Chimeric Immunogenic Polypeptides

Chimeric polypeptide constructs containing multiple Ehrlichia epitopes are provided. The chimeric molecules may be synthetic or recombinant polypeptides which may be used, e.g., for diagnostic or vaccination purposes.

Patent # US11780892, US11046734, US12552843

Application Number # PCT/US19/43840, AU2019311181, BR112021001420-9, CA3107319, EP19842185.1, CN201980059990.7, US19/532418

EHRLICHIA IMMUNODOMINANT PROTEINS

Antigenic proteins of Ehrlichia are identified, including newly identified immunodominant proteins. Such proteins can be used to diagnose ehrlichiosis or vaccinate against Ehrlichia. The identification of the immunodominant proteins was performed based on extensive analysis of proteins expressed by Ehrlichia.

Application Number # PCT/US24/60651

Ehrlichia Immunoreactive GP47 And GP36 Antigens For Diagnosis And Vaccination

Immunoreactive gp47 and gp36 proteins in Ehrlichia chaffeensis and E. canis are provided. These proteins may be used for diagnosis of Ehrlichiosis in humans and/or dogs. The proteins may also be included in vaccine compositions against Ehrlichia infection.

Patent # US9140702, US9645148, RE46254, MX296016, CA2612302, BR PI0611820-8

Application Number # US11/917390

IMMUNODOMINANT PEPTIDES

Synthetic immunoreactive peptides are provided and can be used to diagnose or vaccinate against Ehrlichia canis and/or Ehrlichia chaffeensis.

Patent # US 12,226,468

Application Number # PCT/US24/35561, US19/040,374

Immunoreactive Ehrlichia P120 / P140 Epitopes And Uses Thereof

Provided are peptides which can selectively bind Ehrlichia-specific anti-p 120 or anti-p 140 antibodies. Methods and kits utilizing the immunoreactive peptides are also provided. The immunoreactive peptides may be utilized, e.g., for determining whether or not a subject is infected with Ehrlichia chaffeensis or Ehrlichia canis. In certain embodiments, the immunoreactive peptides may be utilized in an ELISA or lateral flow assay

Patent # US8329189, CA2796563, EP2424880

Application Number # PCT/US2010/032744

Immunoreactive Ferric Binding Protein Of Ehrlichia

An immunoreactive ferric binding protein (Fbp) (38-kDa) protein of Ehrlichia canis. This protein may be used in vaccine compositions to immunize animals against E. canis.

Patent # US7722880, CA2555413

Application Number # 11/066648

P153 And P156 Antigens Of Ehrlichia Bacteria

Sequences encoding two immunoreactive glycoproteins from Ehrlichia canis and Ehrlichia chaffeensis. These two glycoproteins are species-specific and immunoreactive and may be used for subunit vaccines and for serologic and molecular diagnostics for E. canis and E. chaffeensis.

Patent # US7204992, US7754224, EP1581638, JP4494974, MX257637, CN200380108238.6, CN200810087960.0

PROTEINS FOR EHRLICHIA DIAGNOSIS AND VACCINATION

Antigenic Ehrlichia proteins are provided. The antigenicity of these proteins was compared with TRP47, and select exhibit antigenicity greater than TRP47. The proteins may be included in a diagnostic test for ehrlichiosis or in a vaccine composition.

Application Number # PCT/US21/31509

Vaccines Comprising Immunoreactive Glycoprotein Gp19 Of Ehrlichia Canis

Vaccines compsising a highly conserved 19 kDa major immunoreactive glycoprotein (gp19) in E. canis, the ortholog of the E. chaffeensis VLPT, are provided. The E. canis gp19 lacks tandem repeats present in VLPT of E. chaffeensis, but the two proteins exhibit substantial amino acid similarity, and both genes have the same relative chromosomal location. Vaccine compositions may be used to protect against ehrlichiosis.

Patent # US9814768, US9605032, US9605033, EP2064231, JP5498164, JP5837917, CA2662246, AU2007348944

Application Number # PCT/US2007/075343

Vaccines For The Ehrlichioses Comprising GP19 Or VLPT Antigens

Vaccine compositions comprising gp19 of E. canis and TR6 containing ortholog (VLPT) in E. chaffeensis are provided. Synthetic and/or recombinant polypeptides corresponding to various regions of VLPT were used to localize major antibody epitopes to the TR-containing region. Major antibody epitopes were identified. The vaccine compositions may be used to protect against Ehrlichiosis.

Patent # US10131705, US9850295, US9605036, US9605035, EP2245049, KR1588736, MX314676, JP5677703, BR-PI0906429-0, CA2711499

Application Number # PCT/US09/030527

Biologic Drug for the Treatment of Cancer and Disease

Cell-targeted cytotoxic compounds are provided, including cymirafen. Such compounds can be used, e.g., to selectively bind and kill cancer cells such as cancer stem cells that express LGR4, LGR5, or LGR6. In some embodiments, the cytotoxic compounds include an LGR binding polypeptide, a cytotoxic agent (e.g., MMAE), and an Fc region (e.g., a mutant Fc domain). Methods for using the compounds to treat cell proliferative diseases such as cancers are also provided.

Application Number # PCT/US23/77748

Granzyme Molecules And Therapies

Cell-targeted serine protease constructs are provided. Such constructs can be used in methods for targeted cell killing such as for treatment cell of proliferative diseases (e.g., cancer). In some aspects, recombinant serine proteases, such as Granzyme B polypeptides, are provided that exhibit improved stability and cell toxicity. Methods and compositions for treating lapatinib or trastuzumab-resistant cancers are also provided.

Patent # US11535838, US10323239, US9096840, US9499807, US9951325, US10738295, US10920211, EP2904004, EP3456734, CA2885376, AU2013326933, AU2017228534, JP6306596, JP6722134, JP7403521

Application Number # PCT/US13/063402

Leader Peptides For Secreting Recombinant Proteins

Leader peptides that mediate enhanced export of heterologous proteins from bacteria. Such peptides may be useful in recombinant protein expression. Methods for identifying such leader peptides are also described

Patent # US7419783

RSPO1-targeting Therapies

RSPO1-targeting therapies are provided. In some embodiments, a R-spondin 1 (RSPO1)-targeting ligand is used to deliver a cytotoxic moiety (e.g., MMAE) to a cancerous cell.

Patent # US11913043, US11193117, CA3014921, EP3417058,

Application Number # PCT/US17/18116, US18/425681

Therapeutic Agents Comprising Pro-Apoptotic Proteins

Chimeric polypeptides with cell targeting moieties and signal transduction factors. For example fusion proteins between antibody targeting molecules and apoptosis inducing factors, such as granzyme B and pro-apoptotic Bcl-2 family members. These chimeric molecules may be used in the treatment of cell proiferative diseases such as cancer.

Patent # US7101977, US7371723, US7759091, US8043831, US8530225, EP1414471, AU2002327310, ZA20040228, RU2319709, KR0891272, NZ530582, IL159894, CN02817979, CA2454048

Application Number # PCT/US2002/004195

APPARATUS AND METHODS FOR INTRA-VASCULAR LASER LITHOTRIPSY

Provided are apparatus and methods for the fracture of arterial calcifications. The apparatus can include (1) use of plastic catheters, which provide an advantage in that they are easier to process and to combine with optical elements, (2) a catheter design with a guide wire and an overlying balloon, (3) optical elements on plastic wires to focus the light into an absorbing fluid (e.g., ICG), and (4) approach that can allow multiple shock waves using a single fiber and laser system. Multiple shock-wave emitters can be included in a single fiber, and a laser system can be configured in real time to emit shock waves from any arbitrary combination of the emitters, allowing laser output to be controlled based on the size of a calcium deposit.

Application Number # PCT/US24/10920, US18/408284, EP24741904.7, AU2024207835, JP2025-540176, KR10-2025-7024693

Biologic Drug for the Treatment of Cancer and Disease

Cell-targeted cytotoxic compounds are provided, including cymirafen. Such compounds can be used, e.g., to selectively bind and kill cancer cells such as cancer stem cells that express LGR4, LGR5, or LGR6. In some embodiments, the cytotoxic compounds include an LGR binding polypeptide, a cytotoxic agent (e.g., MMAE), and an Fc region (e.g., a mutant Fc domain). Methods for using the compounds to treat cell proliferative diseases such as cancers are also provided.

Application Number # PCT/US23/77748

Granzyme Molecules And Therapies

Cell-targeted serine protease constructs are provided. Such constructs can be used in methods for targeted cell killing such as for treatment cell of proliferative diseases (e.g., cancer). In some aspects, recombinant serine proteases, such as Granzyme B polypeptides, are provided that exhibit improved stability and cell toxicity. Methods and compositions for treating lapatinib or trastuzumab-resistant cancers are also provided.

Patent # US11535838, US10323239, US9096840, US9499807, US9951325, US10738295, US10920211, EP2904004, EP3456734, CA2885376, AU2013326933, AU2017228534, JP6306596, JP6722134, JP7403521

Application Number # PCT/US13/063402

Methods For Predicting Kinase Inhibitor Resistance

YESS (yeast endoplasmic reticulum sequestration screening) methods are provided to predict if a particular kinase inhibitor (e.g., to treat a cancer) will be more or less susceptible to the emergence of resistance mutations during clinical use in vivo that may decrease the effectiveness of the kinase inhibitor. In some aspects, the YESS methodology is used to evolve kinases in the presence of kinase inhibitors. The mutations observed in the mutant kinases evolved in vitro have also been observed in cancers in vivo.

Patent # US16/178991

Application Number # PCT/US18/58834, US16/178991, AU2018358144, CA3079985, EP18874197.9

METHODS OF MICROBIOME CHARACTERIZATION AND MONITORING

Methods of microbiome characterization and monitoring using subspecies analysis by machine learning or artificial intelligence approaches are provided.

Application Number # PCT/US25/42133

RSPO1-targeting Therapies

RSPO1-targeting therapies are provided. In some embodiments, a R-spondin 1 (RSPO1)-targeting ligand is used to deliver a cytotoxic moiety (e.g., MMAE) to a cancerous cell.

Patent # US11913043, US11193117, CA3014921, EP3417058,

Application Number # PCT/US17/18116, US18/425681

Steap2 Inhibitors For The Treatment Of Liver Cancers

Six Transmembrane Epithelial Antigen of Prostate 2 (STEAP2) is overexpressed in Hispanics and may contribute to hepatocellular carcinoma (HCC). Methods of targeting STEAP2 to treat HCC, such as via siRNA or shRNA, are provided.

Patent # US11168327

Application Number # PCT/US18/16212

Therapeutic Agents Comprising Pro-Apoptotic Proteins

Chimeric polypeptides with cell targeting moieties and signal transduction factors. For example fusion proteins between antibody targeting molecules and apoptosis inducing factors, such as granzyme B and pro-apoptotic Bcl-2 family members. These chimeric molecules may be used in the treatment of cell proiferative diseases such as cancer.

Patent # US7101977, US7371723, US7759091, US8043831, US8530225, EP1414471, AU2002327310, ZA20040228, RU2319709, KR0891272, NZ530582, IL159894, CN02817979, CA2454048

Application Number # PCT/US2002/004195

Recombinant Filaggrin Polypeptides For Cell Importation

Methods and compositions for the intracellular transport of liposomal filaggrin for treatment of skin disease are provided.

Patent # US10336797

Application Number # US13/511,267

Automated Coronary Plaque Characterization And Risk Assessment Using Virtual Histology IVOCT

Provided are methods and systems to classify plaque tissue present in the coronary artery using intravascular optical coherence tomography (IVOCT) images co-registered with histology for validation. Our virtual histology technology allows for much quicker and more accurate reading of IVOCT images. Market research indicates that implementing virtual histology (VH) leads to a better and broader uptake of diagnostic technologies since the burden or interpretation of the images and data is greatly reduced. For example, Volcano used VH-IVUS to outcompete Boston Scientific in the IVUS market — Volcano had 92% compared to Boston Scientific's 8% market share by 2015.

Patent # US 12,213,810

Application Number # PCT/US17/36587

Chimeric Immunogenic Polypeptides

Chimeric polypeptide constructs containing multiple Ehrlichia epitopes are provided. The chimeric molecules may be synthetic or recombinant polypeptides which may be used, e.g., for diagnostic or vaccination purposes.

Patent # US11780892, US11046734, US12552843

Application Number # PCT/US19/43840, AU2019311181, BR112021001420-9, CA3107319, EP19842185.1, CN201980059990.7, US19/532418

EHRLICHIA IMMUNODOMINANT PROTEINS

Antigenic proteins of Ehrlichia are identified, including newly identified immunodominant proteins. Such proteins can be used to diagnose ehrlichiosis or vaccinate against Ehrlichia. The identification of the immunodominant proteins was performed based on extensive analysis of proteins expressed by Ehrlichia.

Application Number # PCT/US24/60651

IMMUNODOMINANT PEPTIDES

Synthetic immunoreactive peptides are provided and can be used to diagnose or vaccinate against Ehrlichia canis and/or Ehrlichia chaffeensis.

Patent # US 12,226,468

Application Number # PCT/US24/35561, US19/040,374

Immunoreactive Ehrlichia P120 / P140 Epitopes And Uses Thereof

Provided are peptides which can selectively bind Ehrlichia-specific anti-p 120 or anti-p 140 antibodies. Methods and kits utilizing the immunoreactive peptides are also provided. The immunoreactive peptides may be utilized, e.g., for determining whether or not a subject is infected with Ehrlichia chaffeensis or Ehrlichia canis. In certain embodiments, the immunoreactive peptides may be utilized in an ELISA or lateral flow assay

Patent # US8329189, CA2796563, EP2424880

Application Number # PCT/US2010/032744

Immunoreactive Polypeptides

Antigenic Ehrlichia proteins are provided. Ehrlichia proteins that exhibit antigenicity greater than TRP47 are provided and can be used for diagnosis of Ehrlichia and/or included in a vaccine composition.

Patent # US12461099, AU2019267569, MX430947

Application Number # PCT/US19/31137

Methods For Predicting Kinase Inhibitor Resistance

YESS (yeast endoplasmic reticulum sequestration screening) methods are provided to predict if a particular kinase inhibitor (e.g., to treat a cancer) will be more or less susceptible to the emergence of resistance mutations during clinical use in vivo that may decrease the effectiveness of the kinase inhibitor. In some aspects, the YESS methodology is used to evolve kinases in the presence of kinase inhibitors. The mutations observed in the mutant kinases evolved in vitro have also been observed in cancers in vivo.

Patent # US16/178991

Application Number # PCT/US18/58834, US16/178991, AU2018358144, CA3079985, EP18874197.9

METHODS OF MICROBIOME CHARACTERIZATION AND MONITORING

Methods of microbiome characterization and monitoring using subspecies analysis by machine learning or artificial intelligence approaches are provided.

Application Number # PCT/US25/42133

Multi-Channel Orthogonal Confolutional Neural Networks

Provided are an apparatus and related methods to classify a plaque tissue present in the coronary artery using intravascular optical coherence tomography (IVOCT) images. The methods may use neural networks to analyze and classify elements from the imaging data provided.

Patent # US11779220

Application Number # PCT/US19/65850

NEURAL NETWORK SYSTEMS FOR smORF PEPTIDES

Shortstop methods and software are provided for identifying small open reading frame (smORF) peptides that may be excreted and/or have biological function.

Application Number # PCT/US24/59319, US18/975313

PROTEINS FOR EHRLICHIA DIAGNOSIS AND VACCINATION

Antigenic Ehrlichia proteins are provided. The antigenicity of these proteins was compared with TRP47, and select exhibit antigenicity greater than TRP47. The proteins may be included in a diagnostic test for ehrlichiosis or in a vaccine composition.

Application Number # PCT/US21/31509

Systems And Methods For Coronary Occlusion Treatment

SmartLaser Wire technology to treat occlusions, including coronary artery chronic total occlusions. •CTOs found in about 20% of patients undergoing angiography •~2 million patients undergo diagnostic angiography annually in the U.S •CTO treatment options: Medication: ~60% Bypass: ~30% PCI: ~10% •CTO PCI is a very complex procedure with failure rate of 20%. Success rates highest among centers training on advanced techniques •Of 2,632 U.S. interventional cardiologists, only 301 felt competent to perform complex CTO procedures •Most common cause of failure is inability to cross occlusion with a guidewire •Stenting is often performed in the wall of the coronary artery •Solution is to cross in the true lumen, which was not possible due to calcifications - our SmartLaser Wire can get through calcifications and thereby cross the true lumen!

Patent # US12171408, US11517374, EP3691512, AU2018346252, CA3076852

Application Number # PCT/US18/54063

Systems And Methods For Endometrial Tissues Identification

Provided are systems and methods to identify endometrial tissue. These systems can be used to detect optical properties of endometriosis to improve surgical removal. Exemplary systems and methods disclosed herein can identify endometrial tissue via the endogenous fluorescence of hemosiderin when subjected to excitation light

Patent # US12013342, US10663403, US11009465, US11506607, US18/050902, AU2018270943, BR112019023913-8, CA3063187, KR10-2621221, KR10-2019-7037195, JP7332483

Application Number # PCT/US18/32877, EP18801351.0

Systems and Methods for Ultrasound and Photoacoustic Guidance of Coronary Procedures

Apparatuses and methods for treatment of chronic total occlusion (CTO) of blood vessels (e.g., in the heart) based on and using an ICE-guided Cold Laser Wire (CLW) catheter are provided. The ICE-guided Cold Laser Wire (CLW) catheter can include: (a) a small, flexible and steerable catheter that can provide real-time ranging data, (b) laser cutting and cryogenic cooling that allows for crossing coronary CTOs more safely and without damage to the vessel wall, and (c) the calcium cutting laser allows true lumen crossing of CTOs with excessive calcification.

Application Number # PCT/US21/50147, US18/044408, AU2021340881, CA3192117, EP21867792, JP2023-516488

COMBINATION THERAPY FOR THE TREATMENT OF METABOLIC DISEASES AND DISORDERS

Alendronate in combination with inactivated P. goldsteinii can be administered to a subject to treat obesity, e.g., in postmenopausal patients.

Application Number # PCT/US24/21855, US18/619514

IMMUNODOMINANT PEPTIDES

Synthetic immunoreactive peptides are provided and can be used to diagnose or vaccinate against Ehrlichia canis and/or Ehrlichia chaffeensis.

Patent # US 12,226,468

Application Number # PCT/US24/35561, US19/040,374

Recombinant Filaggrin Polypeptides For Cell Importation

Methods and compositions for the intracellular transport of liposomal filaggrin for treatment of skin disease are provided.

Patent # US10336797

Application Number # US13/511,267

Chimeric Immunogenic Polypeptides

Chimeric polypeptide constructs containing multiple Ehrlichia epitopes are provided. The chimeric molecules may be synthetic or recombinant polypeptides which may be used, e.g., for diagnostic or vaccination purposes.

Patent # US11780892, US11046734, US12552843

Application Number # PCT/US19/43840, AU2019311181, BR112021001420-9, CA3107319, EP19842185.1, CN201980059990.7, US19/532418

Class IIA Hdac Inhibitors For The Treatment Of Infection

Macrophage class IIa HDACs are shown to link cAMP signaling to inflammation and insulin resistance. In some embodiments, a HDAC4 inhibitor may be used to treat a bacterial infection by a bacteria that evades immune destruction by increasing cAMP, such as anthrax or tubercul

Patent # US9693994

Application Number # PCT/US15/25072

EHRLICHIA IMMUNODOMINANT PROTEINS

Antigenic proteins of Ehrlichia are identified, including newly identified immunodominant proteins. Such proteins can be used to diagnose ehrlichiosis or vaccinate against Ehrlichia. The identification of the immunodominant proteins was performed based on extensive analysis of proteins expressed by Ehrlichia.

Application Number # PCT/US24/60651

IMMUNODOMINANT PEPTIDES

Synthetic immunoreactive peptides are provided and can be used to diagnose or vaccinate against Ehrlichia canis and/or Ehrlichia chaffeensis.

Patent # US 12,226,468

Application Number # PCT/US24/35561, US19/040,374

Immunoreactive Polypeptides

Antigenic Ehrlichia proteins are provided. Ehrlichia proteins that exhibit antigenicity greater than TRP47 are provided and can be used for diagnosis of Ehrlichia and/or included in a vaccine composition.

Patent # US12461099, AU2019267569, MX430947

Application Number # PCT/US19/31137

PROTEINS FOR EHRLICHIA DIAGNOSIS AND VACCINATION

Antigenic Ehrlichia proteins are provided. The antigenicity of these proteins was compared with TRP47, and select exhibit antigenicity greater than TRP47. The proteins may be included in a diagnostic test for ehrlichiosis or in a vaccine composition.

Application Number # PCT/US21/31509

Apparatus And Method For Evaluations Bright Spot Indications Observed Through Optical OCT

Apparatus and methods for identifying bright spot indications observed through optical coherence tomography. The indications can be evaluated, for example, to link risk factors or other conditions to clinically relevant outcomes.

Patent # US9633277

Application Number # PCT/US/49637

Apparatus and Methods for Phase Agnostic Stimuli

Methods and algorithms to affect electrical activity in a subject regardless of the phase window are provided.

Patent # US12458807, CA3195980

Application Number # PCT/US21/55725, EP21883753

Automated Coronary Plaque Characterization And Risk Assessment Using Virtual Histology IVOCT

Provided are methods and systems to classify plaque tissue present in the coronary artery using intravascular optical coherence tomography (IVOCT) images co-registered with histology for validation. Our virtual histology technology allows for much quicker and more accurate reading of IVOCT images. Market research indicates that implementing virtual histology (VH) leads to a better and broader uptake of diagnostic technologies since the burden or interpretation of the images and data is greatly reduced. For example, Volcano used VH-IVUS to outcompete Boston Scientific in the IVUS market — Volcano had 92% compared to Boston Scientific's 8% market share by 2015.

Patent # US 12,213,810

Application Number # PCT/US17/36587

METHODS AND APPARATUS FOR HIGH-SPEED AND HIGH-ASPECT RATIO LASER SUBTRACTIVE MATERIAL PROCESSING

Apparatus and methods for the efficient and precise ablation of tissues are provided. Certain embodiments include a first laser configured to direct a first pulse of energy at a first wavelength to a region of tissue; a second laser configured to direct a second pulse of energy at a second wavelength to the region of tissue; and a control system configured to control operation of the first laser and the second laser. The tissue can be cut by creating a bubble in the tissue and then bursting the bubble.

Patent # JP7715346, AU2020274050

Application Number # PCT/US20/32443, US17/611315, CA3139128, EP20805732

Multi-Channel Orthogonal Confolutional Neural Networks

Provided are an apparatus and related methods to classify a plaque tissue present in the coronary artery using intravascular optical coherence tomography (IVOCT) images. The methods may use neural networks to analyze and classify elements from the imaging data provided.

Patent # US11779220

Application Number # PCT/US19/65850

OCT Image Guided Laser Knife

This image guided laser knofice is composed of a finer-based OCT device coupled with a pulsed infrared fiber laser, allowing real time imaging and surgery in previously inaccessible spaces.

Patent # US9482513, US10495440, JP7116762

Application Number # PCT/US14/28403

Systems And Methods For Coronary Occlusion Treatment

SmartLaser Wire technology to treat occlusions, including coronary artery chronic total occlusions. •CTOs found in about 20% of patients undergoing angiography •~2 million patients undergo diagnostic angiography annually in the U.S •CTO treatment options: Medication: ~60% Bypass: ~30% PCI: ~10% •CTO PCI is a very complex procedure with failure rate of 20%. Success rates highest among centers training on advanced techniques •Of 2,632 U.S. interventional cardiologists, only 301 felt competent to perform complex CTO procedures •Most common cause of failure is inability to cross occlusion with a guidewire •Stenting is often performed in the wall of the coronary artery •Solution is to cross in the true lumen, which was not possible due to calcifications - our SmartLaser Wire can get through calcifications and thereby cross the true lumen!

Patent # US12171408, US11517374, EP3691512, AU2018346252, CA3076852

Application Number # PCT/US18/54063

Systems And Methods For Endometrial Tissues Identification

Provided are systems and methods to identify endometrial tissue. These systems can be used to detect optical properties of endometriosis to improve surgical removal. Exemplary systems and methods disclosed herein can identify endometrial tissue via the endogenous fluorescence of hemosiderin when subjected to excitation light

Patent # US12013342, US10663403, US11009465, US11506607, US18/050902, AU2018270943, BR112019023913-8, CA3063187, KR10-2621221, KR10-2019-7037195, JP7332483

Application Number # PCT/US18/32877, EP18801351.0

SYSTEMS AND METHODS FOR LASER-INDUCED CALCIUM FRACTURES

Methods and apparatuses related to fracture of arterial calcifications during coronary and peripheral intervention are provided. Studies are provided showing that light can be used to generate micro-cavitations and secondary calcium fracture in ex vivo human calcified coronary arteries.

Application Number # US17/548467, AU2021397309, CA3200965, EP21904479, JP2023-535463, CN-pending, KR10-2023-7021214

Systems and Methods for Ultrasound and Photoacoustic Guidance of Coronary Procedures

Apparatuses and methods for treatment of chronic total occlusion (CTO) of blood vessels (e.g., in the heart) based on and using an ICE-guided Cold Laser Wire (CLW) catheter are provided. The ICE-guided Cold Laser Wire (CLW) catheter can include: (a) a small, flexible and steerable catheter that can provide real-time ranging data, (b) laser cutting and cryogenic cooling that allows for crossing coronary CTOs more safely and without damage to the vessel wall, and (c) the calcium cutting laser allows true lumen crossing of CTOs with excessive calcification.

Application Number # PCT/US21/50147, US18/044408, AU2021340881, CA3192117, EP21867792, JP2023-516488

APPARATUS AND METHODS FOR INTRA-VASCULAR LASER LITHOTRIPSY

Provided are apparatus and methods for the fracture of arterial calcifications. The apparatus can include (1) use of plastic catheters, which provide an advantage in that they are easier to process and to combine with optical elements, (2) a catheter design with a guide wire and an overlying balloon, (3) optical elements on plastic wires to focus the light into an absorbing fluid (e.g., ICG), and (4) approach that can allow multiple shock waves using a single fiber and laser system. Multiple shock-wave emitters can be included in a single fiber, and a laser system can be configured in real time to emit shock waves from any arbitrary combination of the emitters, allowing laser output to be controlled based on the size of a calcium deposit.

Application Number # PCT/US24/10920, US18/408284, EP24741904.7, AU2024207835, JP2025-540176, KR10-2025-7024693

Automated Coronary Plaque Characterization And Risk Assessment Using Virtual Histology IVOCT

Provided are methods and systems to classify plaque tissue present in the coronary artery using intravascular optical coherence tomography (IVOCT) images co-registered with histology for validation. Our virtual histology technology allows for much quicker and more accurate reading of IVOCT images. Market research indicates that implementing virtual histology (VH) leads to a better and broader uptake of diagnostic technologies since the burden or interpretation of the images and data is greatly reduced. For example, Volcano used VH-IVUS to outcompete Boston Scientific in the IVUS market — Volcano had 92% compared to Boston Scientific's 8% market share by 2015.

Patent # US 12,213,810

Application Number # PCT/US17/36587

COMBINATION THERAPY FOR THE TREATMENT OF METABOLIC DISEASES AND DISORDERS

Alendronate in combination with inactivated P. goldsteinii can be administered to a subject to treat obesity, e.g., in postmenopausal patients.

Application Number # PCT/US24/21855, US18/619514

Corticotropin Releasing Factor Receptor-2 Inhibitors And Uses Thereof

Methods for increasing insulin sensitivity in an individual by reducing corticotropin releasing factor receptor-2 (CRFR-2) signaling. Methods of decreasing insulin secretion in the pancreas are also described. These methods are of particular relevance in subjects who have become insulin resistant such as those with type 2 diabetes or metabolic syndrome.

Patent # US7815905

Application Number # US11/668047

Homeobox Factor Stimulating Insulin Expression

Modulation of the level of insulin in the treatment of diabetes. An isolated homeobox-type transcription factor protein is characterized by having the ability to bind to a plurality of promoters that control hormone gene expression in pancreatic islet cells, including binding to insulin and somatostatin gene promoters. Also provided is an isolated nucleic acid encoding such a transcription factor.

Patent # US5741673

Methods And Probiotic Compositions For The Treatment Of Bone Disorders

Methods of treating osteoporosis and other bone density disorders with warm microbiome bacteria are provided. Related pharmaceutical and probiotic compositions are also provided.

Patent # US11541083, AU2019351019, EP3856147

Application Number # PCT/US19/53402, US18/060,134, CA3113448

METHODS AND PROBIOTIC COMPOSITIONS FOR THE TREATMENT OF METABOLIC DISEASES AND DISORDERS

Heat inactivated or dead Parabacteroides Goldsteinii may be used to increase insulin sensitivity, and treat diseases including obesity and diabetes. Methods of culturing bacteria in spermine and spermidine and using these compounds for the treatment of metabolic diseases are also provided. Additional microbiota and related compositions and methods for treating bone diseases and/or metabolic diseases are also provided.

Patent # US11883447, JP7761556, CN202080064409, AU2020348461

Application Number # PCT/US20/51581

Methods For Treating Insulin Resistance And For Sensitzing Patients To GIP1 Agonist Therapy

Provided are methods for reversing resistance to a GLP-1 agonist (e.g., Byetta) in type 2 diabetes patients by administration of a Protein Kinase Inhibitor Beta (PKIB) pathway inhibitor. In some aspects, the PKIB pathway inhibitor is a HIF antagonist, a mTOR inhibitor (e.g., rapamycin), or an siRNA targeted to PKIB.

Patent # US10258639

METHODS OF MICROBIOME CHARACTERIZATION AND MONITORING

Methods of microbiome characterization and monitoring using subspecies analysis by machine learning or artificial intelligence approaches are provided.

Application Number # PCT/US25/42133

Multi-Channel Orthogonal Confolutional Neural Networks

Provided are an apparatus and related methods to classify a plaque tissue present in the coronary artery using intravascular optical coherence tomography (IVOCT) images. The methods may use neural networks to analyze and classify elements from the imaging data provided.

Patent # US11779220

Application Number # PCT/US19/65850

SHP2 Inhibitors And Methods Of Use Thereof

SHP2 is involved in insulin receptor (IR) internalization, and inhibition of SHP2 alleviates high-fat-diet-induced insulin resistance in mice.

Application Number # US16/261819

Soluble G-Protein Coupled Receptors

Corticotropin release factor receptor(CRFR) 2-alpha a novel CRF receptor is described. The receptor enables methods for modulating CRF signaling.

Patent # US8258279, US7507794, EP1885746, CA2597065, RU2423378, CN101137668, JP4859248

Application Number # PCT/US2006/004321

Systems And Methods For Coronary Occlusion Treatment

SmartLaser Wire technology to treat occlusions, including coronary artery chronic total occlusions. •CTOs found in about 20% of patients undergoing angiography •~2 million patients undergo diagnostic angiography annually in the U.S •CTO treatment options: Medication: ~60% Bypass: ~30% PCI: ~10% •CTO PCI is a very complex procedure with failure rate of 20%. Success rates highest among centers training on advanced techniques •Of 2,632 U.S. interventional cardiologists, only 301 felt competent to perform complex CTO procedures •Most common cause of failure is inability to cross occlusion with a guidewire •Stenting is often performed in the wall of the coronary artery •Solution is to cross in the true lumen, which was not possible due to calcifications - our SmartLaser Wire can get through calcifications and thereby cross the true lumen!

Patent # US12171408, US11517374, EP3691512, AU2018346252, CA3076852

Application Number # PCT/US18/54063

SYSTEMS AND METHODS FOR LASER-INDUCED CALCIUM FRACTURES

Methods and apparatuses related to fracture of arterial calcifications during coronary and peripheral intervention are provided. Studies are provided showing that light can be used to generate micro-cavitations and secondary calcium fracture in ex vivo human calcified coronary arteries.

Application Number # US17/548467, AU2021397309, CA3200965, EP21904479, JP2023-535463, CN-pending, KR10-2023-7021214

Systems and Methods for Ultrasound and Photoacoustic Guidance of Coronary Procedures

Apparatuses and methods for treatment of chronic total occlusion (CTO) of blood vessels (e.g., in the heart) based on and using an ICE-guided Cold Laser Wire (CLW) catheter are provided. The ICE-guided Cold Laser Wire (CLW) catheter can include: (a) a small, flexible and steerable catheter that can provide real-time ranging data, (b) laser cutting and cryogenic cooling that allows for crossing coronary CTOs more safely and without damage to the vessel wall, and (c) the calcium cutting laser allows true lumen crossing of CTOs with excessive calcification.

Application Number # PCT/US21/50147, US18/044408, AU2021340881, CA3192117, EP21867792, JP2023-516488

Treatment Of Diabetes By Co-Stimulation Of CRF-R1 And CRF-R2

Selective CRF-R1 and CRF-R2 agonists may be used in combination to promote insulin production. Methods are provided for the treatment of type I and/or treat type II diabetes.

Patent # US9314506

Application Number # PCT/US12/061593

Elimination Of Proliferating Cells From Stem Cell-Derived Grafts

Provided are methods and compositions for a suicide gene approach comprising an expression vector comprising a cell cycle-dependent promoter driving the expression of a suicide gene. Also provided herein are methods to render proliferative cells sensitive to a prodrug after transplantation but avoids expression of the suicide gene in post-mitotic cells, such as neurons.

Application Number # US16/204320

Elimination Of Proliferating Cells From Stem-Cell Derived Grafts

Stem-cell derived grafts hold great therapeutic promise but recent clinical cases have highlighted the potential dangers associated with the presence of proliferating cells in the graft. We have developed a method to specifically eliminate proliferating cells in stem cell-derived grafts of neurons and other cell-based therapies where the final target consists of post-mitotic cells.

Patent # JP7099967, AU2017290805, EP3478325

Application Number # PCT/US17/40303, CA3029582

Generation Of Dopaminergic Neurons

Methods and compositions for differentiating neuronal precursors into dopaminergic neurons are provided. Zoxazolamine is used in certain embodiments to promote or enhance dopaminergic differentiation. Also provided are neurotoxicity tests or screening methods using dopaminergic neurons generated via these methods.

Patent # US8815592

Application Number # PCT/US2011/033232

Methods for Making and Using Differentiated Neural Cells

Methods for differentiating stem and progenitor cells into neural cells through an approach that excludes the use of SMAD or Noggin inhibition are provided. Methods for differentiating stem or progenitor cells into neural cells can include contacting cells with a compound selected from DMH1, DMH2, K02288, A8301, or combinations thereof.

Application Number # PCT/US2021/054462

Stem Cell Clones With Defined Differentiation Capabilities

Methods for the selection of clones from a single stem cell line which exhibit improved differentiation properties is provided. In particular, the inventor has observed that specific subclones derived from a single embryonic stem cell line display a wide variety in their ability to differentiate into a specific cell lineage, such as dopaminergic neurons. This finding has allowed for the selection of specific subclones obtained via serial dilution which consistently exhibit improved differentiation properties.

Patent # US10947499

Application Number # US12/958,183

Transgenic Mice Deficient In Corticotropin-Releasing Factor Receptor 2 (CRFR 2)

Transgenic mice deficient in corticotropin-releasing factor receptor 2 (CRFR-2), a critical integrator of the hypothalamic-pituitary-adrenal (HPA) axis in response to stress. These mice are useful for the study of anxiety, depression, and the physiology of the HPA axis.

Patent # US7674463

Application Number # US09/714,692

Elimination Of Proliferating Cells From Stem Cell-Derived Grafts

Provided are methods and compositions for a suicide gene approach comprising an expression vector comprising a cell cycle-dependent promoter driving the expression of a suicide gene. Also provided herein are methods to render proliferative cells sensitive to a prodrug after transplantation but avoids expression of the suicide gene in post-mitotic cells, such as neurons.

Application Number # US16/204320

Elimination Of Proliferating Cells From Stem-Cell Derived Grafts

Stem-cell derived grafts hold great therapeutic promise but recent clinical cases have highlighted the potential dangers associated with the presence of proliferating cells in the graft. We have developed a method to specifically eliminate proliferating cells in stem cell-derived grafts of neurons and other cell-based therapies where the final target consists of post-mitotic cells.

Patent # JP7099967, AU2017290805, EP3478325

Application Number # PCT/US17/40303, CA3029582

Generation Of Dopaminergic Neurons

Methods and compositions for differentiating neuronal precursors into dopaminergic neurons are provided. Zoxazolamine is used in certain embodiments to promote or enhance dopaminergic differentiation. Also provided are neurotoxicity tests or screening methods using dopaminergic neurons generated via these methods.

Patent # US8815592

Application Number # PCT/US2011/033232

Methods And Probiotic Compositions For The Treatment Of Bone Disorders

Methods of treating osteoporosis and other bone density disorders with warm microbiome bacteria are provided. Related pharmaceutical and probiotic compositions are also provided.

Patent # US11541083, AU2019351019, EP3856147

Application Number # PCT/US19/53402, US18/060,134, CA3113448

METHODS AND PROBIOTIC COMPOSITIONS FOR THE TREATMENT OF METABOLIC DISEASES AND DISORDERS

Heat inactivated or dead Parabacteroides Goldsteinii may be used to increase insulin sensitivity, and treat diseases including obesity and diabetes. Methods of culturing bacteria in spermine and spermidine and using these compounds for the treatment of metabolic diseases are also provided. Additional microbiota and related compositions and methods for treating bone diseases and/or metabolic diseases are also provided.

Patent # US11883447, JP7761556, CN202080064409, AU2020348461

Application Number # PCT/US20/51581

Methods for Making and Using Differentiated Neural Cells

Methods for differentiating stem and progenitor cells into neural cells through an approach that excludes the use of SMAD or Noggin inhibition are provided. Methods for differentiating stem or progenitor cells into neural cells can include contacting cells with a compound selected from DMH1, DMH2, K02288, A8301, or combinations thereof.

Application Number # PCT/US2021/054462

NEURAL NETWORK SYSTEMS FOR smORF PEPTIDES

Shortstop methods and software are provided for identifying small open reading frame (smORF) peptides that may be excreted and/or have biological function.

Application Number # PCT/US24/59319, US18/975313

Stem Cell Clones With Defined Differentiation Capabilities

Methods for the selection of clones from a single stem cell line which exhibit improved differentiation properties is provided. In particular, the inventor has observed that specific subclones derived from a single embryonic stem cell line display a wide variety in their ability to differentiate into a specific cell lineage, such as dopaminergic neurons. This finding has allowed for the selection of specific subclones obtained via serial dilution which consistently exhibit improved differentiation properties.

Patent # US10947499

Application Number # US12/958,183

3D-Structure Of An Extracellcular Domain Of A B1 G-Protein

Method for identifying modulators of B1 G-protein coupled receptors. In particular, methods are provided for identifying an antagonist or selective agonist of the corticotropin-releasing factor receptor 2 (CRF-R2).

Patent # US7869958

A Conditional Gene Knock-Down System Using RNAi

Compositions and Systems for Regulation of Genes. Vectors and methods for controlled and/or inducible expression of small interfering RNA.

Patent # EP1563069, CA2506798

Application Number # US13/448580

APPARATUS AND METHODS FOR INTRA-VASCULAR LASER LITHOTRIPSY

Provided are apparatus and methods for the fracture of arterial calcifications. The apparatus can include (1) use of plastic catheters, which provide an advantage in that they are easier to process and to combine with optical elements, (2) a catheter design with a guide wire and an overlying balloon, (3) optical elements on plastic wires to focus the light into an absorbing fluid (e.g., ICG), and (4) approach that can allow multiple shock waves using a single fiber and laser system. Multiple shock-wave emitters can be included in a single fiber, and a laser system can be configured in real time to emit shock waves from any arbitrary combination of the emitters, allowing laser output to be controlled based on the size of a calcium deposit.

Application Number # PCT/US24/10920, US18/408284, EP24741904.7, AU2024207835, JP2025-540176, KR10-2025-7024693

Immunoreactive Polypeptides

Antigenic Ehrlichia proteins are provided. Ehrlichia proteins that exhibit antigenicity greater than TRP47 are provided and can be used for diagnosis of Ehrlichia and/or included in a vaccine composition.

Patent # US12461099, AU2019267569, MX430947

Application Number # PCT/US19/31137

Methods For Generating Engineered Enzymes

Methods for generating modified enzymes, such as proteases and kinases, that display altered or improved specificity and/or efficiency are provided. Yeast ER Sequestration Sequencing (YESS) and Next Generation Sequencing have been combined to produce high-throughput methods with very high specificity and accuracy. Since kinases represent important targets in oncology, these approaches may be used in diagnostic kits for personalized treatments for cancer by evaluating kinase activity from cell lysates to determine an appropriate treatment for the patient.

Patent # US10900059, EP3207150

Application Number # PCT/US15/55494

Methods for Making and Using Differentiated Neural Cells

Methods for differentiating stem and progenitor cells into neural cells through an approach that excludes the use of SMAD or Noggin inhibition are provided. Methods for differentiating stem or progenitor cells into neural cells can include contacting cells with a compound selected from DMH1, DMH2, K02288, A8301, or combinations thereof.

Application Number # PCT/US2021/054462

Methods For Predicting Kinase Inhibitor Resistance

YESS (yeast endoplasmic reticulum sequestration screening) methods are provided to predict if a particular kinase inhibitor (e.g., to treat a cancer) will be more or less susceptible to the emergence of resistance mutations during clinical use in vivo that may decrease the effectiveness of the kinase inhibitor. In some aspects, the YESS methodology is used to evolve kinases in the presence of kinase inhibitors. The mutations observed in the mutant kinases evolved in vitro have also been observed in cancers in vivo.

Patent # US16/178991

Application Number # PCT/US18/58834, US16/178991, AU2018358144, CA3079985, EP18874197.9

Methods Of Engineering Proteases And Other Enzymes Using Yeast

Provided are methods for generated proteases and kinases with altered or improved specificity or potency via the Yeast ER Sequestration (YESS) approach. TEV proteases with altered specificity or potency are also provided. The method generally involves expressing a library of proteases, having at least one randomized section, and a library of targets in yeast. Some embodiments may use a “library on library” approach. The yeast may then be sorted according to activity or specificity, e.g., using FACS.

Patent # US8945855, US9546359, EP2864480, CA2877346

Application Number # PCT2013047663

METHODS OF MICROBIOME CHARACTERIZATION AND MONITORING

Methods of microbiome characterization and monitoring using subspecies analysis by machine learning or artificial intelligence approaches are provided.

Application Number # PCT/US25/42133

Multi-Channel Orthogonal Confolutional Neural Networks

Provided are an apparatus and related methods to classify a plaque tissue present in the coronary artery using intravascular optical coherence tomography (IVOCT) images. The methods may use neural networks to analyze and classify elements from the imaging data provided.

Patent # US11779220

Application Number # PCT/US19/65850

NEURAL NETWORK SYSTEMS FOR smORF PEPTIDES

Shortstop methods and software are provided for identifying small open reading frame (smORF) peptides that may be excreted and/or have biological function.

Application Number # PCT/US24/59319, US18/975313

Stem Cell Clones With Defined Differentiation Capabilities

Methods for the selection of clones from a single stem cell line which exhibit improved differentiation properties is provided. In particular, the inventor has observed that specific subclones derived from a single embryonic stem cell line display a wide variety in their ability to differentiate into a specific cell lineage, such as dopaminergic neurons. This finding has allowed for the selection of specific subclones obtained via serial dilution which consistently exhibit improved differentiation properties.

Patent # US10947499

Application Number # US12/958,183

SYSTEMS AND METHODS FOR LASER-INDUCED CALCIUM FRACTURES

Methods and apparatuses related to fracture of arterial calcifications during coronary and peripheral intervention are provided. Studies are provided showing that light can be used to generate micro-cavitations and secondary calcium fracture in ex vivo human calcified coronary arteries.

Application Number # US17/548467, AU2021397309, CA3200965, EP21904479, JP2023-535463, CN-pending, KR10-2023-7021214

Systems and Methods for Ultrasound and Photoacoustic Guidance of Coronary Procedures

Apparatuses and methods for treatment of chronic total occlusion (CTO) of blood vessels (e.g., in the heart) based on and using an ICE-guided Cold Laser Wire (CLW) catheter are provided. The ICE-guided Cold Laser Wire (CLW) catheter can include: (a) a small, flexible and steerable catheter that can provide real-time ranging data, (b) laser cutting and cryogenic cooling that allows for crossing coronary CTOs more safely and without damage to the vessel wall, and (c) the calcium cutting laser allows true lumen crossing of CTOs with excessive calcification.

Application Number # PCT/US21/50147, US18/044408, AU2021340881, CA3192117, EP21867792, JP2023-516488

Transgenic Mice Deficient In Corticotropin-Releasing Factor Receptor 2 (CRFR 2)

Transgenic mice deficient in corticotropin-releasing factor receptor 2 (CRFR-2), a critical integrator of the hypothalamic-pituitary-adrenal (HPA) axis in response to stress. These mice are useful for the study of anxiety, depression, and the physiology of the HPA axis.

Patent # US7674463

Application Number # US09/714,692

Chimeric Immunogenic Polypeptides

Chimeric polypeptide constructs containing multiple Ehrlichia epitopes are provided. The chimeric molecules may be synthetic or recombinant polypeptides which may be used, e.g., for diagnostic or vaccination purposes.

Patent # US11780892, US11046734, US12552843

Application Number # PCT/US19/43840, AU2019311181, BR112021001420-9, CA3107319, EP19842185.1, CN201980059990.7, US19/532418

EHRLICHIA IMMUNODOMINANT PROTEINS

Antigenic proteins of Ehrlichia are identified, including newly identified immunodominant proteins. Such proteins can be used to diagnose ehrlichiosis or vaccinate against Ehrlichia. The identification of the immunodominant proteins was performed based on extensive analysis of proteins expressed by Ehrlichia.

Application Number # PCT/US24/60651

Ehrlichia Immunoreactive GP47 And GP36 Antigens For Diagnosis And Vaccination

Immunoreactive gp47 and gp36 proteins in Ehrlichia chaffeensis and E. canis are provided. These proteins may be used for diagnosis of Ehrlichiosis in humans and/or dogs. The proteins may also be included in vaccine compositions against Ehrlichia infection.

Patent # US9140702, US9645148, RE46254, MX296016, CA2612302, BR PI0611820-8

Application Number # US11/917390

IMMUNODOMINANT PEPTIDES

Synthetic immunoreactive peptides are provided and can be used to diagnose or vaccinate against Ehrlichia canis and/or Ehrlichia chaffeensis.

Patent # US 12,226,468

Application Number # PCT/US24/35561, US19/040,374

Immunoreactive Ehrlichia P120 / P140 Epitopes And Uses Thereof

Provided are peptides which can selectively bind Ehrlichia-specific anti-p 120 or anti-p 140 antibodies. Methods and kits utilizing the immunoreactive peptides are also provided. The immunoreactive peptides may be utilized, e.g., for determining whether or not a subject is infected with Ehrlichia chaffeensis or Ehrlichia canis. In certain embodiments, the immunoreactive peptides may be utilized in an ELISA or lateral flow assay

Patent # US8329189, CA2796563, EP2424880

Application Number # PCT/US2010/032744

Immunoreactive Ferric Binding Protein Of Ehrlichia

An immunoreactive ferric binding protein (Fbp) (38-kDa) protein of Ehrlichia canis. This protein may be used in vaccine compositions to immunize animals against E. canis.

Patent # US7722880, CA2555413

Application Number # 11/066648

Immunoreactive Polypeptides

Antigenic Ehrlichia proteins are provided. Ehrlichia proteins that exhibit antigenicity greater than TRP47 are provided and can be used for diagnosis of Ehrlichia and/or included in a vaccine composition.

Patent # US12461099, AU2019267569, MX430947

Application Number # PCT/US19/31137

PROTEINS FOR EHRLICHIA DIAGNOSIS AND VACCINATION

Antigenic Ehrlichia proteins are provided. The antigenicity of these proteins was compared with TRP47, and select exhibit antigenicity greater than TRP47. The proteins may be included in a diagnostic test for ehrlichiosis or in a vaccine composition.

Application Number # PCT/US21/31509

Vaccines For The Ehrlichioses Comprising GP19 Or VLPT Antigens

Vaccine compositions comprising gp19 of E. canis and TR6 containing ortholog (VLPT) in E. chaffeensis are provided. Synthetic and/or recombinant polypeptides corresponding to various regions of VLPT were used to localize major antibody epitopes to the TR-containing region. Major antibody epitopes were identified. The vaccine compositions may be used to protect against Ehrlichiosis.

Patent # US10131705, US9850295, US9605036, US9605035, EP2245049, KR1588736, MX314676, JP5677703, BR-PI0906429-0, CA2711499

Application Number # PCT/US09/030527