	US 12,312,574 B2
	Polymer-coated crosslinked alginate gel fiber
Shoji Furusako, Tokyo (JP); Tsutomu Satoh, Tokyo (JP); Tomohiro Narumi, Tokyo (JP); and Shingo Sato, Tokyo (JP)
Assigned to MOCHIDA PHARMACEUTICAL CO., LTD., Tokyo (JP)
Filed by MOCHIDA PHARMACEUTICAL CO., LTD., Tokyo (JP)
Filed on Dec. 21, 2023, as Appl. No. 18/392,583.
Application 18/392,583 is a continuation of application No. PCT/JP2022/024935, filed on Jun. 22, 2022.
Claims priority of application No. 2021-104094 (JP), filed on Jun. 23, 2021; and application No. PCT/JP2021/048567 (WO), filed on Dec. 27, 2021.
Prior Publication US 2024/0174959 A1, May 30, 2024
Int. Cl. C12M 1/12 (2006.01); C08L 5/04 (2006.01); C12M 1/00 (2006.01); C12N 5/071 (2010.01); C12N 11/04 (2006.01)

CPC C12M 25/10 (2013.01) [C08L 5/04 (2013.01); C12M 23/20 (2013.01); C12N 5/0676 (2013.01); C12N 5/0682 (2013.01); C12N 11/04 (2013.01)]

20 Claims

1. A polymer-coated crosslinked alginate gel fiber consisting of:

a core layer; and

a cationic polymer layer, wherein the cationic polymer layer is selected from the group consisting of poly-L-ornithine (PLO), polymethylene-CO-guanidine (PMCG), polyallylamine (PAA), and polyethyleneimine,

wherein the core layer comprises an antibody-producing cell or a bioactive substance-producing cell embedded in crosslinked alginate gel that is obtained by performing a crosslinking reaction using chemically modified alginic acid derivatives represented by Formula (I) and Formula (II), and

the cationic polymer layer coats the surface of the core layer,

wherein the polymer-coated crosslinked alginate gel fiber has a length within a range of 0.01 to 100 m and is suitable for use in the production of at least one member selected from the group consisting of an antibody and a bioactive substance, and

wherein the chemically modified alginic acid derivative represented by Formula (I) is a chemically modified alginic acid derivative represented by Formula (I) below:

in Formula (I), (ALG) represents alginic acid; —NHCO— represents an amide bond through an arbitrary carboxyl group of the alginic acid; wherein Akn represents a cyclic alkyne group; -L¹- is a divalent linker that bonds to the cyclic alkyne group (Akn), Akn-L¹- is a group selected from the group consisting of the partial structural formulae shown in the following table, wherein in each formula, the right side of the broken line is not included:


No.	Akn—L¹—

ALK- 1a		x1a = 1-6

ALK- 1b		x1b = 1-6 y1b = 1-6

ALK- 2		x2 = 1-6 y2 = 0-6 z2 = 1-6

ALK- 3a		x3a = 1-6 y3a = 0-6 z3a = 2-6

ALK- 3b		x3b = 1-6 y3b = 0-6 z3b = 1-6

ALK- 4		x4 = 1-6 y4 = 2-6

ALK- 5a		x5a = 1-6 y5a = 2-6 z5a = 2-6

ALK- 5b		x5b = 1-6 y5b = 1-6 z5b = 2-6

TABLE 72-2

No.	Akn—L¹—

ALK- 6		x6 = 1-6 y6 = 1-6 z6 = 2-6

ALK- 7a		x7a = 1-6 y7a = 2-6 z7a = 2-6 v7a = 1-6

ALK- 7b		x7b = 1-6 y7b = 1-6 z7b = 2-6 v7b = 1-6

and

the chemically modified alginic acid derivative represented by Formula (II) is a chemically modified alginic acid derivative represented by Formula (II) below:

in Formula (II), (ALG) represents alginic acid; —NHCO— represents an amide bond through an arbitrary carboxyl group of the alginic acid; -L²- represents a linker selected from the group consisting of partial structural formulae, wherein in each formula, the outsides of the broken lines at both ends are not included, shown in the following table:


No.	—L²—

LN- 1		a1 = 2-6 b1 = 2-6

LN- 2		a2 = 2-6 b2 = 1-6

LN- 3		a3 = 1-6 b3 = 1-6

LN- 4		a4 = 1-6 b4 = 2-6

LN- 5		a5 = 1-6

LN- 6		a6 = 2-6.