US4838852A — Active specific immune suppression

Claim 1

Independent Claim 80 words

A method for altering the immune system response of a patient to a specific antigen, comprising: (a) artificially introducing the specific antigen into the patient's bloodstream or immune system by injection so as to artificially stimulate said immune system; (b) withdrawing blood cell containing material, including antigen stimulated blood cells, from the patient; (c) treating said material or cells with UV radiation in the presence of a photoactivatable agent; and (d) returning the treated material or cells to the patient.

Claim 2

Independent Claim 80 words

A method for altering the immune system response of a patient to a specific antigen, comprising: (a) artificially introducing the specific antigen into the patient's bloodstream or immune system by injection so as to artificially stimulate said immune system; (b) withdrawing blood cell containing material, including antigen stimulated blood cells, from the patient; (c) treating said material or cells with UV radiation in the presence of a photoactivatable agent; and (d) returning the treated material or cells to the patient.

Claim 3

Dependent Claim 27 words

The method of claim 1, wherein the treating of step (c) comprises mixing the photoactivatable agent with the withdrawn material and irradiating the mixture with UV radiation.

Claim 4

Dependent Claim 18 words

The method of claim 1, wherein the photoactivatable agent is administered to the patient prior to step (b).

Claim 5

Dependent Claim 48 words

The method of claim 1, wherein the treating comprises the steps of: forming said material into an extracorporeal stream, flowing said stream through a treatment chamber substantially transparent to UV radiation and irradiating the stream in the chamber with UV radiation in the presence of the photoactivatable agent.

Claim 6

Dependent Claim 21 words

The method of claim 1, wherein the blood cell containing material is blood, lymph fluid, bone marrow or lymphatic organ tissue.

Claim 7

Dependent Claim 36 words

The method of claim 1, wherein the antigen is associated with a disorder selected from the group consisting of delayed-type hypersensitivity reaction, autoimmune disease, cancer, allergy, infectious disease, rejection of allografts and graft vs. host reaction.

Claim 8

Dependent Claim 11 words

The method of claim 1, wherein the mammal is a human.

Claim 9

Dependent Claim 10 words

The method of claim 1, wherein the cells are lymphocytes.

Claim 10

Dependent Claim 11 words

The method of claim 8, wherein the lymphocytes are T cells.

Claim 11

Dependent Claim 25 words

The method of claim 1, wherein the antigen is a T cell expressing unique T cell receptors which are capable of serving as clonotypic antigens.

Claim 12

Dependent Claim 19 words

The method of claim 6, wherein the disorder is mediated by the clonal expansion of circulating aberrant T cells.

Claim 13

Dependent Claim 12 words

The method of claim 1, wherein the photoactivatable agent is a psoralen.

Claim 14

Dependent Claim 14 words

The method of claim 12, wherein the psoralen is 8-methoxy psoralen or amino-methyl-trimethyl psoralen.

Claim 15

Dependent Claim 28 words

The method of claim 12, wherein the psoralen is present in the blood at a concentration from about 1 nanogram to about 100 micrograms per milliliter of blood.

Claim 16

Dependent Claim 31 words

The method of claim 4, wherein the withdrawing of the material, passage to the treatment station, and return of the material to the patient is carried out as a continuous operation.

Claim 17

Dependent Claim 25 words

The method of claim 15, wherein the flow rate of the extracorporeal stream is in the range of from about 10 to about 75 ml/min.

Claim 18

Dependent Claim 31 words

The method of claim 15, which further comprises separating at least portions of the cells before returning the cells to the patient, by passing the stream through a continuous flow centrifuge.

Claim 19

Dependent Claim 32 words

The method of claim 1, wherein the material is irradiated with photoenergy in the UVA wavelength and at a radiation dose level of from about 0.1 to about 100 joules/cm 2 .

Claim 20

Dependent Claim 20 words

The method of claim 1, wherein the stimulation comprises the formation of certain lymphocytes specifically in response to the antigen.

Claim 21

Dependent Claim 18 words

The method of claim 1, wherein the membrane integrity of the stimulated cells is disrupted in step (c).

Claim 22

Dependent Claim 17 words

The method of claim 1, wherein the DNA within the stimulated cells is altered in step (c).

Claim 23

Independent Claim 110 words

A method for suppressing the immune system response of a patient to a tissue allograft prior to receipt of the allograft, wherein the tissue expresses at least one unique antigen which serves to promote an adverse immunologic response in the patient, comprising: (a) artificially introducing at least one of said antigens into the patient's bloodstream or immune system by injection so as to activate certain lymphocytes which are specifically reactive with said antigen; (b) withdrawing blood cell containing material, including the antigen activated lymphocytes, from the patient; (c) treating said lymphocytes with UV radiation in the presence of a photoactivatable agent; and (d) returning the treated lymphocytes to the patient.

Claim 24

Independent Claim 110 words

A method for suppressing the immune system response of a patient to a tissue allograft prior to receipt of the allograft, wherein the tissue expresses at least one unique antigen which serves to promote an adverse immunologic response in the patient, comprising: (a) artificially introducing at least one of said antigens into the patient's bloodstream or immune system by injection so as to activate certain lymphocytes which are specifically reactive with said antigen; (b) withdrawing blood cell containing material, including the antigen activated lymphocytes, from the patient; (c) treating said lymphocytes with UV radiation in the presence of a photoactivatable agent; and (d) returning the treated lymphocytes to the patient.

Claim 25

Independent Claim 77 words

A method for altering the immune system response of a patient to a specific antigen, comprising: (a) administering the specific antigen to the patient by injection so as to artificially stimulate the patient's immune system; (b) administering a photoactivatable agent to the patient; (c) withdrawing blood cell containing material, including antigen stimulated blood cells, from the patient; (d) treating said material or cells with UV radiation; and (e) returning the treated material or cells to the patient.

Claim 26

Independent Claim 77 words

A method for altering the immune system response of a patient to a specific antigen, comprising: (a) administering the specific antigen to the patient by injection so as to artificially stimulate the patient's immune system; (b) administering a photoactivatable agent to the patient; (c) withdrawing blood cell containing material, including antigen stimulated blood cells, from the patient; (d) treating said material or cells with UV radiation; and (e) returning the treated material or cells to the patient.

Claim 27

Dependent Claim 20 words

The method of claim 23, wherein the antigen is an antigen to which the patient has not been previously exposed.

Claim 28

Dependent Claim 13 words

The method of claim 23, wherein the administering of step (b) is oral.

Annuity Stage	Window Opens	Payment Deadline	Surcharge Period Until	Estimated Fee	Status
3.5 Years (Year 4)	1992-06-12	1992-12-12	1993-06-13	$2000.00	Window Closed / Lapsed
7.5 Years (Year 8)	1996-06-12	1996-12-12	1997-06-13	$3760.00	Window Closed / Lapsed
11.5 Years (Year 12)	2000-06-12	2000-12-12	2001-06-13	$7700.00	Window Closed / Lapsed

Active specific immune suppression

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