Healthcare & Life Sciences

INMODE Nasal Septum Treatment Device, 20 Claims, Granted Apr 28

USPTO granted patent US12611244B1 to INMODE LTD. on April 28, 2026, covering a device and method for nasal septum treatment using radiofrequency energy. The patent, invented by Michael Kreindel, includes 20 claims and describes reshaping the nasal septum by creating multiple holes in cartilage and applying RF energy to ablate tissue while minimizing damage to surrounding epithelial and mucosal tissues. The application was filed November 3, 2021, under application number 17517790.

Power monitoring circuitry and method for reducing leakage current in RF generators

The USPTO granted Patent US12611243B2 to Medtronic Advanced Energy LLC on April 28, 2026, covering an electrosurgical unit with power monitoring circuitry designed to reduce RF generator leakage current. The invention uses a transformer to transform leakage current to a feedback current in a reverse direction across an isolation barrier, with a control circuit that modulates pulse width to regulate the RF input signal. The patent contains 16 claims and was filed on July 7, 2022.

CurvaFix Intramedullary Fixation Patent, 3 N·m Torque

CurvaFix Intramedullary Fixation Patent, 3 N·m Torque

Catheter System for Stenosis Treatment, Back Leg Pain

Catheter System for Stenosis Treatment, Back Leg Pain

Screw Extraction Shaft, DEPUY SYNTHES, 28th Apr

USPTO granted patent US12611242B2 to DEPUY SYNTHES PRODUCTS, INC. on April 28, 2026 for a bone screw extraction device featuring a shaft with a distal tip having fingers configured to be received within a driving recess of a bone screw and channels extending along an exterior surface. The patent, filed on April 25, 2022 under application number 17660527, contains 9 claims. Inventors include Simon Scherrer, Mario Wyss, and Gregor Spreiter.

Wedge osteotomy devices, mid-foot disorder treatment, B2 grant, 28th Apr

Wedge osteotomy devices, mid-foot disorder treatment, B2 grant, 28th Apr

Implant with Intramedullary and Offset Extramedullary Portions, Wright Medical

Implant with Intramedullary and Offset Extramedullary Portions, Wright Medical

Load Sharing Bone Plate, Avanti Orthopaedics

Load Sharing Bone Plate, Avanti Orthopaedics

Orthopedic Bone Screw Patent US12611239B2 by Voom Medical

The USPTO granted Patent US12611239B2 to Voom Medical Devices, Inc. on April 28, 2026, covering an orthopedic bone screw with dual-thread configuration for use in surgical procedures. The invention features a shank with helical threading, including a first purchase zone with thread pitch configured for cancellous bone and a second purchase zone for cortical bone, both compression-neutral. The patent application 18518376 was filed November 22, 2023, and includes 17 claims.

GLW Inc Intramedullary Nail Patent, 28th Apr

GLW Inc Intramedullary Nail Patent, 28th Apr

US12612427B2 - SGLT1 Inhibitor Patent to Shanghai Zheye Biotechnology

USPTO granted Patent US12612427B2 to Shanghai Zheye Biotechnology Co. Ltd. on April 28, 2026, covering an aryl glucoside derivative that inhibits sodium-glucose co-transporter 1 (SGLT1). The patented compound and pharmaceutical compositions may be used for treating diabetes, cardiovascular and cerebrovascular diseases, weight loss, fatty liver disease, constipation, metabolism-related diseases, and tumor treatment. The patent application was filed November 24, 2020 (Application No. 18023883) and contains 14 claims.

US12612426B2 - Aryl Glucoside SGLT1 Inhibitor, Shanghai Zheye Biotechnology

USPTO granted Patent US12612426B2 to Shanghai Zheye Biotechnology Co. Ltd. on April 28, 2026, covering an aryl glucoside derivative that inhibits sodium glucose cotransporter 1 (SGLT1). The patent lists four inventors: Haibo Wang, Fengtian Du, Qiang Zhang, and Na Guo. The patented compound and its pharmaceutical compositions are intended for treating diabetes, cardiovascular and cerebrovascular diseases, weight loss, fatty liver, constipation, metabolism-related diseases, and tumors. The application was filed on November 24, 2020, under application number 18023878, with 14 claims allowed.

Crystalline Heterocyclic Compound Patent Granted to JW Pharmaceutical

The USPTO granted Patent US12612405B2 to JW Pharmaceutical Corporation on April 28, 2026, covering a novel polymorph of the heterocyclic compound 1-(8-bromopyrido[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-4-yl)-N-methylazetidin-3-amine hydrogen sulfate monohydrate. The patent application was filed March 29, 2022 under application number 18283916, with Suha Park and Seiho Chin listed as inventors. The granted patent contains 12 claims and covers pharmaceutical compositions using this crystalline form along with methods of treating atopic dermatitis, itch, pruritus, and chronic idiopathic urticaria subtypes.

Deuterated Selenophenochromenes for Cancer Treatment

USPTO granted Patent US12612417B2 to Latvian Institute of Organic Synthesis on April 28, 2026, covering deuterated selenophenochromene derivatives designed for cancer treatment. The patent, with 10 claims classified under A61P 35/00 (antineoplastic activity), names Pavels Arsenjans as inventor and was filed on July 21, 2020 under application number 17785205. This grant confers exclusive intellectual property rights to the assignee but does not impose regulatory compliance obligations on third parties.

2028 Medicaid HCBS Quality Measure Set, Comment Deadline May 28

CMS is seeking public comment on the 2028 HCBS Quality Measure Set, which establishes nationally standardized quality measures for Medicaid-funded home and community-based services. The notice proposes 23 mandatory measures including experience of care surveys, assessment measures, and administrative data measures, plus voluntary measures (LTSS-4 and MLTSS-5). States would be required to report 9-19 mandatory measures depending on populations served and surveys selected. Stratified data reporting by geography would be phased in at 25% by July 9, 2028, 50% by July 9, 2030, and 100% by July 9, 2032. Comments are due May 28, 2026.

BioNTech SE Individualized Cancer Vaccine Patent Granted US12611449B2

BioNTech SE has been granted US Patent 12611449B2 (Kind B2) for individualized cancer vaccines specific to a patient's tumor, based on transcriptome analysis of tumor specimens to identify RNA transcripts excessively upregulated in the patient's cancer cells. The inventors are Ugur Sahin, Mathias Vormehr, and Thomas Bukur. The patent, filed July 23, 2019, contains 8 claims and covers vaccines that induce immune responses against tumor-associated antigens by breaking self-tolerance.

Centessa A1AT Deficiency Treatment Patent US12611402B2

Centessa Pharmaceuticals (UK) Limited has been granted US Patent 12611402B2 for carboxylic acid compounds and pharmaceutical compositions for treating alpha-1 antitrypsin deficiency (A1AT/AATD). The patent, which names Nigel Ramsden, David John Fox, James Andrew Huntington, and James Michael Tomlinson as inventors, was filed on June 13, 2022 and issued April 28, 2026. The patent contains 17 claims covering compounds classified under CPC categories A61K 31/451, A61K 31/4015, and A61K 31/4708.

Tiratricol Drug Compositions for MCT8 Deficiency - US12611383B1

The USPTO granted US Patent 12611383B1 to Rare Thyroid Therapeutics International AB covering pharmaceutical compositions of tiratricol and/or salts thereof for treating MCT8 deficiency. The patent, with 19 claims, names Katayoun Welin-Berger as inventor and was filed on July 7, 2025. Patent grants confer exclusive market rights to the assignee for the claimed compositions and methods of use.

Inhalable Rapamycin PAH Treatment, OrphAI Therapeutics

The USPTO granted Patent US12611398B2 to OrphAI Therapeutics Inc. on April 28, 2026, covering methods and compositions for treating pulmonary arterial hypertension using inhalable rapamycin formulations. The patent application, filed on October 14, 2022 under application number 17965859, contains 36 claims and is classified under CPC codes A61K 31/436, A61K 9/0075, and A61K 9/12. Inventors include Thomas Armer, Lawrence S. Melvin Jr., Jonathan M. Rothberg, and Henri Lichenstein.

Douglas Pharmaceuticals Extended Release Formulation for Treatment-Resistant Depression and Anxiety

The USPTO granted patent US12611386B2 to Douglas Pharmaceuticals Ltd. on April 28, 2026, covering an oral extended release pharmaceutical formulation for treating treatment-resistant depression and treatment-resistant anxiety. The patent (23 claims, CPC classification A61K 31/2031) names Paul William Glue, Natalie June Medlicott, Peter William Surman, and Yuefeng Long as inventors, with a filing date of September 22, 2021 and application number 18028202. Patent grants are final, binding intellectual property rights that give the assignee exclusive rights to the claimed invention.

Recombinant adeno-associated virus vectors to target medullary thyroid carcinoma

The USPTO granted Patent US12611468B2 to the University of Florida Research Foundation, Incorporated on April 28, 2026, covering recombinant adeno-associated virus (rAAV) vectors engineered to target medullary thyroid carcinoma cells. The patent (10 claims) includes mutations in surface-exposed amino acids of the rAAV particle and a truncated calcitonin promoter to enhance transduction of carcinoma cells. The filing date was February 1, 2022, under application number 17590557.

Gilead Sciences HIV-1 Immune Response Patent, Adenovirus Vector and TLR7 Agonist

The USPTO has granted US Patent 12,614,453 B2 to Gilead Sciences, Inc. covering methods of inducing an HIV-1-specific immune response using a chimpanzee adenovirus vector encoding an HIVACAT T-cell immunogen in combination with a TLR7 agonist. The patent also protects compositions and kits for this combination and their use in treating or preventing HIV infection in humans. The patent contains 25 claims and names five inventors: Romas Geleziunas, Devi Sengupta, Christian Brander, Beatriz Mothe Pujadas, and Ian McGowan.

REGENXBIO Granted US12612644B2 for Scalable Recombinant AAV Production Using HDAC Inhibitor

USPTO granted Patent US12612644B2 to REGENXBIO INC. on April 28, 2026, covering methods for producing recombinant Adeno-Associated Virus (rAAV) particles using histone deacetylase (HDAC) inhibitors. The patent names Michael Gillmeister, Miguel Valle, Robert Stadelman, Franz Gerner, Matthieu Guibert, and Bhargavi Kondragunta as inventors. The application (No. 17267247) was filed August 9, 2019, and the granted patent contains 14 claims.

Harvard AAV Gene Therapy Patent for Hearing Loss, Blindness

The USPTO granted Patent US12612645B2 to President and Fellows of Harvard College on April 28, 2026. The patent covers isolated nucleic acids, vectors, and rAAV.9.PHP.B compositions encoding mini-PCDH15, along with methods for treating hearing loss and/or blindness, particularly Usher Syndrome type IF. The patent also covers gRNA associated with base editors to correct PCDH15 mutations. Biotechnology firms and researchers developing gene therapies for inherited hearing and vision disorders should review this patent landscape. The 15 granted claims provide Harvard with broad protection over AAV-mediated mini-PCDH15 expression for therapeutic applications.

Live Imaging System to Visualize Retro-Transcribed Viral DNA Genome, Institut Pasteur, US Patent Grant US12613239B2

The USPTO granted US Patent 12,613,239 B2 to Institut Pasteur on April 28, 2026, covering a live imaging system for visualizing retro-transcribed viral DNA using the HIV-1 ANCHOR system. The patent claims a recombinant lentiviral vector with an ANCH sequence, a eukaryotic cell containing the integrated vector, and a method of observing lentiviral DNA through fluorescent protein detection. The invention was filed on April 11, 2020, under application number 17607118, with 18 claims. Applications include antiretroviral drug screening and potential extension to SARS-CoV-2 antiviral research.

Aβ34 Antibody Diagnoses Alzheimer's, McGill Patent

USPTO granted patent US12613249B2 to The Royal Institution for the Advancement of Learning/McGill University covering an anti-Aβ34 antibody and its use for diagnosing Alzheimer's disease. The diagnostic method comprises obtaining a patient sample, detecting Aβ34 levels by contacting the sample with the anti-Aβ34 antibody, and diagnosing Alzheimer's when Aβ34 is detected alone or in combination with Aβ42 ratio analysis. The patent names inventors Gerhard Multhaup and Adeola Shobo and was granted on April 28, 2026.

US12612638B2 - Fusion Constructs for Biopharmaceutical Polypeptide Expression in Cyanobacteria

The USPTO granted Patent US12612638B2 to The Regents of the University of California on April 28, 2026, covering fusion constructs designed to express biopharmaceutical polypeptides in cyanobacteria and microalgae. The patent names Anastasios Melis, Nico Betterle, Diego Hidalgo Martinez, and Andrew C. Saphire as inventors and includes 14 claims. The filing was received September 11, 2020, under application number 17642330. Patent holders and biotechnology firms developing cyanobacteria-based expression systems should review this grant for potential freedom-to-operate implications.

US12613237B2 - Montana Molecular Biosensors for Detecting Arrestin Signaling

USPTO granted patent US12613237B2 to Montana Molecular, LLC on April 28, 2026, covering fluorescent reporter constructs and methods for detecting arrestin cellular signaling changes in cells. The patent, filed on July 30, 2019, includes 10 claims and CPC classifications in C07K, G01N domains. Inventors Thomas Hughes and Paul Tewson developed nucleic acid-based biosensors that can be packaged into vectors and cells for research and diagnostic applications targeting G-protein-coupled receptor signaling pathways.

Phase 1b Study of TRICK-NK With T-Dxd in Treatment-Refractory Breast Cancers

A Phase 1b clinical trial (NCT07553390) evaluating TRICK-NK (TGFBR-2 KO CD70 CAR NK cells) in combination with trastuzumab deruxtecan (T-Dxd) in participants with treatment-refractory breast cancers has been registered. The study comprises dose escalation (Part 1), dose expansion (Part 2), and an optional schedule optimization phase testing shorter intervals between NK cell infusion and T-Dxd dosing. The trial will assess maximum tolerable dose and safety of the combination regimen.

CMD Diet Pilot Trial for Recurrent Glioma Patients

This registry entry documents a new randomized, blinded interventional pilot study (NCT07553520) testing a cysteine/methionine deprivation (CMD) diet in up to 30 patients with recurrent glioma. Participants will be assigned to either a control diet or CMD diet for 2, 4, or 7 days before standard treatment, with researchers measuring glutathione metabolite levels, tumor cell behavior, and gut bacteria. Patients will be followed for progression-free survival and overall survival for up to 1 year.

Phase 3 Trial Comparing Perioperative, Adjuvant, Neoadjuvant Toripalimab for Resectable Stage II-IIIA NSCLC

A randomized, open-label, multi-center Phase III clinical trial (NCT07554846) comparing three immunotherapy strategies—perioperative, neoadjuvant, and adjuvant—using Toripalimab in patients with resectable stage II-IIIA non-small cell lung cancer (NSCLC) without EGFR/ALK mutations. The trial, conducted by the Eastern Cooperative Thoracic Oncology Project (ECTOP) as protocol ECTOP-1030, is registered on ClinicalTrials.gov with an estimated start date.

Hybrid Body Awareness Intervention for Menstrual Outcomes in Adolescent Girls

A new randomized controlled clinical trial registered as NCT07554053 will evaluate the effect of a hybrid body awareness-based intervention on menstrual symptoms, menstrual attitudes, and self-regulation levels in post-menarche adolescent girls. The study, registered April 28, 2026, lists 'Menstruation' and 'Adolescent Health' as conditions. Healthcare providers and clinical investigators researching adolescent menstrual health may need to be aware of this ongoing trial when considering similar interventions or study participation for their patients.

Color Doppler Twinkling Artifact Imaging for Breast Clip Visibility in 86 Patients

A new single-center retrospective observational study (NCT07554781) was registered on ClinicalTrials.gov evaluating the color Doppler twinkling artifact feature to improve visibility of breast tissue marker clips within breast tissue and axillary lymph nodes. The study will enroll approximately 86 female patients with 110 clips who underwent breast tissue marker clip placement with corresponding preoperative imaging data from GE-10 or Siemens ultrasound systems between October 2024 and October 2025. The primary endpoint is the proportion of subjects whose implanted clips exhibit the characteristic twinkling artifact on color Doppler ultrasound imaging, reported with a 95% confidence interval.

Photobiomodulation Laser for Reticular Pseudodrusen in AMD, 12-Month Trial

A randomized, sham-controlled Phase II clinical trial (NCT07554690) will evaluate whether photobiomodulation—a non-invasive low-energy laser therapy using specific wavelengths of light—can improve visual function and retinal structure in patients with early age-related macular degeneration who have reticular pseudodrusen. Participants (n=24) will be randomized to active photobiomodulation or sham treatment, with assessments over 12 months. The primary goal is to determine whether photobiomodulation can slow disease progression and improve low-light visual performance.

A Multilevel Intervention to Prevent Noise Exposure in Farmworkers

This ClinicalTrials.gov registry entry describes a randomized controlled trial testing a multilevel hearing protection program for farmworkers exposed to occupational noise from machinery. Farms will be randomly assigned to receive the intervention (educational video, group discussion, and hands-on hearing protection training for workers; supervisor training) or to a comparison group. Participants will wear dosimeters during work shifts before the program and approximately one month later to measure noise exposure, and will complete surveys on knowledge, attitudes, and behaviors related to hearing protection. A subset of participants will be interviewed to assess barriers and facilitators to program implementation. Results are intended to inform future hearing health improvement efforts in agricultural settings.

Plasma Therapy for Diverse Wounds - 500-Patient Observational Study

A prospective, multicenter, real-world observational study (NCT07553689) evaluating plasma device therapy added to standard wound care has been registered with ClinicalTrials.gov. The study will enroll 500 patients receiving plasma therapy plus standard wound care and 500 matched controls receiving standard wound care alone across multiple hospitals in China. The primary outcomes include wound healing rate at 4 weeks, time to complete wound closure, pain relief, scar formation, and side effects, with follow-up extending up to 6 months. The study covers acute wounds (burns, surgical incisions), chronic wounds (diabetic foot ulcers, pressure injuries), post-grafting wounds, and sutured wounds.

Feasibility Study of Co-designed Pre-radiotherapy Exercise Programme for Lung Cancer

A single-arm feasibility study will evaluate a co-designed, pre-radiotherapy exercise programme for patients with stage I-III non-small cell lung cancer. Participants will complete twenty, 20-minute supervised exercise sessions on a stationary exercise bike, performed immediately before each radiotherapy treatment at one of four personalised intensity levels. The study will monitor recruitment rates, session attendance, adherence to prescribed intensities, and adverse events to assess programme acceptability and safety, supplemented by qualitative interviews with participants, family members, and healthcare professionals.

Bio-flexible Spinal Fixation Apparatus for Preventing Fatigue Fracture

USPTO granted Patent US12611232B2 to inventor Kyung-Woo Park on April 28, 2026, for a bio-flexible spinal fixation apparatus designed to prevent fatigue fracture after spinal fixation surgery. The device features an eccentric coil rod design allowing natural flexion and extension motion post-surgery, with the rod including a straight part and a coil part wound at a predetermined angle. The patent application (18329250) was filed June 5, 2023, and the patent contains 11 claims under CPC classifications A61B 17/7028 and A61B 17/7005.

US12611233B2 Bone anchor housing limiter

The USPTO granted Patent No. US12611233B2 to Highridge Medical, LLC on April 28, 2026. The patent covers a bone anchor system comprising a fastener with a shaft, anchoring projection, and head; a rod housing connected to the fastener head; and a directional component with an outer diameter larger than the shaft diameter. The directional component includes a locking mechanism configured to engage the rod housing to limit housing movement during surgical fixation procedures. The patent contains 22 claims and was filed on January 23, 2024. Medical device manufacturers developing orthopedic surgical fixation products should evaluate this intellectual property for licensing or design-around considerations.

Spinal Rod Patent US12611231B2, Spinal Resources, 28th Apr

USPTO granted patent US12611231B2 to Spinal Resources, Inc. on April 28, 2026. The patent covers spinal rods comprising at least two segments with different constant diameters connected by a tapered transition region, plus at least one curve extending along the segments. The filing date was December 7, 2023, with application number 18532262.

Universal Fixator Clamp, Orthopedic Designs, Apr 28

USPTO granted patent US12611229B2 to Orthopedic Designs North America, Inc. on April 28, 2026, for a universal fixator clamp used in external fixation systems. The invention includes a torquing apparatus with multiple arms that engage complementary recesses in a proximal head to prevent patients from disengaging the clamp once tightened. The patent application (18612547) was filed on March 21, 2024, and the granted patent contains 6 claims.

Spinal Fixation Polyaxial Pedicle Screw Assigned to VB Spine US Opco LLC

The USPTO granted US Patent 12611234B2 on April 28, 2026, to assignee VB Spine US Opco LLC for a polyaxial pedicle screw system used in spinal fixation surgeries. The patent, invented by Larry E. McClintock, contains 15 claims covering the screw's housing, bone screw member, friction plug, anvil, and compression ring or cap configuration. This grant establishes exclusive IP rights for the disclosed spinal fixation device architecture.

Smith & Nephew Patent, Detachable Geared-Motor Strut Assembly for Spatial Frames

The USPTO granted Patent US12611228B2 to Smith & Nephew, Inc. on April 28, 2026, covering a detachable geared-motor assembly for motorizing a strut in a spatial frame. The patent claims priority to Application No. 18839091, filed February 14, 2023, and contains 23 claims under CPC classifications A61B 17/645, A61B 17/66, A61B 2017/00221, and A61B 2017/00398. Inventors include Paul Bell, Sied Janna, Darren J. Wilson, Andrew P. Noblett, Brian Roberts, Johnny R. Mason, and Scott Smyth. The geared-motor assembly is described as a standalone device including a microprocessor, printed-circuit board, and power supply for controlling the strut without external wires or a centralized controller. Competitors developing motorized spatial frame systems should review this patent for potential infringement exposure.

Vanderbilt University Patent, Medical Device Delivery System

Vanderbilt University has received US Patent 12611227B2 titled 'Medical device delivery apparatus and method.' The patent covers a delivery device configured to deliver a medical device into a patient, including a distal ring, transition tunnel, and proximal chute. The patent was granted on April 28, 2026 with 18 claims and a filing date of May 28, 2021. This patent represents intellectual property protection for medical device delivery technology developed by Kent K. Higdon.

Newmanbrain Brainwave Reading Apparatus Design USD1124354S1

The USPTO granted design patent USD1124354S1 to Newmanbrain, S.L. for a brainwave reading apparatus on April 28, 2026. The patent application was filed on October 22, 2024 under application number 29969433, with one claim covering the ornamental design of the device. The patent covers CPC classifications spanning brainwave monitoring, neurostimulation, and optical display components.

Electrode Patch, USD1124357S1, Y-BRAIN INC

Design patent USD1124357S1 for an electrode patch for biological signal measurement was granted to Y-BRAIN INC. by the USPTO. The patent application was filed on April 30, 2025, assigned application number 30001972, with one design patent claim. The CPC classifications span multiple medical device categories including A61B 5/0404, A61B 5/0416, A61B 5/0422, A61B 5/0424, A61B 5/04012, A61B 5/04082, A61B 5/04085, A61B 5/04087, A61B 5/6841, A61N 1/046, A61N 1/0472, and A61N 1/0476.

Medtronic Implantable Cardiac Monitor Design Patent USD1124345S1

The USPTO granted Medtronic, Inc. Design Patent USD1124345S1 for an implantable cardiac monitor on April 28, 2026. The patent application was filed on April 30, 2024 under Application No. 29940020, with three inventors: Matthew T. Vanderpool, Michael R. Klardie, and Kris A. Peterson. The patent contains one design claim covering the ornamental appearance of the medical device.

Electrode Patch Design Patent USD1124356S1 by Y-BRAIN INC

The USPTO granted Design Patent USD1124356S1 to Y-BRAIN INC on April 28, 2026, for an electrode patch for biological signal measurement. The patent was filed on April 30, 2025, under application number 30001969, with inventors Yoon Kyoung Hong, Tae Nam Kim, and Ki Won Lee. CPC classifications span A61B diagnostic/surgical categories and A61N electrotherapy categories.

Nitrile SUMO Inhibitors for Cancer Treatment

The USPTO granted Patent US12612414B2 to CIT Therapeutics, Inc. on April 28, 2026, covering nitrile-containing compounds that inhibit Small Ubiquitin-like Modifier (SUMO) proteins. The patent includes 18 claims and names six inventors: Miles Douglas Kubota, Andrew S. Tasker, Fang-Tsao Hong, Mary Walton, Victor J. Cee, and Peter Buchowiecki. The compounds are directed toward use in cancer treatment, with CPC classification C07D 495/04 in organic chemistry.

Vertex CFTR Modulator Patent Cystic Fibrosis Apr 28 2026

The USPTO granted Patent US12612416B2 to Vertex Pharmaceuticals Incorporated on April 28, 2026, covering modulators of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) with the core structure. The patent includes 23 claims and covers pharmaceutical compositions containing at least one such modulator, methods of treating cystic fibrosis, combination therapies, and processes and intermediates for making the modulators. The application was filed on October 6, 2021, under Application No. 18248065.