net account status value.

Continuous casting device

Gasstauraum zwischen einer treibgasabzweigung und einem zylinder mit einem arbeitskolben zum antrieb fuer eine vorrichtung, vorzugsweise an einer automatischen rohrwaffe

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Verfahren und vorrichtung zur herstellung geschmiedeter absperrschieber

Succinatos poli-olefinicos