# US 7,611,831 B2 · Adsorbing pathogen-inactivating compounds with porous particles immobilized in a matrix

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- Number: US 7,611,831 B2
- Document ID: US7611831B2
- Status: Granted
- Kind: B2
- Application number: 11/243,822
- Filed: 2005-10-04
- Published: 2006-05-04
- Granted: 2009-11-03
- Earliest claimed: 1998-01-06
- Assignees: Cerus Corporation
- Inventors: Derek J. Hei
- Web page: https://patentgrep.com/patent/US7611831B2

## CPC

- A61M 1/3679: {by absorption (A61M1/3675 takes precedence)}
- A01N 1/124: Disinfecting agents, e.g. antimicrobials
- A01N 1/128: Chemically defined matrices for immobilising, holding or storing living parts, e.g. alginate gels; Chemically altering living parts, e.g. by cross-linking
- A61K 35/18: Erythrocytes (haemoglobin A61K38/42)
- A61L 2/00: Disinfection or sterilisation of materials or objects, in general; Accessories therefor
- A61L 2/16: using chemical substances
- A61M 1/0209: {Multiple bag systems for separating or storing blood components}
- A61M 1/0218: {with filters}
- A61M 1/3616: {Batch-type treatment}
- A61M 1/3686: {by removing photoactive agents after irradiation}
- B01J 20/20: comprising free carbon; comprising carbon obtained by carbonising processes
- B01J 20/26: Synthetic macromolecular compounds
- B01J 20/261: {obtained by reactions only involving carbon to carbon unsaturated bonds (macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds per se C08F)}
- B01J 20/28004: {Sorbent size or size distribution, e.g. particle size}
- B01J 20/28014: {characterised by their form}
- B01J 20/28019: {Spherical, ellipsoidal or cylindrical}
- B01J 20/28026: {Particles within, immobilised, dispersed, entrapped in or on a matrix, e.g. a resin}
- B01J 20/28028: {Particles immobilised within fibres or filaments}
- B01J 20/28057: {Surface area, e.g. B.E.T specific surface area}
- B01J 20/28064: {being in the range 500-1000 m2/g}
- B01J 20/28066: {being more than 1000 m2/g}
- B01J 20/28078: {Pore diameter}
- B01J 20/28083: {being in the range 2-50 nm, i.e. mesopores}
- B01J 20/28085: {being more than 50 nm, i.e. macropores}
- C07D 219/10: attached in position 9
- C07D 405/12: linked by a chain containing hetero atoms as chain links
- C07D 493/04: Ortho-condensed systems
- C07F 9/64: Acridine or hydrogenated acridine ring systems
- A61L 2103/05: Living organisms or biological materials
- A61L 2103/09: Blood or products thereof
- A61M: DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY (introducing media into or onto the bodies of animals A61D7/00; means for inserting tampons A61F13/26; devices for administering food or medicines orally A61J; containers for collecting, storing or administering blood or medical fluids A61J1/05); DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY (surgery A61B; chemical aspects of surgical articles A61L); DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR {(Electrotherapy, e.g. producing anaesthesia by the use of alternating or intermittent currents A61N1/36021)}
- A01N: PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF (preservation of food or foodstuff A23); BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES (preparations for medical, dental or toiletry purposes which kill or prevent the growth or proliferation of unwanted organisms A61K); PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61L: METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES (preservation of bodies or disinfecting characterised by the agents employed A01N; preserving, e.g. sterilising, food or foodstuffs A23; preparations for medical, dental or toiletry purposes A61K)
- B01J: CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- C07F: ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM (metal-containing porphyrins C07D487/22)

## Abstract

Methods and devices are provided for reducing the concentration of low molecular weight compounds in a biological composition containing cells while substantially maintaining a desired biological activity of the biological composition. The device comprises highly porous adsorbent particles, and the adsorbent particles are immobilized by an inert matrix. The matrix containing the particles is contained in a housing, and the particles range in diameter from about 100 μm to about 1500 μm. The device can be used to adsorb and remove a pathogen-inactivating compounds from a biological composition such as a blood product.

## Claims

### Claim 1

A pathogen-inactivating compound adsorption system for reducing the concentration of a low molecular weight pathogen-inactivating compound in an aqueous biological composition containing cellular elements, wherein the pathogen-inactivating compound adsorption system comprises a housing compatible with the biological composition containing an adsorption medium comprising porous adsorbent particles immobilized within a sintered matrix formed from polymeric particulate material, wherein the diameter of the adsorbent particles ranges from about 100 μm to about 1500 μm, wherein the adsorbent particles have an affinity for said pathogen-inactivating compound, wherein the system is configured to remove said pathogen-inactivating compound from said biological composition in a batch process, and wherein the system is configured so that the cellular elements in the biological composition treated with the system maintain sufficient biological activity so that said biological composition is suitable for infusion within a human.

### Claim 2 (depends on 1)

A system according to claim 1, wherein the porous adsorbent particles have a surface area greater than about 750 m2/g, and the porous adsorbent particles are between 25 and 85 percent of the weight of the adsorption medium.

### Claim 3 (depends on 2)

A system according to claim 2, wherein the porous adsorbent particles are between 50 and 80 percent of the weight of the adsorption medium, and the adsorption medium has a particle loading of between 100 and 500 g/m2.

### Claim 4 (depends on 3)

A system according to claim 3, wherein the adsorption medium has a particle loading of between 250 and 350 g/m2.

### Claim 5 (depends on 1)

A system according to claim 1, wherein the matrix contains said porous adsorbent particles.

### Claim 6 (depends on 5)

A system according to claim 5, wherein the porous adsorbent particles comprise a synthetic polymeric adsorbent having a porous network structure and having a surface area greater than about 750 m2/g.

### Claim 7 (depends on 5)

A system according to claim 5, wherein the porous adsorbent particles comprise activated carbon.

### Claim 8 (depends on 6)

A system according to claim 6, wherein the porous adsorbent particles comprise a polyaromatic resin.

### Claim 9 (depends on 8)

A system according to claim 8, wherein said resin has a pore size between about 25 and 800 Å.

### Claim 10 (depends on 9)

A system according to claim 9, wherein said resin has a pore size between about 25 and 150 Å.

### Claim 11 (depends on 10)

A system according to claim 10, wherein said resin has a pore size between about 25 and 50 Å.

### Claim 12 (depends on 6)

A system according to claim 6, wherein the porous adsorbent particles do not require prewetting before use.

### Claim 13 (depends on 6)

A system according to claim 6, wherein the porous adsorbent particles comprise a hypercrosslinked resin.

### Claim 14 (depends on 7)

A system according to claim 7, wherein the porous adsorbent particles comprise activated carbon having a surface area between about 1000 and 3000 m2/g.

### Claim 15 (depends on 14)

A system according to claim 14, wherein the activated carbon is derived from a synthetic source and at least about 50% of pores of the activated carbon particles have a diameter less than about 20 Å.

### Claim 16 (depends on 6)

A system according to claim 6, wherein the diameter of the porous adsorbent particles is between about 300 and 900 μm.

### Claim 17 (depends on 7)

A system according to claim 7, wherein the diameter of the porous adsorbent particles is between about 300 and 900 μm.

### Claim 18 (depends on 1)

A system according to claim 1 wherein the pathogen inactivating compound comprises a nucleic acid-binding compound.

### Claim 19 (depends on 18)

A system according to claim 18, wherein the nucleic acid-binding compound comprises a psoralen derivative.

### Claim 20 (depends on 18)

A system according to claim 18, wherein the nucleic acid-binding compound comprises an acridine derivative.

### Claim 21 (depends on 18)

A system according to claim 18, wherein the nucleic acid-binding compound comprises a dye.

### Claim 22 (depends on 18)

A system according to claim 18, wherein the nucleic acid-binding compound has an electrophilic group or a group capable of forming an electrophilic group.

### Claim 23 (depends on 22)

A system according to claim 22, wherein the porous adsorbent particles additionally have an affinity for a quencher.

### Claim 24 (depends on 18)

A system according to claim 18, wherein the porous adsorbent particles additionally have an affinity for a degradation product of said nucleic acid-binding compound.

### Claim 25 (depends on 1, 13)

A system according to claim 1 or claim 13, wherein the adsorbent particles have an internal surface area between about 300 and 1100 m2/g.

### Claim 26 (depends on 1, 5)

A system according to claim 1, or claim 5 wherein the porous adsorbent particles comprise macroreticular adsorbent particles possessing both macropores and micropores.

### Claim 27 (depends on 18)

A method for reducing the concentration of a low molecular weight compound in a biological composition containing cellular elements, wherein said low molecular weight compound comprises a nucleic acid-binding compound and wherein said method comprises treating the biological composition with a system of claim 18 for between about 0.5 hour and 5 weeks to adsorb the low molecular weight compound onto the porous adsorbent particles of the system and reduce the concentration of the low molecular weight compound in the biological composition, wherein the cellular elements in the biological composition treated with the system maintain sufficient biological activity so that said biological composition is suitable for infusion within a human.

### Claim 28 (depends on 27)

A method according to claim 27, wherein the nucleic acid-binding compound adsorbed onto the porous adsorbent particles of the system comprises an acridine derivative.

### Claim 29 (depends on 27)

A method according to claim 27, wherein the nucleic acid-binding compound adsorbed onto the porous adsorbent particles of the system comprises a dye.

### Claim 30 (depends on 27)

A method according to claim 27, wherein the biological composition contacts the porous adsorbent particles and the matrix at a temperature of about 22° C. for between about 0.5 hour and seven days.

### Claim 31 (depends on 30)

A method according to claim 30, wherein the biological composition comprises platelets.

### Claim 32 (depends on 30)

A method according to claim 30, wherein the biological composition contacts the porous adsorbent particles and the matrix at a temperature of about 22° C. for between about 0.5 and about 36 hours.

### Claim 33 (depends on 32)

A method according to claim 32, wherein the biological composition is treated with the system at a temperature of about 22° C. for between about 0.5 and about 24 hours.

### Claim 34 (depends on 32)

A method according to claim 32, wherein the biological composition is treated with the system at a temperature of about 22° C. for between about 0.5 and about 12 hours.

### Claim 35 (depends on 33)

A method according to claim 33 and further comprising subsequently reducing the temperature of the biological composition and the system to 4° C. and contacting the biological composition with the adsorbent particles and the matrix at a temperature of about 4° C.

### Claim 36 (depends on 35)

A method according to claim 35, wherein said biological composition contacts the adsorbent particles for at a temperature of about 4° C. for up to 5 weeks.

### Claim 37 (depends on 35)

A method according to claim 35, wherein said biological composition comprises red blood cells.

### Claim 38 (depends on 27)

A method according to claim 27, wherein the biological composition comprises a blood product.

### Claim 39 (depends on 28)

A method according to claim 28, wherein the biological composition comprises a blood product.

### Claim 40 (depends on 29)

A method according to claim 29, wherein the biological composition comprises a blood product.

### Claim 41 (depends on 30)

A method according to claim 30, wherein the biological composition comprises a blood product.

### Claim 42 (depends on 32)

A method according to claim 32, wherein the biological composition comprises a blood product.

### Claim 43 (depends on 33)

A method according to claim 33, wherein the biological composition comprises a blood product.

### Claim 44 (depends on 34)

A method according to claim 34, wherein the biological composition comprises a blood product.

### Claim 45 (depends on 35)

A method according to claim 35, wherein the biological composition comprises a blood product.

### Claim 46 (depends on 36)

A method according to claim 36, wherein the biological composition comprises a blood product.

### Claim 47 (depends on 28)

A method according to claim 28, wherein the acridine derivative comprises 5-[(β-carboxyethyl)amino]acridine.

### Claim 48 (depends on 18)

A method for reducing the concentration of a low molecular weight compound in a biological composition containing cellular elements, wherein said low molecular weight compound comprises a psoralen nucleic acid-binding compound and wherein said method comprises treating the biological composition with a system of claim 18 for between about 0.5 hour and 5 weeks to adsorb the low molecular weight compound onto the porous adsorbent particles of the system and reduce the concentration of the low molecular weight compound in the biological composition, wherein the cellular elements in the biological composition treated with the system maintain sufficient biological activity so that said biological composition is suitable for infusion within a human.

### Claim 49 (depends on 48)

A method according to claim 48, wherein no more than about ten percent of an amount of said psoralen nucleic acid-binding compound originally added to said biological composition remains as free psoralen in said biological composition.

### Claim 50 (depends on 48)

A method according to claim 48, wherein said psoralen nucleic acid-binding compound is selected from the group consisting of 4′-(4-amino-2-oxa)butyl-4,5′,8-trimethyl psoralen, 8-methoxypsoralen, halogenated psoralens, isopsoralens and psoralens linked to quaternary amines, 5′-bromomethyl-4,4 ′,8-trimethylpsoralen, 4′-bromomethyl-4,5′,8-trimethylpsoralen, 4′-(4-amino-2-aza)butyl-4,5′,8-trimethylpsoralen, 4′-(2-aminoethyl)-4,5′,8-trimethylpsoralen, 4′-(5-amino-2-oxa)pentyl-4,5′,8-trimethylpsoralen, 4′-(5-amino-2-aza)pentyl-4,5′,8-trimethylpsoralen, 4′-(6-amino-2-aza)hexyl-4,5′,8-trimethylpsoralen, 4′-(7-amino-2,5-oxa)heptyl-4,5′,8-trimethylpsoralen, 4′-(12-amino-8-aza-2,5-dioxa)dodecyl-4,5′,8-trimethylpsoralen, 4′-(13-amino-2-aza-6,11-dioxa)tridecyl-4,5′,8-trimethylpsoralen, 4′-(7-amino-2-aza)heptyl-4,5′,8-trimethylpsoralen, 4′-(7-amino-2-aza-5-oxa)heptyl-4,5′,8-trimethylpsoralen, 4′-(9-amino-2,6-diaza)nonyl-4,5′,8-trimethylpsoralen, 4′-(8-amino-5-aza-2-oxa)octyl-4,5′,8-trimethylpsoralen, 4′-(9-amino-5 -aza-2-oxa)nonyl-4,5′,8-trimethylpsoralen, 4′-(14-amino-2,6,11-triaza)tetradecyl-4,5′,8-trimethylpsoralen, 5′-(4-amino-2-aza)butyl-4,4′,8-trimethylpsoralen, 5′-(6-amino-2-aza)hexyl-4,4′,8-trimethylpsoralen and 5′-(4-amino-2-oxa)butyl-4,4′,8-trimethylpsoralen.

### Claim 51 (depends on 48)

A method according to claim 48, wherein the biological composition comprises a blood product.

### Claim 52 (depends on 49)

A method according to claim 49, wherein the biological composition comprises a blood product.

### Claim 53 (depends on 50)

A method according to claim 50, wherein the biological composition comprises a blood product.

### Claim 54 (depends on 27, 48)

A method according to claim 27 or claim 48 wherein the biological composition containing said cellular elements after contacting the porous adsorbent particles has higher yield of cells over a comparable method in which said porous adsorbent particles are not immobilized.

### Claim 55 (depends on 27, 48)

A method according to claim 27 or claim 48 wherein the biological composition containing said cellular elements after contacting the porous adsorbent particles has improved performance in an in vitro assay over a comparable method in which said porous adsorbent particles are not immobilized.

### Claim 56

A pathogen-inactivating compound adsorption system for reducing the concentration of a low molecular weight pathogen-inactivating compound in a biological composition, wherein the pathogen-inactivating compound adsorption system comprises a housing compatible with the biological composition and containing an adsorption medium comprising adsorbent particles having a network pore structure immobilized within a sintered matrix formed from polymeric particulate material, wherein the diameter of the adsorbent particles ranges from about 1 μm to about 200 μm, wherein the adsorbent particles have an affinity for said pathogen-inactivating compound, wherein the system is configured to remove said pathogen-inactivating compound from said biological composition in a flow process, wherein the system is configured so that the biological composition treated with the system maintains sufficient biological activity so that said biological composition is suitable for infusion within a human, the system further comprising a particle retention medium downstream of the adsorption medium, wherein said particle retention medium retains particles shed from said adsorption medium.