30results about How to "Increase and decrease frequency" patented technology

The present invention concerns improved methods and compositions for preparing SN-38 conjugates of proteins or peptides, preferably immunoconjugates of antibodies or antigen-binding antibody fragments. More preferably, the SN-38 is attached to the antibody or antibody fragment using a CL2A linker, with 1-12, more preferably 6 or less, most preferably 1-5 SN-38 moieties per antibody or antibody fragment. Most preferably, the immunoconjugate is prepared in large scale batches, with various modifications to the reaction scheme to optimize yield and recovery in large scale. Other embodiments concern optimized dosages and / or schedules of administration of immunoconjugate to maximize efficacy for disease treatment and minimize side effects of administration.

The present invention relates to therapeutic immunoconjugates comprising SN-38 attached to an antibody or antigen-binding antibody fragment. The antibody may bind to EGP-1 ROP-2), CEACAM5, CEACAM6, CD74, CD19, CD20, CD22, CSAp, HLA-DR, AFP or MUC5ac and the immunoconjugate may be administered at a dosage of between 4 mg / kg and 24 mg / kg, preferably 4, 6, 8, 9, 10, 12, 16 or 18 mg / kg. When administered at specified dosages and schedules, the immunoconjugate can reduce solid tumors in size, reduce or eliminate metastases and is effective to treat cancers resistant to standard therapies, such as radiation therapy, chemotherapy or immunotherapy.

The present invention relates to therapeutic immunoconjugates comprising SN-38 attached to an antibody or antigen-binding antibody fragment. The antibody may bind to EGP-1 (TROP-2), CEACAM5, CEACAM6, CD74, CD19, CD20, CD22, CSAp, HLA-DR, AFP or MUC5ac and the immunoconjugate may be administered at a dosage of between 4 mg / kg and 24 mg / kg, preferably 4, 6, 8, 9, 10, 12, 16 or 18 mg / kg. When administered at specified dosages and schedules, the immunoconjugate can reduce solid tumors in size, reduce or eliminate metastases and is effective to treat cancers resistant to standard therapies, such as radiation therapy, chemotherapy or immunotherapy.

The present invention relates to combination therapy with drugs, such as microtubule inhibitors, PARP inhibitors, Bruton kinase inhibitors or PI3K inhibitors, with antibodies or immunoconjugates against HLA-DR or Trop-2. Where immunoconjugates are used, they preferably incorporate SN-38 or pro-2PDOX. The immunoconjugate may be administered at a dosage of between 1 mg / kg and 18 mg / kg, preferably 4, 6, 8, 9, 10, 12, 16 or 18 mg / kg, more preferably 8 or 10 mg / kg. The combination therapy can reduce solid tumors in size, reduce or eliminate metastases and is effective to treat cancers resistant to standard therapies, such as radiation therapy, chemotherapy or immunotherapy. Preferably, the combination therapy has an additive effect on inhibiting tumor growth. Most preferably, the combination therapy has a synergistic effect on inhibiting tumor growth.

A method for adaptive driver guidance for navigation and location-based services. A navigation system onboard a vehicle records errors, including both system errors and user errors, where the errors can be detected by missed turns, re-routing, and similar events. The error data is transmitted to a central server, where the data is analyzed to determine patterns of errors, both for an individual driver and across many drivers. Roadway locations which frequently experience driver navigational errors have the error type integrated as a route feature, and future navigational guidance is adapted to improve driver performance. Adaptations can include increased or decreased frequency, detail, timing and location of navigational instructions. Individual driver guidance can also be adapted based on the driver's tendency to make errors in response to specific guidance instructions. Adaptation of guidance for location-based services is also provided.

The present invention relates to combination therapy with drugs, such as microtubule inhibitors, PARP inhibitors, Bruton kinase inhibitors or PI3K inhibitors, with antibodies or immunoconjugates against HLA-DR or Trop-2. Where immunoconjugates are used, they preferably incorporate SN-38 or pro-2PDOX. The immunoconjugate may be administered at a dosage of between 1 mg / kg and 18 mg / kg, preferably 4, 6, 8, 9, 10, 12, 16 or 18 mg / kg, more preferably 8 or 10 mg / kg. The combination therapy can reduce solid tumors in size, reduce or eliminate metastases and is effective to treat cancers resistant to standard therapies, such as radiation therapy, chemotherapy or immunotherapy. Preferably, the combination therapy has an additive effect on inhibiting tumor growth. Most preferably, the combination therapy has a synergistic effect on inhibiting tumor growth.

The present invention relates to biomarkers of use in cancer therapy, wherein the therapy comprises treatment with anti-Trop-2, anti-CEACAM5 or anti-HLA-DR ADCs (antibody-drug conjugates), alone or in combination with and one or more anti-cancer agents, such as a DDR inhibitor, an ABCG2 inhibitor, a microtubule inhibitor, a checkpoint inhibitor, a PI3K inhibitor, an AKT inhibitor, a CDK 4 inhibitor, a CDK 5 inhibior, a tyrosine kinase inhibitor or a platinum-based chemotherapeutic agent. Preferably, the combination therapy has a synergistic effect on inhibiting tumor growth. The biomarkers are of use to predict efficacy and / or toxicity of ADC therapy, determine tumor response to treatment, identify minimal residual disease or relapse, determine prognosis, stratify patients for initial therapy or to optimize treatment for the patient, based on the specific biomarkers detected.

The present invention relates to therapeutic ADCs comprising SN-38 attached to an anti-Trop-2 antibody or antigen-binding antibody fragment, more particularly sacituzumab govitecan. The ADC is administered to a subject with a Trop-2 positive cancer that is resistant to or relapsed from prior treatment with a checkpoint inhibitor. The therapy is effective to treat cancers that are resistant to checkpoint inhibitors.

The present invention relates to treatment of SCLC with therapeutic ADCs comprising a drug attached to an anti-Trop-2 antibody or antigen-binding antibody fragment. Preferably, the drug is SN-38. More preferably, the antibody is an hRS7 antibody and the ADC is sacituzumab govitecan. The ADC may be administered at a dosage of between 4 mg / kg and 16 mg / kg, preferably 4, 6, 8, 9, 10, 12, or 16 mg / kg, mostly preferably 8 to 10 mg / kg. When administered at specified dosages and schedules, the ADC can reduce solid tumors in size, reduce or eliminate metastases and is effective to treat cancers resistant to standard therapies, such as radiation therapy, chemotherapy or immunotherapy. Surprisingly, the ADC is effective to treat cancers that are refractory to or relapsed from irinotecan or topotecan. Preferably, the ADC is administered as a combination therapy with one or more other anti-cancer treatments, such as carboplatin or cisplatinum.

The invention describes a switching power supply system for automatically regulating an operating frequency and the method. The switching power supply system has a sensing and monitoring unit connected to the computer system for detecting the operating status of the computer system and outputting a detection value, a setting unit for setting a trigger condition value, a storage unit connected to the setting unit for storing the trigger condition value, a comparator unit connected to the storage unit and the sensing and monitoring unit for comparing the detection value with the trigger condition value and outputting a comparison result signal, and a PWM switching frequency regulator unit connected to the comparator unit and the converter for receiving the comparison result signal and regulating the operating frequency of the pulse width modulation so that a converter can supply power to the computer system more efficiently.

The invention describes a switching power supply system for automatically regulating an operating frequency and the method. The switching power supply system has a sensing and monitoring unit connected to the computer system for detecting the operating status of the computer system and outputting a detection value, a setting unit for setting a trigger condition value, a storage unit connected to the setting unit for storing the trigger condition value, a comparator unit connected to the storage unit and the sensing and monitoring unit for comparing the detection value with the trigger condition value and outputting a comparison result signal, and a PWM switching frequency regulator unit connected to the comparator unit and the converter for receiving the comparison result signal and regulating the operating frequency of the pulse width modulation so that a converter can supply power to the computer system more efficiently.

The present invention concerns improved methods and compositions for preparing SN-38 conjugates of proteins or peptides, preferably immunoconjugates of antibodies or antigen-binding antibody fragments. More preferably, the SN-38 is attached to the antibody or antibody fragment using a CL2A linker, with 1-12, more preferably 6 or less, most preferably 1-5 SN-38 moieties per antibody or antibody fragment. Most preferably, the immunoconjugate is prepared in large scale batches, with various modifications to the reaction scheme to optimize yield and recovery in large scale. Other embodiments concern optimized dosages and / or schedules of administration of immunoconjugate to maximize efficacy for disease treatment and minimize side effects of administration.

The present invention relates to therapeutic ADCs comprising SN-38 attached to an anti-Trop-2 antibody or antigen-binding antibody fragment. The ADC may be administered at a dosage of between 4 mg / kg and 18 mg / kg, preferably 4, 6, 8, 9, 10, 12, 16 or 18 mg / kg, most preferably 8 to 10 mg / kg. When administered at specified dosages and schedules, the ADC can reduce solid tumors in size, reduce or eliminate metastases and is effective to treat cancers resistant to standard therapies, such as radiation therapy, chemotherapy or immunotherapy. Preferably, the ADC is administered in combination with one or more other therapeutic agents, such as a PARP inhibitor, a microtubule inhibitor, a Bruton kinase inhibitor or a PI3K inhibitor. Most preferably, the ADC is of use for treating a Trop-2 expressing cancer, such as metastatic urothelial cancer.

The present invention relates to methods of cancer therapy using subcutaneous administration of antibody-drug conjugates (ADCs). Preferably, the ADC comprises an antibody that binds to Trop-2, CEACAM5, CEACAM6, CD20, CD22, CD30, CD46, CD74, Her-2, folate receptor, or HLA-DR. More preferably, the drug is SN-38. Subcutaneous administration is at least as effective as intravenous administration of the same ADC. Surprisingly, subcutaneous administration can be used without inducing unmanageable adverse local toxicity at the injection site. Subcutaneous administration is advantageous in requiring less frequent administration, substantially reducing the amount of time required for intravenous administration, and reducing the levels of systemic toxicities observed with intravenous administration. When administered at specified dosages and schedules, the ADCs can reduce solid tumors in size, reduce or eliminate metastases and are effective to treat cancers resistant to standard therapies, such as radiation therapy, chemotherapy or immunotherapy.

The present invention relates to treatment of SCLC with therapeutic ADCs comprising a drug attached to an anti-Trop-2 antibody or antigen-binding antibody fragment. Preferably, the drug is SN-38. More preferably, the antibody is an hRS7 antibody and the ADC is sacituzumab govitecan. The ADC may be administered at a dosage of between 4 mg / kg and 16 mg / kg, preferably 4, 6, 8, 9, 10, 12, or 16 mg / kg, mostly preferably 8 to 10 mg / kg. When administered at specified dosages and schedules, the ADC can reduce solid tumors in size, reduce or eliminate metastases and is effective to treat cancers resistant to standard therapies, such as radiation therapy, chemotherapy or immunotherapy. Surprisingly, the ADC is effective to treat cancers that are refractory to or relapsed from irinotecan or topotecan. Preferably, the ADC is administered as a combination therapy with one or more other anti-cancer treatments, such as carboplatin or cisplatinum.

The present invention relates to therapeutic immunoconjugates comprising SN-38 attached to an anti-HLA-DR antibody or antigen-binding antibody fragment. The immunoconjugate may be administered at a dosage of between 3 mg / kg and 18 mg / kg, preferably 4, 6, 8, 9, 10, 12, 16 or 18 mg / kg, more preferably 8, 10 or 12 mg / kg. When administered at specified dosages and schedules, the immunoconjugate can reduce solid tumors in size, reduce or eliminate metastases and is effective to treat cancers resistant to standard therapies, such as radiation therapy, chemotherapy or immunotherapy. The methods and compositions are particularly useful for treating AML, ALL or multiple myeloma.

The present disclosure provides a crystal-less clock and data recovery (CDR) circuit and a frequency detection method thereof. The CDR circuit includes a clock generator and a frequency detection module. The clock generator is operable to generate a clock signal. The frequency detection module coupled to the clock generator is configured for outputting a control signal to the clock generator to increase or decrease the frequency of the clock signal according to a data signal received and a transition density.

An apparatus comprises a plurality of sampling circuits configured to receive a non-Non Return to Zero (non-NRZ) data signal; and a control circuit coupled to the plurality of sampling circuits, wherein the control circuit is configured to provide one or more control signals indicating whether to decrease or increase a frequency of a clock signal associated with the non-NRZ data signal based on the non-NRZ data signal.

The present invention relates to combination therapy with drugs, such as microtubule inhibitors, PARP inhibitors, Bruton kinase inhibitors or PI3K inhibitors, with antibodies or immunoconjugates against HLA-DR or Trop-2. Where immunoconjugates are used, they preferably incorporate SN-38 or pro-2PDOX. The immunoconjugate may be administered at a dosage of between 1 mg / kg and 18 mg / kg, preferably 4, 6, 8, 9, 10, 12, 16 or 18 mg / kg, more preferably 8 or 10 mg / kg. The combination therapy can reduce solid tumors in size, reduce or eliminate metastases and is effective to treat cancers resistant to standard therapies, such as radiation therapy, chemotherapy or immunotherapy. Preferably, the combination therapy has an additive effect on inhibiting tumor growth. Most preferably, the combination therapy has a synergistic effect on inhibiting tumor growth.

A biomolecule analyzing system (10) that provides an expeditious, accurate and reliable method for analyzing a biomolecule (150). The system (10) includes two substrates (12,28) each having an inner edge (14,30), an outer edge (16,32) and an inner surfaces (20,36) from where extends a multiplicity of cilia (22). To the inner edges (14,30) is attached an input tube (82) that is also attached to a biomolecule sample reservoir (90). To the outer edges (16,32) is attached an output tube (106) that is also attached to a sample deposit chamber (120). The tubes (82,106) include a plurality of conductive plates (98) that are applied an electrical charge that causes the biomolecule (150) to traverse through the tubes (82,106). When the biomolecule (150) passes through the cilia (22) signals are produced that are applied to a pair of image capturing devices (40,50). Each device (40,50) produces a signal that is applied to an electronic data processor from where a three-dimensional image of the biomolecule (150) is produced and viewed on a data monitoring device (70).