Diagnostic methods and apparatus

• US 10,398,592 B2
• Filed: 06/28/2012
• Issued: 09/03/2019
• Est. Priority Date: 06/28/2011
• Status: Active Grant

• Current Assignee: Forsight Vision4, Inc. (Roche Holding AG)
• Original Assignee: Forsight Vision4, Inc. (Roche Holding AG)
• Inventors: Erickson, Signe, Doud, Darren, de Juan, Jr., Eugene, Alster, Yair, Reich, Cary J., Farinas, Kathleen Cogan
• Primary Examiner(s): Mensh, Andrew J
• Application Number:
  US14/129,200
• Publication Number:
  US 20140221941A1
• Time in Patent Office: 2,623 Days
• Field of Search: 604294
• CPC Class Codes: A61B 10/0045 Devices for taking samples of body liquids devices for taking blood samples A61B5/15
• CPC Class Codes: A61F 2250/0067 Means for introducing or releasing pharmaceutical products into the body
• CPC Class Codes: A61F 9/0017 implantable in, or in contact with, the eye, e.g. ocular inserts
• CPC Class Codes: A61P 27/02 Ophthalmic agents

Abstract

An apparatus to treat a patient comprises a container to receive fluid of a device implanted in the eye. The fluid of the device can be analyzed to determine a component of the vitreous humor of the eye.

Claims

1. A method of collecting a sample of fluid from a reservoir chamber of a therapeutic device having a porous structure and implanted in an eye, the method comprising:

providing a cartridge configured to couple the implanted therapeutic device to a syringe containing a therapeutic fill volume, the cartridge comprising;

a connector configured to couple the cartridge to the syringe;

at least one needle having a first lumen configured to penetrate the implanted therapeutic device;

a container coupled to the cartridge and in fluid communication with a second lumen extending through the at least one needle; and

a porous vent structure coupled to a proximal, downstream end of the container, the porous vent structure configured to allow air to pass through the porous vent structure while preventing liquid from passing through the porous vent structure upon being wetted by a sample of displaced liquid from the reservoir chamber,

wherein the cartridge is adapted to simultaneously displace liquid from the reservoir chamber through the second lumen into the container while injecting the therapeutic fill volume from the syringe through the first lumen into the reservoir chamber of the implanted therapeutic device such that the cartridge collects the sample of displaced liquid from the reservoir chamber in the container for use in one or more analyses,

wherein the sample of displaced liquid comprises;

liquid of the eye comprising one or more markers of the eye accumulated in the reservoir chamber through the porous structure over a period of time; and

a therapeutic agent formulation remaining in the reservoir chamber after the period of time and prior to injecting the therapeutic fill volume from the syringe, the therapeutic agent formulation comprising one or more non-pharmacologic components and an amount of a therapeutic agent.

2. The method of claim 1, wherein the liquid of the eye comprises an aqueous humor or a vitreous humor fluid of the eye.

3. The method of claim 1, wherein the one or more markers of the eye is selected from the group consisting of one or more of a genetic marker, genomic expression of a marker, a protein marker, a protein biomarker of ocular disease, a biomarker having a linkage to an ocular disease, a biomarker having a linkage to AMD, a biomarker associated with AMD, a biomarker corresponding to a conversion from dry AMD to wet AMD, a biomarker comprising an early predictor of conversion of wet AMD to dry AMD, a complement cascade member, complement H factor (CFH), complement factor B (CFB), complement component 2 (C2), complement component 3 (C3), complement component 5 (C5), complement component 5a (C5a), C5b-9, a marker of expression of pro-inflammatory cytokines, TNF, tissue necrosis factor alpha, a marker of angiogenesis and vascular leakage, VEGF, CEP, IL-6, G-CSF, Serum Amyloid A, I CAM-1, Leptin, Glucose, lactose, C-reactive protein, PEDF, PDGF, IFG interferon gamma, interleukin 1-beta, and IL-8.

4. The method of claim 1, wherein the method further comprises determining effectiveness of the therapeutic agent using at least a first diagnostic assay configured to identify the presence or amount of the one or more markers of the eye in the displaced liquid based on the amount of the one or more markers and the period of time.

5. The method of claim 4, wherein the period of time corresponds to a time between a first placement of the therapeutic agent in the reservoir chamber of the implanted therapeutic device and a second placement of a second therapeutic agent in the reservoir chamber of the implanted therapeutic device, the second placement being the injecting of the therapeutic fill volume from the syringe.

6. The method of claim 4, wherein the one or more markers comprises a first marker and a second marker accumulated in the reservoir chamber through the porous structure over the period of time.

7. The method of claim 6, wherein an amount of the first marker and an amount of the second marker are determined using the at least the first diagnostic assay based on an accumulation of time of the first marker and an accumulation of time the second marker.

8. The method of claim 7, wherein the amount of the first marker and the amount of the second marker are determined using the at least the first diagnostic assay based on a parameter corresponding to molecular weight of the first marker and a parameter corresponding to molecular weight of the second marker.

9. The method of claim 4, further comprising determining performance of the implanted therapeutic device implanted in the eye using at least a second diagnostic assay configured to measure the amount of the therapeutic agent in the displaced liquid and the presence or quantity of the one or more non-pharmacologic components in the displaced liquid.

10. The method of claim 9, wherein the one or more non-pharmacologic components comprise one or more of a marker to measure device function, a salt, a surfactant, a stabilizer or a particle.

11. The method of claim 9, wherein the performance of the implanted therapeutic device comprises one or more of a refill efficiency, a rate of release of a therapeutic agent, or a stability of a therapeutic agent.

12. The method of claim 11, further comprising determining stability of a therapeutic agent wherein the stability of the therapeutic agent corresponds to an amount of aggregated therapeutic agent in the displaced liquid.

13. The method of claim 1, wherein the cartridge further comprises an identifier coupled to the container and corresponding to data identifying the container and the patient, wherein the method further comprises receiving the data of the identifier by a processor.

14. The method of claim 1, wherein the container is detachable to release the container from the cartridge.

15. The method of claim 1, wherein the porous vent structure has a resistance to air that is lower than a resistance to liquid of the porous structure of the device preventing release of a therapeutic bolus through the porous structure of the therapeutic device while simultaneously displacing liquid.

16. The method of claim 15, wherein the porous vent structure has a resistance to liquid that is higher than the resistance to liquid of the porous structure of the therapeutic device such that upon wetting of the porous vent structure and further injection of therapeutic fill volume into the reservoir chamber the therapeutic bolus is released through the porous structure of the therapeutic device.