Abstract: An apparatus includes a body and a pair of rigid legs extending from the body. The body includes an engagement feature configured to engage a deployment instrument. The legs are parallel with each other. Each leg has a sharp tip. The legs both extend along a plane. The body defines a guide opening. The guide opening is oriented transversely relative to the plane associated with the legs. The guide opening is sized to receive a cannula having a generally flat profile. The guide opening is configured to guide the cannula through a sclerotomy at a substantially tangential orientation.

Abstract: An apparatus for delivering therapeutic agent to an eye comprises a body, a cannula, a hollow needle, and an actuation assembly. The cannula extends distally from the body and is sized and configured to be insertable between a choroid and a sclera of a patient's eye. The actuation assembly is operable to actuate the needle relative to the cannula to thereby drive a distal portion of the needle along an exit axis that is obliquely oriented relative to the longitudinal axis of the cannula. The cannula may be inserted through a sclerotomy incision to position a distal end of the cannula at a posterior region of the eye, between the choroid and sclera. The needle may be advanced through the choroid to deliver the therapeutic agent adjacent to the potential space between the neurosensory retina and the retinal pigment epithelium layer, adjacent to the area of geographic atrophy.

Abstract: An apparatus includes a first member and a second member. The first member is configured to receive a portion of a syringe barrel and includes a first stop surface. The second member includes a second stop surface. Each stop surface is configured to engage the portion of a plunger to thereby arrest longitudinal movement of the plunger relative to the syringe barrel. The second member is operable to move relative to the first member from a first position to a second position. The second member remains coupled with the first member while in both the first position and the second position. The second stop surface engages the portion of the plunger when the second member is in the first position. The second stop surface does not prevent the portion of the plunger from reaching the first stop surface when the second member is in the second position.

Abstract: A method includes inserting a flexible cannula between a sclera and a choroid of an eye. The needle is advanced from a distal end of the flexible cannula, such that the needle pierces the choroid to access a subretinal space of the eye. The needle is used to deliver a first volume of leading bleb fluid to the subretinal space. The delivery of leading bleb fluid is ceased for a duration of time. After expiration of the duration of time, the needle is used to deliver a second volume of the leading bleb fluid to the subretinal space. The combination of the delivered first and second volumes of the leading bleb fluid causes a substantial portion of the retina to detach from the choroid. A therapeutic agent may then be delivered to the subretinal space in the region where the retina is detached from the choroid.

Abstract: An apparatus includes a body, a needle, a catheter, and an actuator assembly. The needle extends distally from the body. The needle has an inner wall defining a needle lumen. The needle lumen is in fluid communication with a fluid port of the body. The catheter is slidably disposed in the needle lumen. The catheter has a catheter lumen. The first actuator assembly is configured to translate the catheter within and relative to the needle. The apparatus may also include an actuator assembly that is configured to rotate the needle relative to the body. The apparatus may be used to first deliver a leading bleb of fluid to the subretinal space in a patient's eye via the needle. The apparatus may then be used to deliver a therapeutic agent to the subretinal space in the patient's eye via the catheter.

Abstract: Aspects of the present invention relate to the recombinant production of a mature complement system protein. Certain embodiments of the present invention relate to recombinant production of fully mature human complement Factor I protein (CFI). Included herein are details of an expression vector with which to recombinantly express fully mature human CFI from mammalian cells. Further disclosed are chromatography steps with which to purify recombinantly expressed CFI. Certain aspects of the present invention relate to the use of an expression system in gene therapy and the like. Certain embodiments of the present invention relate to use of said vector as a medicament, for example for use in the treatment of complement-mediated disorders.

Abstract: The present invention relates to a product comprising (i) an anti-VEGF entity; and (ii) a negative complement regulator, or nucleotide sequences encoding therefor, as a combined preparation for simultaneous, separate or sequential use in therapy. In particular, the anti-VEGF entity is an anti-VEGF antibody, preferably aflibercept and the negative complement regulator is Complement Factor I (CFI) or Complement Factor H Like Protein 1 (FHL1). The main uses are for the treatment of eye diseases, in particular age-related macular degeneration (AMD).

Abstract: An apparatus has a first fluid conduit, a second fluid conduit, a connector member, an first tubular member, a second tubular member, and an inner cannula. The connector member has first and second passageways in which the first and second fluid conduits are positioned, respectively. A portion of the second tubular member is positioned within the lumen of the first tubular member. A proximal portion of the inner cannula is fixedly secured within the lumen of the first tubular member. The inner cannula lumen is in fluid communication with the first and second fluid conduits via the lumen of the first tubular member and the lumen of the second tubular member. The inner cannula may be inserted into the subretinal space of a human eye to deliver a leading bleb of fluid and then deliver a therapeutic agent, without having to withdraw the inner cannula from the subretinal space between the acts of delivering the leading bleb delivering the therapeutic agent.

Abstract: An apparatus for delivering therapeutic agent to an eye comprises a body, a cannula, a hollow needle, and an actuation assembly. The cannula extends distally from the body and is sized and configured to be insertable between a choroid and a sclera of a patient's eye. The actuation assembly is operable to actuate the needle relative to the cannula to thereby drive a distal portion of the needle along an exit axis that is obliquely oriented relative to the longitudinal axis of the cannula. The cannula may be inserted through a sclerotomy incision to position a distal end of the cannula at a posterior region of the eye, between the choroid and sclera. The needle may be advanced through the choroid to deliver the therapeutic agent adjacent to the potential space between the neurosensory retina and the retinal pigment epithelium layer, adjacent to the area of geographic atrophy.

Abstract: A system for storing and delivering a predetermined amount of fluid includes a syringe including a barrel, a flange disposed at the proximal end of the barrel, and a plunger assembly configured to be received in the lumen of the barrel. The plunger assembly includes a piston and a plunger rod. The plunger rod is removably couplable to the piston at the distal end of the plunger rod and includes a thumb press flange at the proximal end of the plunger rod. The system further includes a stop feature that is removably couplable to the syringe or the plunger assembly. The stop feature is configured to arrest distal advancement of the plunger assembly relative to the syringe when the plunger assembly reaches a predetermined position relative to the syringe. The stop thus ensures that a predetermined amount of fluid remains in the barrel.

Abstract: An apparatus includes a body, a cannula, and a needle. The cannula is flexible and extends distally from the body. The needle is slidably disposed in the cannula. The needle includes a sharp distal tip and a curved portion. The needle is configured to translate relative to the cannula between a proximal position and a distal position. The distal tip is configured to be positioned inside the cannula when the needle is in the proximal position. The distal tip is configured to be positioned outside the cannula when the needle is in the distal position. The needle is resiliently biased to extend along a curve through the curved portion.

Abstract: An apparatus includes a body, a cannula, a conduit, and a magnetic element. The cannula extends distally from the body. The cannula is flexible and has a distal end. The cannula defines a lumen distally terminating at the distal end. The cannula is sized and configured to pass between a sclera layer and a choroid layer in a human eye. The conduit is in fluid communication with the lumen. The magnetic element is positioned in the body.

Abstract: An isolated polynucleotide comprising a nucleotide sequence encoding a codon-optimised Complement Factor I (CFI).

Abstract: A product comprising (i) a Complement Factor I (CFI) cofactor; and (ii) Complement Factor I (CFI), or nucleotide sequences encoding therefor, as a combined preparation for simultaneous, separate or sequential use in therapy.

Abstract: A method includes inserting a flexible cannula between a sclera and a choroid of an eye. The needle is advanced from a distal end of the flexible cannula, such that the needle pierces the choroid to access a subretinal space of the eye. The needle is used to aspirate fluid from the subretinal space. The fluid may be present from a retinal detachment, a macular hemorrhage, or other condition present before the procedure begins. The method may further include injecting the fluid in the subretinal space via the needle, in which case the fluid may be a balanced salt solution or other bleb fluid. The method may further include injecting a therapeutic agent into the subretinal space after aspirating the bleb fluid. The volume of injected bleb fluid may be greater than the volume of injected therapeutic agent.

Abstract: An apparatus for delivering therapeutic agent to an eye comprises a body, a cannula, a hollow needle, and an actuation assembly. The cannula extends distally from the body and is sized and configured to be insertable between a choroid and a sclera of a patient's eye. The actuation assembly is operable to actuate the needle relative to the cannula to thereby drive a distal portion of the needle along an exit axis that is obliquely oriented relative to the longitudinal axis of the cannula. The cannula may be inserted through a sclerotomy incision to position a distal end of the cannula at a posterior region of the eye, between the choroid and sclera. The needle may be advanced through the choroid to deliver the therapeutic agent adjacent to the potential space between the neurosensory retina and the retinal pigment epithelium layer, adjacent to the area of geographic atrophy.

Abstract: An apparatus includes a body and a pair of rigid legs extending from the body. The body includes an engagement feature configured to engage a deployment instrument. The legs are parallel with each other. Each leg has a sharp tip. The legs both extend along a plane. The body defines a guide opening. The guide opening is oriented transversely relative to the plane associated with the legs. The guide opening is sized to receive a cannula having a generally flat profile. The guide opening is configured to guide the cannula through a sclerotomy at a substantially tangential orientation.

Abstract: An apparatus includes a body, a needle, a catheter, and an actuator assembly. The needle extends distally from the body. The needle has an inner wall defining a needle lumen. The needle lumen is in fluid communication with a fluid port of the body. The catheter is slidably disposed in the needle lumen. The catheter has a catheter lumen. The first actuator assembly is configured to translate the catheter within and relative to the needle. The apparatus may also include an actuator assembly that is configured to rotate the needle relative to the body. The apparatus may be used to first deliver a leading bleb of fluid to the subretinal space in a patient's eye via the needle. The apparatus may then be used to deliver a therapeutic agent to the subretinal space in the patient's eye via the catheter.

Abstract: An apparatus includes a pad assembly, an injector assembly, an injector driver, and a fluid source. The pad assembly is sized and configured to be placed on a forehead of a patient. The injector assembly includes a body, a flexible cannula, and a needle. The body is configured to be removably secured to the pad assembly. The cannula is sized to be inserted through an incision in an eye of a patient. The needle is slidably disposed in the cannula. The injector driver is operable to drive the needle longitudinally relative to the flexible cannula. The fluid source assembly is in fluid communication with the needle.

Abstract: An apparatus includes a pad assembly, an injector assembly, an injector driver, and a fluid source. The pad assembly is sized and configured to be placed on a forehead of a patient. The injector assembly includes a body, a flexible cannula, and a needle. The body is configured to be removably secured to the pad assembly. The cannula is sized to be inserted through an incision in an eye of a patient. The needle is slidably disposed in the cannula. The injector driver is operable to drive the needle longitudinally relative to the flexible cannula. The fluid source assembly is in fluid communication with the needle.