United States Patent 5,624,963 is a foundational GelTex patent covering nonabsorbed, crosslinked polymeric bile-acid sequestrants, including polymer structures associated with colesevelam hydrochloride. Its broadest claims cover therapeutic use, polymer compositions, and post-polymer alkylation with hydrophobic and ammonium-containing groups. The patent issued April 29, 1997 and, based on its pre-June 8, 1995 filing date, expired approximately April 29, 2014. It no longer presents a U.S. patent-barrier risk, but it remains important for understanding the historical patent estate surrounding Welchol and colesevelam.

United States Drug Patent 5,624,963: Scope, Claims, Expiration, and Bile-Acid Sequestrant Patent Landscape

What does United States Patent 5,624,963 cover?

US 5,624,963 covers polymeric materials that remove bile salts from the gastrointestinal tract through ion exchange. The patent is directed to a platform rather than a narrowly defined small-molecule active ingredient.

The claimed technology combines:

A crosslinked polymer backbone.
Ion-exchangeable functional groups.
Hydrophobic comonomers that promote interaction with bile acids.
Optional amine comonomers.
Optional quaternary ammonium functionality.
Optional exchangeable counterions.
Optional alkylation of the polymer after crosslinking.
Oral administration to remove bile salts from a patient.

The patent’s commercial relevance arises from the similarity between these claimed materials and colesevelam hydrochloride, the active polymer in Welchol.

The patent does not claim a conventional molecularly discrete compound. It claims broad classes of polymer compositions defined by repeat units, comonomers, degrees of crosslinking, ion-exchange groups, and alkylating agents.

Who owns US 5,624,963 and what are its key patent dates?

Event	Date or status
Earliest priority date	December 23, 1993
U.S. filing	Before June 8, 1995
Patent issued	April 29, 1997
Patent number	US 5,624,963
Original technology owner	GelTex Pharmaceuticals, Inc.
Historical product association	Colesevelam hydrochloride and Welchol
Estimated U.S. expiration	April 29, 2014
Current enforceability	Expired
Patent term extension relevant to this patent	None identified in the cited public records

Because the application was filed before June 8, 1995, the patent was generally governed by the former 17-year term from issuance rather than the 20-year term from the earliest effective nonprovisional filing date. The resulting ordinary expiration date was approximately April 29, 2014, subject to any applicable patent-term adjustment, disclaimer, or fee history.

The patent’s expiration is more important than its original breadth for current freedom-to-operate analysis. A third party cannot now be sued in the United States for practicing the expired claims.

How many independent claims does US 5,624,963 have?

The patent contains eight apparent independent claim groups:

Claim	Claim category	Principal subject matter
1	Method	Administering crosslinked polymers to remove bile salts
17	Method	Administering a second class of crosslinked polymer
24	Composition	Therapeutic composition containing the first polymer class
25	Composition	Therapeutic composition containing the second polymer class
26	Polymer composition	Crosslinked polymer with hydrophobic comonomer
42	Method	Administering an alkylated reaction product
58	Composition	Therapeutic composition containing an alkylated polymer
59	Polymer composition	Alkylated polymer composition

Claims 2-16 depend principally from claim 1. Claims 18-23 depend from claim 17. Claims 27-41 depend from claim 26. Claims 43-57 depend from claim 42. Claims 60-74 depend from claim 59.

The issued claim text supplied for claims 9-12 contains apparent dependency errors. For example, claim 9 refers to claim 11, and claim 10 also appears to depend on claim 11. Those references likely reflect transcription or issued-document drafting defects. The controlling analysis must use the official issued patent and its prosecution history, not a reformatted claim transcription.

What are the broadest claim limitations?

Claims 1 and 17: therapeutic-use claims

Claims 1 and 17 require a method for removing bile salts from a patient by ion exchange. The method requires administering a therapeutically effective amount of one or more crosslinked polymers.

The key limitations are:

The material must be a polymer.
The polymer must be crosslinked.
The polymer must contain one of the specified repeat-unit classes.
The polymer must remove bile salts through ion exchange.
The polymer must be non-toxic and stable after ingestion.
The material must be administered to a patient in a therapeutically effective amount.

Claim 1 adds a monoreactive hydrophobic comonomer as a required component. Claim 17 is structurally different and does not expressly require that hydrophobic comonomer in the independent claim, although dependent claim 20 adds it.

These claims are method claims, not product-by-process claims. During the patent term, infringement would have turned on the administered polymer’s structure and its use for bile-acid removal, rather than solely on the manufacturer’s synthesis route.

Claims 24 and 25: therapeutic compositions

Claims 24 and 25 cover therapeutic compositions containing the polymer classes described in claims 1 and 17. These claims shift the focus from the act of administration to the composition itself.

The composition claims require:

A therapeutic amount of polymer.
A defined repeat-unit structure.
Crosslinking.
Non-toxic and ingestion-stable characteristics.

The claims do not appear to require a particular tablet, powder, suspension, capsule, dose strength, excipient, or release profile. This creates broad formulation coverage, but the claims remain limited by the polymer’s structural definitions.

Claims 26 and 59: composition-level platform claims

Claim 26 covers a crosslinked polymer containing:

A monoreactive hydrophobic comonomer; and
A specified ion-exchange repeat unit.

Claim 59 covers the reaction product of a crosslinked polymer and at least one alkylating agent.

These claims are commercially significant because they can reach the polymer before it is formulated as a drug product. Claim 59 is particularly relevant to polymers prepared by functionalizing an amine-containing crosslinked backbone after polymerization.

What polymer structures are protected?

The claim set covers multiple structural families. The structural drawings in the patent define the exact attachment points and ionic groups, but the claims can be grouped functionally as follows:

Structural feature	Claim coverage
Crosslinked ion-exchange polymer	Claims 1-3, 17-19, 26-28, 42-44, 59-61
Hydrophobic comonomer	Claims 1, 4, 8, 20, 21, 26, 29, 33, 36, 39
Amine comonomer	Claims 5 and 6; claims 30 and 31
Quaternary ammonium comonomer	Claims 9, 12, 34, 37
Exchangeable counterions	Claims 15, 16, 40, 41, 48, 49, 65, 66
Alkylated polymer	Claims 42, 50-57, 58, 67-74
Therapeutic use for bile salts	Claims 1, 17, 42
Therapeutic composition	Claims 24, 25, 58
Polymer composition without express therapeutic-use limitation	Claims 26 and 59

The hydrophobic comonomer Markush group is unusually broad. It includes styrene derivatives, vinyl naphthalene derivatives, vinylbiphenyls, viny anisoles, aminostyrenes, acrylamides, methacrylamides, acrylates, methacrylates, and fluorinated analogues.

The claims specifically identify examples such as:

n-Butylmethacrylamide.
Hexafluorobutyl methacrylate.
Heptadecafluorodecyl methacrylate.
Styrene.
2-Vinylnaphthalene.
Vinyl pyridine.
Vinyl imidazole.
4-Vinylbiphenyl.
4-Vinylanisole.
4-Aminostyrene.
Isopropylacrylamide.
Hexafluoroisopropyl acrylate.

What crosslinking levels are protected?

Claims 2, 3, 18, 19, 27, 28, 43, 44, 60, and 61 define the amount of multifunctional crosslinking comonomer.

Limitation	Claimed range
Broad crosslinking range	About 0.5% to 25% by weight
Narrower preferred range	About 1% to 10% by weight

These limitations provide fallback positions within the broader polymer claims. A polymer outside the stated ranges would not automatically avoid infringement of every independent claim, because some independent claims do not expressly recite a crosslinker percentage. The ranges are most relevant to the dependent claims and to assessing literal claim coverage.

The functional purpose of crosslinking is to produce an insoluble, orally stable material that remains in the gastrointestinal tract rather than being absorbed systemically.

How does the alkylation claim group relate to colesevelam?

Claims 42 and 59 cover a crosslinked polymer that is reacted with one or more alkylating agents. The alkylating agent is broadly defined as an RX compound in which:

R is a C1-C20 alkyl, hydroxyalkyl, aralkyl, alkylammonium, or alkylamido group; and
X is an electrophilic leaving group.

The listed leaving groups include:

Halides.
Epoxides.
Tosylates.
Mesylates.

Claims 50-57 and 67-74 narrow the alkylation chemistry to combinations such as:

C1-C20 alkyl halides.
Alkyl halide ammonium salts.
Dihaloalkanes.
Hydroxyalkyl halides.
Aralkyl halides.
Epoxyalkyl ammonium salts.
Epoxyalkylamides.
Combinations of hydrophobic alkylating agents and alkylammonium agents.
Combinations of alkyl and hydroxyalkyl agents.

This claim group maps closely to the design logic of colesevelam: an insoluble crosslinked polymer modified with hydrophobic groups and positively charged ammonium functionality. The commercial polymer is designed to bind negatively charged bile acids through a combination of ionic attraction and hydrophobic interaction.

The expired claims cannot block current manufacture of colesevelam or an equivalent polymer in the United States. They remain relevant as prior art and as evidence of the technical lineage of later polymeric bile-acid sequestrant filings.

What is the Orange Book status of US 5,624,963?

US 5,624,963 was historically associated with the Welchol and colesevelam patent estate, but current Orange Book significance is limited by expiration.

The FDA Orange Book lists patents submitted by an NDA holder for a drug product. For a polymeric drug such as colesevelam hydrochloride, the relevant listings may include composition, formulation, manufacturing, or method-of-use patents. An Orange Book listing does not extend an expired patent term and does not independently establish infringement.

For current commercial analysis:

Issue	Assessment
Historical Orange Book relevance	High
Current blocking effect	None after expiration
Current Paragraph IV value	None against this patent
Current 30-month stay potential	None based solely on this patent
Relevance to generic colesevelam	Historical foundational patent only

The commercial protection for Welchol after 2014 depended on other unexpired patents, regulatory exclusivity, market position, manufacturing know-how, and litigation or settlement positions. US 5,624,963 itself is no longer an enforceable Orange Book barrier.

When did colesevelam lose U.S. exclusivity?

Colesevelam lost protection in stages rather than on one date.

Protection type	Approximate status
Original composition and platform patents	Expired by approximately 2014
NDA regulatory exclusivity	Expired years earlier
Later formulation or product patents	Depended on individual patent expiration dates
Generic entry	Became possible after relevant blocking patents and regulatory barriers expired
Current status	Generic colesevelam hydrochloride products are available or have been approved through the ANDA pathway

Welchol was approved by FDA in 2000 for reducing elevated low-density lipoprotein cholesterol. It later received an indication for glycemic control in adults with type 2 diabetes. The drug is a nonabsorbed polymeric bile-acid sequestrant rather than a biologic, so biosimilar approval rules do not apply. Generic competition proceeds through ANDAs, with pharmaceutical-equivalence and bioequivalence issues handled under the FDA’s framework for locally acting or nonabsorbed products.

Which companies challenged or competed with the Welchol estate?

The competitive field includes both pharmacologic alternatives and generic versions of colesevelam.

Product	Active material	Company or historical sponsor	Patent position
Welchol	Colesevelam hydrochloride	GelTex, later marketed by Daiichi Sankyo	Original platform estate expired
Questran	Cholestyramine	Bristol-Myers Squibb and other sponsors	Legacy resin technology; core patents expired
Prevalite	Cholestyramine	Multiple sponsors	Genericized bile-acid sequestrant
Colestid	Colestipol hydrochloride	Pfizer and other sponsors	Legacy polymer technology; core patents expired
Generic colesevelam	Colesevelam hydrochloride	Multiple ANDA applicants	Competes after relevant patent barriers

Cholestyramine and colestipol are older resin products with different polymer architectures. They do not generally practice the same colesevelam-specific claim strategy, although all occupy the bile-acid sequestrant category.

The key competitive distinction is tolerability and dosing. Colesevelam was developed to improve gastrointestinal tolerability and reduce some of the formulation and palatability problems associated with older resins. Its patent value therefore rested on both the polymer chemistry and the ability to commercialize a practical oral dosage form.

What patent litigation and Paragraph IV risks affected US 5,624,963?

A Paragraph IV certification against an expired patent has no practical litigation effect. The relevant questions during the patent’s life were whether a generic applicant’s polymer:

Contained the claimed repeat units.
Used a crosslinked architecture within the claims.
Included a listed hydrophobic comonomer or equivalent.
Had amine or quaternary ammonium functionality.
Was prepared through one of the claimed alkylation routes.
Was intended for bile-acid sequestration.
Fell within the claim’s counterion and composition limitations.

Potential validity challenges would have focused on:

Written description for the very broad Markush classes.
Enablement across the large number of monomers and alkylating agents.
Obviousness over earlier ion-exchange resins and bile-acid sequestrants.
Definiteness of polymer structures and undefined variables.
Claim dependency and typographical defects.
Whether particular polymers satisfied the “non-toxic and stable once ingested” limitations.

The claims have breadth, but they also contain multiple structural and functional restrictions. A generic manufacturer could have pursued a design-around using a different backbone, different charge-bearing group, a non-listed hydrophobic functionality, a different post-polymerization modification, or a formulation that did not meet the claimed composition requirements. Those strategies would have required claim-by-claim analysis during the patent term.

No current Paragraph IV risk attaches to US 5,624,963 because the patent has expired.

How strong was the patent estate for colesevelam?

Historically, the estate was strong at the platform level but less absolute than a single-compound patent.

Strengths

Broad coverage of crosslinked, orally stable bile-acid sequestrant polymers.
Separate method, therapeutic-composition, and polymer-composition claim categories.
Coverage of both copolymer design and post-polymerization alkylation.
Broad lists of hydrophobic comonomers.
Coverage of counterions and quaternary ammonium modifications.
Claims directed to the therapeutic use of removing bile salts.

Weaknesses

The patent did not claim one sharply defined chemical entity.
Polymer claim scope depends on interpreting structural repeat units.
Broad Markush language creates written-description and enablement exposure.
Functional limitations such as non-toxicity and ingestion stability can complicate infringement proof.
Several claim dependencies in the supplied text are internally inconsistent.
Alternative polymer architectures could potentially avoid literal coverage.
The patent’s effective commercial life ended in 2014.

The patent was therefore valuable as an early platform patent, but its long-term exclusivity depended on continuation patents, later product claims, regulatory protection, and manufacturing control.

What manufacturing and intellectual-property barriers remain after expiration?

Expiration of US 5,624,963 removes its legal exclusivity but does not eliminate all barriers to commercial entry.

Manufacturing barriers

A generic manufacturer still must reproduce or qualify:

Polymer particle-size distribution.
Crosslink density.
Substitution level.
Quaternary ammonium content.
Hydrophobic group content.
Counterion composition.
Residual monomer and reagent limits.
Extractables and leachables.
Microbial and elemental impurity specifications.
Batch-to-batch binding capacity.
Tablet compression and dissolution properties.

For a nonabsorbed polymer, conventional plasma bioequivalence may be insufficient to characterize product performance. FDA may examine comparative in vitro binding, physicochemical properties, clinical pharmacology, or other product-specific evidence.

Intellectual-property barriers

Potential remaining barriers historically included:

Later formulation patents.
Tablet or dosage-form patents.
Manufacturing-process patents.
Combination-use patents.
Pediatric-use patents.
Labeling-related method-of-use patents.
Regulatory exclusivity.
Trade secrets involving polymer functionalization and particle engineering.

Those rights must be separated from US 5,624,963. Expiration of this patent does not establish that every later colesevelam patent has expired.

How does US 5,624,963 compare with older bile-acid sequestrant patents?

Criterion	US 5,624,963	Cholestyramine estate	Colestipol estate
Technology	Synthetic crosslinked functional polymer	Quaternized styrene-divinylbenzene resin	Crosslinked amine polymer
Claim strategy	Platform Markush claims plus alkylation	Resin composition and use	Polymer composition and use
Commercial product	Colesevelam	Questran, Prevalite	Colestid
Hydrophobic modification	Expressly emphasized	More inherent in resin architecture	Less central to the modern claim strategy
Post-polymerization alkylation	Expressly claimed	Not the principal distinguishing feature	Not the principal distinguishing feature
Current core patent barrier	Expired	Expired	Expired
Generic pathway	ANDA	ANDA	ANDA

US 5,624,963 is more technically expansive than the legacy resin patents because it claims a family of polymer backbones, hydrophobic comonomers, charged groups, counterions, and alkylation reactions.

What is the current commercial risk from US 5,624,963?

The current direct patent risk is zero because the patent is expired. The commercial relevance is historical and analytical.

For investors and business-development teams, the patent indicates:

Colesevelam was protected through a polymer platform rather than a conventional active-ingredient patent.
Generic entry risk was ultimately driven by expiry of the foundational polymer claims and later Welchol patents.
The technology is not subject to biosimilar competition because colesevelam is a synthetic polymer.
Current competition is primarily generic colesevelam and older bile-acid sequestrants.
Manufacturing know-how remains relevant even without enforceable exclusivity.
Any current freedom-to-operate review must examine later patents, not rely on US 5,624,963 alone.

Key Takeaways

US 5,624,963 covers crosslinked polymeric bile-acid sequestrants, including broad classes of hydrophobic and charged polymers.
The patent contains eight apparent independent claim groups spanning methods, therapeutic compositions, polymer compositions, and alkylated reaction products.
Its most commercially relevant concepts are crosslinked polyamine polymers modified with hydrophobic and ammonium-containing groups.
The patent issued April 29, 1997 and expired approximately April 29, 2014.
It is historically associated with GelTex’s colesevelam technology and the Welchol product.
It is no longer an enforceable U.S. barrier and cannot support a current Paragraph IV litigation stay.
Colesevelam is a synthetic polymer drug, so biosimilar rules do not apply.
Generic entry proceeds through the ANDA pathway and depends on later patents, FDA requirements, and manufacturing capability.
The patent’s broad Markush scope was balanced by structural, crosslinking, functional, and therapeutic-use limitations.
Current freedom-to-operate analysis must focus on later colesevelam formulation, manufacturing, dosage-form, and method-of-use patents.

FAQs About US 5,624,963 and Colesevelam Patent Protection

Is US 5,624,963 still enforceable?

No. The patent expired approximately April 29, 2014 based on its issue date and pre-June 8, 1995 filing status.

Does US 5,624,963 claim colesevelam by name?

No. It claims structural and functional classes of polymers. Colesevelam may fall within relevant claim categories, but the patent does not depend on the product name.

Can a generic manufacturer rely on expiration of US 5,624,963?

Yes, but only as to this patent. A generic manufacturer must separately evaluate later patents listed for Welchol or colesevelam hydrochloride.

Is colesevelam a biologic requiring a biosimilar?

No. Colesevelam hydrochloride is a synthetic, nonabsorbed polymer. Generic products use the ANDA pathway rather than the biosimilar pathway.

What is the main technical barrier to making generic colesevelam?

The principal barrier is reproducing the polymer’s physicochemical profile, including crosslinking, substitution, particle properties, bile-acid binding, impurity control, and dosage-form performance.

References

U.S. Patent No. 5,624,963. (1997). Bile acid sequestrants. U.S. Patent and Trademark Office.
U.S. Food and Drug Administration. (2000). Welchol (colesevelam hydrochloride) prescribing information. FDA.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations. FDA.
U.S. Food and Drug Administration. (2024). Orange Book: Approved drug products with therapeutic equivalence evaluations. FDA.
U.S. Patent and Trademark Office. (2024). Patent term calculator and patent term examination guidance. USPTO.
GelTex Pharmaceuticals, Inc. (1997). Bile acid sequestrants. U.S. Patent and Trademark Office patent record.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	0764174	⤷ Start Trial	91100	Luxembourg	⤷ Start Trial
European Patent Office	0764174	⤷ Start Trial	300159	Netherlands	⤷ Start Trial
European Patent Office	0764174	⤷ Start Trial	CA 2004 00027	Denmark	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 5,624,963

Summary for Patent: 5,624,963