Production of aldehyde-treated allergen-containing substances

Claim 2

A process for producing an aldehyde-treated allergen of low allergenic reactivity in allergic humans and which retains the desired immunizing properties of the native allergen leading to amelioration of the symptomatology of allergic individuals and concomitant production of blocking antibody considered to be associated with, but not necessarily uniquely responsible for, such relief of symptoms, and which is capable of inducing in mammals the formation of blocking antibodies against the native allergen in significant concentration which comprises allowing allergens from which essentially all low molecular weight, non-allergenic substances have been removed to react chemically under mild conditions with an aldehyde solution selected from the group consisting of formaldehyde, lower saturated aliphatic di-functional aldehydes and combinations thereof, in at least two steps with the provisos that any formaldehyde reactions are carried out in a non-phenolic environment and wherein said mild conditions comprise a reaction step which is carried out at a temperature of from just above the freezing point of the solution to 15° C., and at least one subsequent step which is carried out at a temperature of from about 25° C. to 40° C., with any combination of formaldehyde, said dialdehyde or mixture thereof in each of the successive steps, to form a product having intra- or inter-molecular crosslinking induced by said aldehydes and the allergenic determinant groups are modified to result in substantial reduction of allergenic properties while largely retaining the desired immunizing properties.

Claim 3

The process of claim 1 wherein the aldehyde in all steps is formaldehyde.

Claim 4

The process of claim 1 wherein the aldehyde in all steps is a dialdehyde having the formula: ##STR3## wherein n is an integer of from 1 to about 6.

Claim 5

The process of claim 1 wherein the aldehyde in all steps is glutaraldehyde.

Claim 6

The process of claim 1 wherein the aldehyde is a combination of formaldehyde and dialdehydes utilized as a mixture in each step.

Claim 7

The process of claim 1 wherein the aldehyde is a combination of formaldehyde and glutaraldehyde utilized as a mixture in each step.

Claim 8

The process of claim 1 wherein the allergens are allowed to react with said aldehyde in two steps.

Claim 9

A process of claim 1 wherein there is present along with said aldehyde solution at least one additive selected from the group consisting of 1,4-diaminobutane, lysine, ornithine, 1,5-diamino-pimelic acid, arginine, adipamide, aspartic acid, serine and alanine.

Claim 10

The process of claim 1 wherein the allergen-containing material is an aqueous extract of a pollen substance.

Claim 11

The process of claim 1 wherein the allergen-containing material is an aqueous extract of a grass pollen substance.

Claim 12

The process of claim 1 wherein the allergen-containing material contains a Group I grass pollen allergen preparation.

Claim 13

The process of claim 1 wherein the allergen-containing material is an aqueous extract of a weed pollen substance.

Claim 14

The process of claim 1 wherein the allergen-containing material is an aqueous extract of a tree pollen substance.

Claim 15

The process of claim 1 wherein the allergen-containing material contains ragweed pollen's Antigen E.

Claim 16

The process of claim 1 wherein the allergen-containing material is an aqueous extract selected from the group consisting of those containing house dust mites, house dust mite residues and mixtures thereof.

Claim 17

The process of claim 1 wherein the allergen-containing material is an aqueous extract of a member selected from the group consisting of a fungus and mixtures of fungi.

Claim 18

The process of claim 1 wherein the allergen-containing material is an aqueous extract of a member selected from the group consisting of an insect, an insect product, and mixtures thereof.

Claim 19

The process of claim 1 wherein the allergen-containing material is an aqueous extract of a member selected from the group consisting of animal dander, animal skin, animal hair and mixtures thereof.

Claim 20

The process of claim 1 wherein the allergen-containing material is an aqueous extract of food allergen.

Claim 21

The product of the process of claim 1.

Claim 22

The product of the process of claim 2.

Claim 23

The product of the process of claim 3.

Claim 24

The product of the process of claim 4.

Claim 25

The product of the process of claim 5.

Claim 26

The product of the process of claim 6.

Claim 27

The product of the process of claim 7.

Claim 28

The product of the process of claim 8.

Claim 29

The product of the process of claim 9.

Claim 30

The product of the process of claim 10.

Claim 31

The product of the process of claim 11.

Claim 32

The product of the process of claim 12.

Claim 33

The product of the process of claim 13.

Claim 34

The product of the process of claim 14.

Claim 35

The product of the process of claim 15.

Claim 36

The product of the process of claim 16.

Claim 37

The product of the process of claim 17.

Claim 38

The product of the process of claim 18.

Claim 39

The product of the process of claim 19.

Claim 40

A process for producing an aldehyde-treated allergen of low allergenic reactivity in allergic humans and which retains the desired immunizing properties of the native allergen leading to amelioration of the symptomatology of allergic individuals and concomitant production of blocking antibody considered to be associated with, but not necessarily uniquely responsible for, such relief of symptoms, and which is capable of inducing in mammals the formation of blocking antibodies against the native allergen in significant concentration, which comprises allowing allergens from which essentially all low molecular weight, non-allergenic substances have been removed to react chemically under mild conditions with a solution of formaldehyde in at least two steps, said formaldehyde reactions being carried out in a non-phenolic environment, and wherein said mild conditions comprise a reaction step which is carried out using a formaldehyde concentration of about 0.5 M to 2.5 M at a temperature of from just above the freezing point of the solution to 15° C., and at least one subsequent step which is carried out using a formaldehyde concentration of about 0.36 M to 0.5 M at a temperature of from about 25° C. to 40° C., to form a product having intra- or inter-molecular crosslinking induced by said formaldehyde and the allergenic determinant groups are modified to result in substantial reduction of allergenic properties while largely retaining the desired immunizing properties of the native allergen.

Claim 41

A process for producing an aldehyde-treated allergen of low allergenic reactivity in allergic humans and which retains the desired immunizing properties of the native allergen leading to amelioration of the symptomatology of allergic individuals and concomitant production of blocking antibody considered to be associated with, but not necessarily uniquely responsible for, such relief of symptoms, and which is capable of inducing in mammals the formation of blocking antibodies against the native allergen in significant concentration, which comprises allowing allergens from which essentially all low molecular weight, non-allergenic substances have been removed to react chemically under mild conditions with a solution of formaldehyde in at least two steps, said formaldehyde reactions being carried out in a non-phenolic environment, and wherein said mild conditions comprise a reaction step which is carried out using a formaldehyde concentration of about 0.5 M to 2.5 M at a temperature of from just above the freezing point of the solution to 15° C., and at least one subsequent step which is carried out using a formaldehyde concentration of about 0.36 M to 0.5 M at a temperature of from about 25° C. to 40° C., to form a product having intra- or inter-molecular crosslinking induced by said formaldehyde and the allergenic determinant groups are modified to result in substantial reduction of allergenic properties while largely retaining the desired immunizing properties of the native allergen.

Claim 42

The product of the process of claim 39.

Claim 43

A process for producing an aldehyde-treated allergen of low allergenic reactivity in allergic humans and which retains the desired immunizing properties of the native allergen leading to amelioration of the symptomatology of allergic individuals and concomitant production of blocking antibody considered to be associated with, but not necessarily uniquely responsible for, such relief of symptoms, and which is capable of inducing in mammals the formation of blocking antibodies against the native allergen in significant concentration, which comprises allowing allergens from which essentially all low molecular weight, non-allergenic substances have been removed to react chemically under mild conditions with a solution of lower saturated aliphatic di-functional aldehydes in at least two steps, wherein said mild conditions comprise a reaction step which is carried out using a difunctional aldehyde concentration of about 0.01 M to 0.1 M at a temperature of from just above the freezing point of the solution to 15° C., and at least one subsequent step which is carried out using a difunctional aldehyde concentration of about 0.01 M to 0.1 M at a temperature of from about 25° C. to 40° C., to form a product having intra- or inter-molecular crosslinking induced by said aldehydes and the allergenic determinant groups are modified to result in substantial reduction of allergenic properties while largely retaining the desired immunizing properties of the native allergen.

Claim 44

A process for producing an aldehyde-treated allergen of low allergenic reactivity in allergic humans and which retains the desired immunizing properties of the native allergen leading to amelioration of the symptomatology of allergic individuals and concomitant production of blocking antibody considered to be associated with, but not necessarily uniquely responsible for, such relief of symptoms, and which is capable of inducing in mammals the formation of blocking antibodies against the native allergen in significant concentration, which comprises allowing allergens from which essentially all low molecular weight, non-allergenic substances have been removed to react chemically under mild conditions with a solution of lower saturated aliphatic di-functional aldehydes in at least two steps, wherein said mild conditions comprise a reaction step which is carried out using a difunctional aldehyde concentration of about 0.01 M to 0.1 M at a temperature of from just above the freezing point of the solution to 15° C., and at least one subsequent step which is carried out using a difunctional aldehyde concentration of about 0.01 M to 0.1 M at a temperature of from about 25° C. to 40° C., to form a product having intra- or inter-molecular crosslinking induced by said aldehydes and the allergenic determinant groups are modified to result in substantial reduction of allergenic properties while largely retaining the desired immunizing properties of the native allergen.

Claim 45

The product of the process of claim 41.

Claim 46

A process for producing an aldehyde-treated allergen of low allergenic reactivity in allergic humans and which retains the desired immunizing properties of the native allergen leading to amelioration of the symptomatology of allergic individuals and concomitant production of blocking antibody considered to be associated with, but not necessarily uniquely responsible for, such relief of symptoms, and which is capable of inducing in mammals the formation of blocking antibodies against the native allergen in significant concentration, which comprises allowing allergens from which essentially all low molecular weight, non-allergenic substances have been removed to react chemically under mild conditions with a solution of an aldehyde in at least two steps comprising a formaldehyde reaction step which is carried out in a non-phenolic environment under mild conditions using a formaldehyde concentration of about 0.5 M to 2.5 M at a temperature of from just above the freezing point of the solution to 15° C., and at least one subsequent step which is carried out using a lower saturated aliphatic difunctional aldehyde concentration of about 0.01 M to 0.1 M at a temperature of from about 25° C. to 40° C., to form a product having intra- or inter-molecular crosslinking induced by said aldehydes and the allergenic determinant groups are modified to result in substantial reduction of allergenic properties while largely retaining the desired immunizing properties of the native allergen.

Claim 47

A process for producing an aldehyde-treated allergen of low allergenic reactivity in allergic humans and which retains the desired immunizing properties of the native allergen leading to amelioration of the symptomatology of allergic individuals and concomitant production of blocking antibody considered to be associated with, but not necessarily uniquely responsible for, such relief of symptoms, and which is capable of inducing in mammals the formation of blocking antibodies against the native allergen in significant concentration, which comprises allowing allergens from which essentially all low molecular weight, non-allergenic substances have been removed to react chemically under mild conditions with a solution of an aldehyde in at least two steps comprising a formaldehyde reaction step which is carried out in a non-phenolic environment under mild conditions using a formaldehyde concentration of about 0.5 M to 2.5 M at a temperature of from just above the freezing point of the solution to 15° C., and at least one subsequent step which is carried out using a lower saturated aliphatic difunctional aldehyde concentration of about 0.01 M to 0.1 M at a temperature of from about 25° C. to 40° C., to form a product having intra- or inter-molecular crosslinking induced by said aldehydes and the allergenic determinant groups are modified to result in substantial reduction of allergenic properties while largely retaining the desired immunizing properties of the native allergen.

Claim 48

The product of the process of claim 43.

Claim 49

A process for producing an aldehyde-treated allergen of low allergenic reactivity in allergic humans and which retains the desired immunizing properties of the native allergen leading to amelioration of the symptomatology of allergic individuals and concomitant production of blocking antibody considered to be associated with, but not necessarily uniquely responsible for, such relief of symptoms, and which is capable of inducing in mammals the formation of blocking antibodies against the native allergen in significant concentration, which comprises allowing allergens from which essentially all low molecular weight, non-allergenic substances have been removed to react chemically under mild conditions with a solution of an aldehyde in at least two steps comprising a difunctional aldehyde reaction step which is carried out under mild conditions using a lower saturated aliphatic difunctional aldehyde concentration of about 0.01 M to 0.1 M at a temperature of from just above the freezing point of the solution to 15° C., and at least one subsequent step which is carried out in a non-phenolic environment using a formaldehyde concentration of about 0.36 M to 0.5 M at a temperature of from about 25° C. to 40° C., to form a product having intra- or inter-molecular crosslinking induced by said formaldehyde and the allergenic determinant groups are modified to result in substantial reduction of allergenic properties while largely retaining the desired immunizing properties of the native allergen.

Claim 50

A process for producing an aldehyde-treated allergen of low allergenic reactivity in allergic humans and which retains the desired immunizing properties of the native allergen leading to amelioration of the symptomatology of allergic individuals and concomitant production of blocking antibody considered to be associated with, but not necessarily uniquely responsible for, such relief of symptoms, and which is capable of inducing in mammals the formation of blocking antibodies against the native allergen in significant concentration, which comprises allowing allergens from which essentially all low molecular weight, non-allergenic substances have been removed to react chemically under mild conditions with a solution of an aldehyde in at least two steps comprising a difunctional aldehyde reaction step which is carried out under mild conditions using a lower saturated aliphatic difunctional aldehyde concentration of about 0.01 M to 0.1 M at a temperature of from just above the freezing point of the solution to 15° C., and at least one subsequent step which is carried out in a non-phenolic environment using a formaldehyde concentration of about 0.36 M to 0.5 M at a temperature of from about 25° C. to 40° C., to form a product having intra- or inter-molecular crosslinking induced by said formaldehyde and the allergenic determinant groups are modified to result in substantial reduction of allergenic properties while largely retaining the desired immunizing properties of the native allergen.

Claim 51

The product of the process of claim 45.

Claim 52

A process for producing an aldehyde-treated allergen of low allergenic reactivity in allergic humans and which retains the desired immunizing properties of the native allergen leading to amelioration of the symptomatology of allergic individuals and concomitant production of blocking antibody considered to be associated with, but not necessarily uniquely responsible for, such relief of symptoms, and which is capable of inducing in mammals the formation of blocking antibodies against the native allergen in significant concentration, which comprises allowing allergens from which essentially all low molecular weight, non-allergenic substances have been removed to react chemically under mild conditions with a solution of an aldehyde in at least two steps, said aldehyde reactions being carried out in a non-phenolic environment, and wherein said mild conditions comprise a reaction step which is carried out using an aldehyde mixture containing a formaldehyde concentration of about 0.36 M to 0.5 M and a lower saturated aliphatic difunctional aldehyde concentration of 0.01 M to 0.1 M at a temperature of from just above the freezing point of the solution to 15° C., and at least one subsequent step which is carried out using a formaldehyde concentration of about 0.06 M to 1.0 M and a lower saturated aliphatic difunctional aldehyde concentration of 0.01 M to 0.1 M at a temperature of from about 25° C. to 40° C., to form a product having intra- or inter-molecular crosslinking induced by said formaldehyde and the allergenic determinant groups are modified to result in substantial reduction of allergenic properties while largely retaining the desired immunizing properties of the native allergen.

Claim 53

A process for producing an aldehyde-treated allergen of low allergenic reactivity in allergic humans and which retains the desired immunizing properties of the native allergen leading to amelioration of the symptomatology of allergic individuals and concomitant production of blocking antibody considered to be associated with, but not necessarily uniquely responsible for, such relief of symptoms, and which is capable of inducing in mammals the formation of blocking antibodies against the native allergen in significant concentration, which comprises allowing allergens from which essentially all low molecular weight, non-allergenic substances have been removed to react chemically under mild conditions with a solution of an aldehyde in at least two steps, said aldehyde reactions being carried out in a non-phenolic environment, and wherein said mild conditions comprise a reaction step which is carried out using an aldehyde mixture containing a formaldehyde concentration of about 0.36 M to 0.5 M and a lower saturated aliphatic difunctional aldehyde concentration of 0.01 M to 0.1 M at a temperature of from just above the freezing point of the solution to 15° C., and at least one subsequent step which is carried out using a formaldehyde concentration of about 0.06 M to 1.0 M and a lower saturated aliphatic difunctional aldehyde concentration of 0.01 M to 0.1 M at a temperature of from about 25° C. to 40° C., to form a product having intra- or inter-molecular crosslinking induced by said formaldehyde and the allergenic determinant groups are modified to result in substantial reduction of allergenic properties while largely retaining the desired immunizing properties of the native allergen.

Claim 54

The product of the process of claim 47.