# US 11,439,761 B2 · Cell delivery system and methods of operation thereof

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- Number: US 11,439,761 B2
- Document ID: US11439761B2
- Status: Granted
- Kind: B2
- Application number: 16/437,206
- Filed: 2019-06-11
- Published: 2019-09-26
- Granted: 2022-09-13
- Earliest claimed: 2016-12-28
- Assignees: SanBio, Inc.
- Applicants: SanBio, Inc.
- Inventors: Michael McGrogan
- Web page: https://patentgrep.com/patent/US11439761B2

## CPC

- A61M 5/31531: {Microsyringes, e.g. having piston bore diameter close or equal to needle shaft diameter}
- A61K 35/28: Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
- A61M 5/1782: {Devices aiding filling of syringes in situ (combination of a vial and a syringe for transferring or mixing their contents A61J1/2096, filling of medical containers in general B65B3/003)}
- A61M 5/3129: {Syringe barrels (A61M5/3205, A61M5/50 take precedence)}
- A61M 5/315: Pistons; Piston-rods; Guiding, blocking or restricting the movement of the rod {or piston}; Appliances on the rod for facilitating dosing {; Dosing mechanisms}
- A61M 5/32: Needles; Details of needles pertaining to their connection with syringe or hub (infusion needles A61M5/158); Accessories for bringing the needle into, or holding the needle on, the body; Devices for protection of needles
- A61M 5/36: with means for eliminating or preventing injection or infusion of air into body (dialysis systems, blood oxygenators A61M1/14; haemofiltration equipment A61M1/34; {automatic tube cut-off A61M39/281})
- A61M 2202/09: Body tissue
- A61M 2209/045: for filling, e.g. for filling reservoirs
- A61M 2209/088: on the body
- A61M 2210/0693: Brain, cerebrum
- A61M: DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY (introducing media into or onto the bodies of animals A61D7/00; means for inserting tampons A61F13/26; devices for administering food or medicines orally A61J; containers for collecting, storing or administering blood or medical fluids A61J1/05); DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY (surgery A61B; chemical aspects of surgical articles A61L); DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR {(Electrotherapy, e.g. producing anaesthesia by the use of alternating or intermittent currents A61N1/36021)}
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)

## Abstract

A method of preparing a syringe in connection with a therapeutic treatment is disclosed. The method can include removing a plunger of the syringe from a barrel of the syringe, aligning the barrel in a horizontal orientation, filling a lumen of the barrel with a viscous material through an opening at a proximal end of the barrel, and inserting a plunger tip into the lumen to seal the lumen. The method can also include attaching an implantation device to a hub coupled to the barrel at a distal end of the barrel. The method can also include depressing the plunger until the cell suspension fills the implantation device and a droplet of the cell suspension is expelled from a distal tip of the implantation device.

## Claims

### Claim 1

A method of implanting a viscous material into a subject in connection with a therapeutic treatment, the method comprising:
removing a plunger of a syringe from a barrel of the syringe, wherein the barrel has a proximal end, a distal end, and a lumen in between the proximal end and the distal end;
filling at least part of the lumen with the viscous material through an opening at the proximal end and reinserting the plunger;
coupling a needle or a cannula to the distal end of the barrel of the syringe;
injecting the viscous material into the subject using the syringe at one or more deposit sites; and
rotating the syringe about a longitudinal axis of the syringe after each injection.

### Claim 2 (depends on 1)

The method of claim 1, wherein, for injections at more than one deposit site, the method further comprises rotating the syringe about a longitudinal axis of the syringe after each injection.

### Claim 3 (depends on 1)

The method of claim 1, further comprising aligning the barrel in a horizontal orientation prior to filling at least part of the lumen with the viscous material.

### Claim 4 (depends on 1)

The method of claim 1, further comprising depressing the plunger until the viscous material fills the needle coupled to the syringe at the distal end of the barrel and a droplet of the viscous material is expelled from the needle through a needle tip and discarded prior to injecting the viscous material.

### Claim 5 (depends on 1)

The method of claim 1, wherein the injecting of the viscous material comprises injecting at least 20 μL of the viscous material at each of five deposit sites in the subject at an injection rate of at least 10 μL per minute.

### Claim 6 (depends on 1)

The method of claim 1, further comprising placing the syringe into a stereotactic frame prior to injecting the viscous material.

### Claim 7 (depends on 1)

The method of claim 1, further comprising measuring a volume of the viscous material injected using a meniscus of the viscous material remaining in the barrel.

### Claim 8 (depends on 1)

The method of claim 1, wherein the therapeutic treatment comprises at least one of treatment of a traumatic brain injury, treatment of ischemic damage, treatment of retinal degeneration, and treatment of a neurodegenerative disease.

### Claim 9 (depends on 1)

The method of claim 1, wherein the viscous material is a cell suspension.

### Claim 10 (depends on 9)

The method of claim 9, wherein the cell suspension comprises cells descendant from mesenchymal stem cells transiently-transfected by a polynucleotide encoding a Notch intracellular domain.

### Claim 11

A method of treating a subject with cells, the method comprising:
removing a plunger of a syringe from a barrel of the syringe, wherein the barrel has a proximal end, a distal end, and a lumen in between the proximal end and the distal end;
filling at least part of the lumen with the cells through an opening at the proximal end and reinserting the plunger;
coupling an implantation device to the syringe at the distal end of the barrel;
injecting an amount of the cells into the subject using the syringe and the implantation device at a first deposit site in the subject;
rotating at least one of the syringe and the implantation device about a longitudinal axis; and
injecting another amount of the cells into the subject using the syringe and the implantation device at a second deposit site in the subject.

### Claim 12 (depends on 11)

The method of claim 11, further comprising aligning the barrel in a horizontal orientation prior to filling at least part of the lumen with the cells.

### Claim 13 (depends on 11)

The method of claim 11, further comprising depressing the plunger until the cells fill the implantation device and a droplet of the cells is expelled from the implantation device through a distal tip of the implantation device and discarded prior to injecting the cells.

### Claim 14 (depends on 11)

The method of claim 11, further comprising retracting at least one of the syringe and the implantation device a predetermined distance subsequent to injecting at the first deposit site and prior to injecting the cells at the second deposit site.

### Claim 15 (depends on 14)

The method of claim 14, wherein the predetermined distance is between 1 mm and 10 mm, and wherein at least one of the first deposit site and the second deposit site is in the brain of the subject.

### Claim 16 (depends on 11)

The method of claim 11, further comprising placing the implantation device into a stabilization cannula prior to injecting the cells.

### Claim 17 (depends on 11)

The method of claim 11, further comprising measuring an amount of the cells injected using a meniscus of the cells remaining in the barrel.

### Claim 18 (depends on 11)

The method of claim 11, wherein filling at least part of the lumen comprises inserting a pipette tip of a micropipette into the lumen of the barrel through an opening at the proximal end when the barrel is aligned in the horizontal orientation and injecting the cells into the lumen using the micropipette.

### Claim 19 (depends on 11)

The method of claim 11, wherein the amount of the cells injected at each deposit site is 20 μL.

### Claim 20 (depends on 11)

The method of claim 11, wherein the cells comprise cells descendant from mesenchymal stem cells transiently-transfected by a polynucleotide encoding a Notch intracellular domain.

### Claim 21 (depends on 11)

The method of claim 11, wherein the implantation device is at least one of a cannula and a needle.

### Claim 22 (depends on 11)

The method of claim 11, wherein the implantation device is a cannula, wherein the cannula comprises a proximal end and a distal end, wherein the proximal end comprises a cannula hub, wherein the cannula hub comprises a cannula extension that is in fluid communication with the lumen of the cannula and that protrudes from the cannula hub so that it extends into the lumen of the syringe at a distal end of the syringe.
