JPWO2020046791A5

JPWO2020046791A5 -

Info

Publication number: JPWO2020046791A5
Application number: JP2021510827A
Authority: JP
Publication date: 2022-09-05

Claims

an intrathecal catheter body having a proximal end, a distal end, a central channel extending between the proximal end and the distal end, and a distal outlet within the distal end;
A tissue engaging portion for the intrathecal catheter to engage patient tissue around an opening therethrough for the intrathecal catheter to protect against leakage of cerebrospinal fluid. a configured tissue engaging portion, the catheter comprising:
said central flow passage including a blocked portion adjacent said distal outlet for creating a venturi effect with fluid being distributed through said distal outlet;
the distal end of the intrathecal catheter fluidly couples the central channel to the exterior of the intrathecal catheter to draw fluid from the exterior of the intrathecal catheter through the distal outlet; A catheter further comprising one or more side channels that provide flow mass amplification to the fluid being dispensed .

said intrathecal catheter further comprising a plurality of radially oriented outlets ; optionally,
wherein said plurality of radially oriented outlets are arranged in a helical configuration along an axial length of said intrathecal catheter; or in a plane perpendicular to said axial length of said intrathecal catheter. or at least one of a plurality of outlets aligned and spaced from one another along the axial length of the intrathecal catheter . catheter .

the distal outlet and the plurality of radially oriented outlets are sized such that a majority of fluid volume dispensed through the intrathecal catheter is distributed through the distal outlet; or 3. The catheter of claim 2 , sized such that a fluid volume dispensed through the intrathecal catheter is dispensed through the distal outlet and the radially directed outlet in substantially equal volumes. catheter .

said intrathecal catheter being radiopaque or above the beginning of said plurality of radially oriented outlets adjacent said distal end or the end of said radially oriented outlets; 4. The catheter of claim 2 or 3 , including radiopaque markings on one or more of the lower portions.

The catheter of any one of claims 1-4 , wherein at least a portion of the intrathecal catheter has a three -layer structure comprising a lumen, a stiffening layer and a skin.

6. The method of claims 1-5 , wherein the distal end of the intrathecal catheter comprises an atraumatic tip with a rounded profile that allows implantation without damaging or exiting the medullary canal. A catheter according to any one of paragraphs.

7. The one or more side channels each extend at a radially inward angle and have an internal opening into the central channel downstream of the closed portion . A catheter according to paragraph 1 .

The distal end of the intrathecal catheter is adapted to allow the cerebrospinal fluid to be drawn through the one or more side channels into the central channel of the catheter to facilitate flow of the fluid through the occlusion. a mixing chamber of said central channel positioned distal to said occlusion portion and said one opening into said mixing chamber configured to merge and create a higher mass flow through said distal outlet; 8. The catheter of claim 7 , further comprising one or more side channel internal openings.

A catheter according to any preceding claim, wherein the distal outlet has a diameter smaller than the inner diameter of the central channel of the intrathecal catheter adjacent to the distal outlet.

a plurality of rings wherein the proximal end of the intrathecal catheter includes reinforcing material that increases the hoop strength of the proximal end, the reinforcing material embedded within the intrathecal catheter proximal end; a coil embedded within said intrathecal catheter proximal end, a polymeric tube embedded within said intrathecal catheter proximal end, or a braided material embedded within said intrathecal catheter proximal end 10. The catheter of any one of claims 1-9 , optionally wherein the stiffening material comprises an external protrusion at the proximal end of the intrathecal catheter , catheter .

A fluid delivery system comprising:
a catheter according to any one of claims 1 to 10;
a port implantable in a subcutaneous location , said port comprising :
a body defining a chamber having an open top and a delivery opening;
a septum disposed on the body, the septum having a lower surface extending across the open top of the chamber and an opposite upper surface;
A cap defining an opening extending therethrough coupled to the body with the opening providing needle access to the septum to secure the septum within the port. a cap configured to: the cap includes a downwardly tapering surface extending around the opening and configured to direct a needle toward the top surface of the septum;
a fluid delivery system comprising: a catheter connection portion;

The catheter connecting portion includes a cylindrical cavity for receiving the proximal end of the catheter, the cylindrical cavity being fluidly coupled with the delivery opening and having an engaging portion, 12. The fluid delivery system of claim 11 , wherein the mating portion comprises one of a threaded portion, a snap fit recess, or a luer lock recess ,
a gasket disposed over the catheter proximal end, the gasket and catheter proximal end configured to be inserted into the cylindrical cavity of the body;
a fastener configured to engage the engagement portion of the cylindrical cavity to compress the gasket and secure the catheter proximal end within the cylindrical cavity. Further comprising a fluid delivery system .

A tissue engaging portion for the intrathecal catheter to engage patient tissue around an opening therethrough for the intrathecal catheter to protect against leakage of cerebrospinal fluid. a configured tissue-engaging portion, said tissue-engaging portion engaging at least one of the patient 's dura or fascia adjacent or within the opening therethrough; 13. The fluid delivery system of claim 11 or 12 , configured to protect against cerebrospinal fluid leakage.

The catheter of any one of claims 1-10 or claims 11-13 , further comprising one or more doses of a nucleic acid, protein therapeutic agent, cell therapeutic agent, small molecule therapeutic agent, or a combination thereof . wherein optionally said protein therapeutic agent, cell therapeutic agent, small molecule therapeutic agent, or combination thereof is used to treat Huntington's disease, spinal muscular atrophy (SMA) , survival motor neuron (SMN) deficiency, amyotrophic lateral sclerosis (ALS), Angelman syndrome, Dravet syndrome, Alzheimer's disease, progressive supranuclear palsy (PSP), frontotemporal dementia (FTD), Parkinson's disease, central nervous system (CNS) lymphoma, pia mater, Friedreich's ataxia, amyloidosis Dutch-type hereditary cerebral hemorrhage (HCHWA-D), cerebral amyloid angiopathy (CAA), amyloid congophilia (ACA), and secondary malignancies (SMN) .

a nucleic acid selected from the group consisting of antisense oligonucleotides, ribozymes, miRNAs, siRNAs, and shRNAs , wherein said nucleic acid is optionally nusinersen, or a clustered regularly spaced short palindromic repeat (CRISPR)-associated protein (Cas) system or a combination thereof, optionally wherein said nucleic acid targets HTT, said nucleic acid comprises a 2'-O-2-methoxyethyl ("2'-MOE") group, or
15. The catheter or fluid delivery system of Claim 14 , wherein said protein therapeutic agent is encoded by one or more doses of a viral vector, optionally said viral vector is an adeno-associated viral vector or an adenoviral vector .