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US 2026/0274931 A1Published application
Methods of treating alzheimer's disease
AssigneeKlaritos, Inc.
InventorVijay RAMAKRISHNAN
Life of this patent
Estimating the term…
Abstract
Disclosed herein are methods of conducting clinical trials in Alzheimer's disease (AD). Methods of selecting a medicament and treating an AD subject are disclosed. Methods, systems, kits, and devices for selecting a subject in AD clinical trials and treatment protocols are disclosed herein.
Claims54
A method of conducting a clinical trial in Alzheimer's Disease (AD) subjects, comprising:
- a) stratifying AD subjects based on a combination of therapeutic mechanisms of action and disease subtypes to make enrollment decisions;
- b) administering to the stratified subsets or on a subject-by-subject basis, at least one of the following drug candidates:
- i) an anti-beta-amyloid (anti-Ab) antibody,
- ii) an anti-TNF biologic,
- iii) a B-cell depleting antibody,
- iv) a combination therapy consisting of an anti-Ab antibody and an anti-TNF biologic, or a combination therapy consisting of an anti-Ab antibody and a B-cell depleting antibody.
3 more elements
A clinical trial in AD subjects, the trial comprising:
- a) stratifying AD subjects based on a combination of therapeutic mechanisms of action and disease subtypes to make enrollment decisions;
- b) administering to the stratified subsets or on a subject-by-subject basis, at least one of the following drug candidates:
- i) an anti-Ab antibody,
- ii) an anti-TNF biologic,
- iii) a B-cell depleting antibody,
- iv) a combination therapy consisting of an anti-Ab antibody and an anti-TNF biologic, or a combination therapy consisting of an anti-Ab antibody and a B-cell depleting antibody.
3 more elements
A method of treating an AD patient using a precision medicine approach, comprising:
- a) stratifying AD subjects includes:
- i) determining a combination of therapeutic mechanisms of action, disease subtypes, ARIA/CAA immune mechanism, and FcGR functional polymorphisms, including FcGR-3A V/F158 and FcGR-2A H/R131 to make enrollment decisions;
- ii) measurement of biomarkers including Ab42/Ab40 ratio, phosphorylated-tau217 (P-tau217), and neurofilament light chain (NfL) in plasma or cerebrospinal fluid (CSF) to refine patient stratification and treatment selection;
- iii) measurement of immune cells including B-cell subsets and inflammatory macrophages, wherein the B-cell subsets include naïve, memory, and plasma B-cell subsets;
- iv) measurement of cytokines in peripheral blood, wherein the cytokines include TNF-a, IL-1, IL-6;
- b) administering at least one of the following treatments to the stratified subsets or on a patient-by-patient basis:
- i) an anti-Ab antibody therapy,
- ii) an anti-TNF therapy,
- iii) a B-cell depleting antibody therapy,
- iv) a combination therapy consisting of an anti-Ab antibody therapy and an anti-TNF therapy, or
- v) a combination therapy consisting of an anti-Ab antibody therapy and a B-cell depleting therapy;
- c) regularly monitoring the patient's cognitive and functional status using standardized outcome measures such as ADAS-Cog or CDR-SB scores to assess the effectiveness of the treatment and adjust the therapy as needed.
9 more elements
A method of administering a drug candidate in an AD subject enrolled in a clinical trial, wherein the trial protocol comprises:
- a) selecting the drug candidate based on stratification criteria that include functional polymorphisms, therapeutic mechanisms, ARIA/CAA incidence, disease subtypes, and biomarker profiles;
- b) the drug candidate being one or more of an anti-Ab antibody, an anti-TNF biologic, or a B-cell depleting antibody, administered either as a monotherapy or part of a combination therapy;
- c) evaluating treatment response by measuring changes in cognitive and functional status;
- and
- d) adjusting the drug candidate based on these evaluations.
2 more elements
A method of conducting a clinical trial in AD subjects with an underlying autoimmune disease or inflammatory disease, comprising:
- a) stratifying patients based on AD pathology, underlying autoimmune or inflammatory disease, and biomarkers indicative of disease subtypes;
- b) administering a drug candidate either as a monotherapy or part of a combination therapy, wherein the monotherapy or combination therapy comprises at least one of the following:
- i) an anti-Ab antibody, ii) an anti-TNF biologic, or iii) a B-cell depleting antibody;
- and
- c) assessing the dual effectiveness of the drug candidates on AD progression and the underlying condition through predefined clinical endpoints and biomarker changes.
2 more elements
A clinical trial in AD subjects with an underlying autoimmune disease or inflammatory disease, the trial comprising:
- a) stratifying patients based on AD pathology, underlying autoimmune or inflammatory disease, and biomarkers indicative of disease subtypes;
- b) administering a drug candidate either as a monotherapy or part of a combination therapy, wherein the monotherapy or combination therapy comprises at least one of the following:
- i) an anti-Ab antibody,
- ii) an anti-TNF biologic, or
- iii) a B-cell depleting antibody;
- and
- c) assessing the dual effectiveness of the drug candidates on AD progression and the underlying condition through predefined clinical endpoints and biomarker changes.
4 more elements
A method of stratifying AD patients for targeted treatment, comprising:
- determining a combination of therapeutic mechanisms of action and FcGR functional polymorphisms, wherein the polymorphisms include FcGR-3A V/F158 and FcGR-2A H/R131, wherein the therapeutic mechanisms include antibody dependent cellular cytotoxicity (ADCC) or antibody dependent cellular cytotoxicity (ADCP);
- b) correlating the incidence of amyloid-related imaging abnormalities (ARIA) or cerebral amyloid angiopathy (CAA) immune mechanism is correlated to the FcGR functional polymorphisms, wherein the polymorphisms include FcGR-3A V/F158 and FcGR-2A H/R131;
- c) measurement of biomarkers including Ab42/Ab40 ratio, phosphorylated-tau217 (P-tau217), and neurofilament light chain (NfL) in plasma or cerebrospinal fluid (CSF) to refine patient stratification and treatment selection;
- d) measurement of immune cells including B-cell subsets and inflammatory macrophages, wherein the B-cell subsets include naïve, memory, and plasma B-cell subsets;
- wherein the measurement includes depletion or repopulation of the immune cells in peripheral blood;
- e) measurement of cytokines in peripheral blood, wherein the cytokines include TNF-a, IL-1, IL-6;
- f) measurement of disease subtypes including from the group consisting of cognitively unimpaired (CU), subjective cognitive decline (SCD), mild cognitive impairment (MCI), or AD dementia state;
- and
- g) selecting an appropriate therapy for each patient based on a combination of genetic and immune biomarkers, and clinical data, aiming to slow the progression of AD or improve cognitive and functional outcomes.
6 more elements
A method of treating an AD patient, the method comprising:
- a) administering an anti-Ab antibody as a first therapy to the subject;
- b) subsequent to or concurrent with step (a), administering a second therapy selected from the group consisting of an anti-TNF biologic and a B-cell depleting antibody;
- c) determining the patient's responsiveness to the first and second therapy based on changes in at least one of cognitive function and functional status;
- and
- d) adjusting the treatment regimen based on the determined responsiveness, wherein the adjustment comprises modifying the dose, frequency, or combination of the first therapy and second therapy to optimize therapeutic outcomes for the patient.
2 more elements
A method of conducting a classical clinical trial in an unstratified population of AD subjects, comprising:
- a) enrolling subjects diagnosed with AD without prior stratification based on mechanism of action of therapies, mechanism of ARIA or CAA incidence;
- b) randomly assigning the enrolled subjects to receive at least one therapy selected from the group consisting of:
- i) an anti-Ab antibody as a monotherapy,
- ii) an anti-TNF biologic as a monotherapy,
- iii) a B-cell depleting antibody as a monotherapy,
- iv) a combination therapy of an anti-Ab antibody and an anti-TNF biologic,
- v) a combination therapy of an anti-Ab antibody and a B-cell depleting antibody, or
- vi) a combination therapy of an anti-TNF biologic and a B-cell depleting antibody;
- c) monitoring the subjects for changes in cognitive and functional outcomes over a predetermined trial period;
- and
- d) comparing the efficacy and safety of the administered therapies across the unstratified AD population to identify effective treatment(s) for AD.
8 more elements
A classical clinical trial in an unstratified population of AD subjects, the trial comprising:
- a) enrolling subjects diagnosed with AD without prior stratification based on mechanism of action of therapies, mechanism of ARIA or CAA incidence;
- b) randomly assigning the enrolled subjects to receive at least one therapy selected from the group consisting of:
- i) an anti-Ab antibody as a monotherapy,
- ii) an anti-TNF biologic as a monotherapy,
- iii) a B-cell depleting antibody as a monotherapy,
- iv) a combination therapy of an anti-Ab antibody and an anti-TNF biologic,
- v) a combination therapy of an anti-Ab antibody and a B-cell depleting antibody, or
- vi) a combination therapy of an anti-TNF biologic and a B-cell depleting antibody;
- c) monitoring the subjects for changes in cognitive and functional outcomes over a predetermined trial period;
- and
- d) comparing the efficacy and safety of the administered therapies across the unstratified AD population to identify effective treatment(s) for AD.
8 more elements
A method of administering a classical treatment protocol in an unstratified population of AD patients, comprising:
- a identifying patients diagnosed with AD without prior stratification, wherein the stratification includes the mechanisms of action of therapies, the mechanism of ARIA or CAA incidence;
- b) administering to the patients a therapy selected from the group consisting of:
- i) an anti-Ab antibody as a monotherapy,
- ii) an anti-TNF biologic as a monotherapy,
- iii) a B-cell depleting antibody as a monotherapy,
- iv) a combination therapy of an anti-Ab antibody and an anti-TNF biologic,
- v) a combination therapy of an anti-Ab antibody and a B-cell depleting antibody, or
- vi) a combination therapy of an anti-TNF biologic and a B-cell depleting antibody;
- c) monitoring therapeutic outcomes and side effects in the treated patients over a predetermined treatment period;
- and
- d) adjusting the therapy based on the observed efficacy and side effects in the patients, aiming to optimize therapeutic outcomes in the unstratified AD population.
8 more elements
A pharmaceutical product label for treating AD in a patient, comprising:
- a) instructions for administering a monotherapy or combination therapy comprising an anti-Ab antibody and at least one of an anti-TNF biologic or a B-cell depleting antibody;
- b) indications for use based on therapeutic mechanisms, ARIA/CAA incidence mechanism, disease subtypes, the FcGR functional polymorphisms, and biomarker profiles to make treatment decisions;
- c) guidelines for dose adjustments and administration frequency based on patient responsiveness and disease progression;
- d) a warning section detailing potential side effects and contraindications specific to the therapies;
- and
- e) a section on monitoring requirements for cognitive and functional status to assess therapy effectiveness.
3 more elements
A kit for stratifying AD patients for targeted therapy selection, comprising:
- a) reagents for detecting ATN levels in a biological sample;
- b) reagents for genotyping the FcGR functional polymorphisms in the patient;
- c) reagents for measuring immune cells in peripheral blood;
- d) reagents for measuring cytokines in peripheral blood;
- e) instructions for interpreting the presence of ATN levels and FcGR functional polymorphisms to stratify patients into treatment groups;
- f) guidelines for selecting appropriate AD therapies based on stratification;
- and
- g) packaging material indicating the intended use of the kit for AD patient stratification and therapy selection.
5 more elements
A method of providing prior authorization for AD therapies, comprising:
- a) receiving patient data, including the FcGR functional polymorphisms and ATN levels in a biological sample;
- b) stratifying the patient into specific treatment groups based on the received patient data;
- c) selecting an appropriate AD therapy for the patient from the group consisting of an anti-Ab antibody, an anti-TNF biologic, a B-cell depleting antibody, or a combination thereof, based on the stratification;
- d) generating a prior authorization request that includes the selected therapy and justification based on the patient's stratification;
- and
- e) transmitting the prior authorization request to a payer for approval, wherein the approval is based on the alignment of the selected therapy with the patient's stratification.
3 more elements
Dependencies are inferred from the claim text.