United States Drug Patent RE42152: Scope, Claims, Expiration, Orange Book Status and HIV Drug Patent Landscape

U.S. Patent RE42,152 is an expired reissue patent covering bis-macrocyclic polyamine compounds, pharmaceutical compositions containing them, and selected metal complexes with anti-HIV activity. Its commercially important compound is plerixafor, also known as AMD3100, the active ingredient in Mozobil. The patent’s broadest composition claim is directed to two identical nitrogen-containing macrocycles connected through a methylene-substituted aromatic or heteroaromatic linker.

RE42,152 expired on December 10, 2013, based on the 17-year term of the original U.S. Patent No. 5,583,131. The reissue did not restart or extend the original patent term. It therefore presents no current patent barrier to an abbreviated new drug application, generic launch, licensing transaction, or freedom-to-operate position involving plerixafor, subject to other unexpired patents and regulatory exclusivities.

What patent is U.S. RE42152 and what does it cover?

RE42,152 is titled “Bis-macrocyclic compounds, and pharmaceutical compositions containing them.” It is a reissue of U.S. Patent No. 5,583,131. The patent claims both compositions and specific chemical compounds.

The central structural concept is:

Z-R-A-R′-Y

where:

Z and Y are identical cyclic polyamine groups;
each macrocycle has 10 to 15 ring members;
each macrocycle has 3 to 6 ring amine nitrogens;
the ring nitrogens are separated by at least two carbon atoms;
the macrocycles contain no ring heteroatoms other than nitrogen;
R and R′ are methylene groups attached to ring nitrogen atoms; and
A is an aromatic or heteroaromatic linker, excluding quinoline under claim 1 as supplied.

The most commercially significant embodiment is the para-phenylene-linked bicyclam:

1,1′-[1,4-phenylenebis(methylene)]-bis-1,4,8,11-tetraazacyclotetradecane

This compound is plerixafor, commonly administered as the hydrochloride salt. Its principal pharmacology is CXCR4 antagonism. Mozobil is approved for hematopoietic stem-cell mobilization, not as an HIV treatment, although the patent claims anti-HIV compositions based on the original discovery program. [1, 2]

How broad is claim 1 of RE42152?

Claim 1 is a genus claim covering pharmaceutical compositions containing a defined class of linked cyclic polyamines.

Its practical scope has four principal boundaries:

Claim element	Scope
Macrocycle size	10 to 15 ring members
Number of ring nitrogens	3 to 6
Macrocycle identity	Z and Y must be identical
Linker	Methylene groups connecting macrocycles to an aromatic or heteroaromatic A group
Ring heteroatoms	Nitrogen only
Nitrogen substitution	Ring amines otherwise unsubstituted
Pharmaceutical form	Active compound with a pharmaceutically acceptable diluent or carrier
Biological limitation	Active against HIV

The claim is broader than plerixafor because it is not limited to a 14-member ring, four nitrogens, or a para-phenylene linker. It reaches multiple macrocycle sizes, linker geometries, heteroaromatic systems, and selected polyamine arrangements.

The claim is narrower than a generic “bis-polyamine” claim because both macrocycles must be identical and must satisfy the specified ring-size and nitrogen-spacing requirements. A compound using different macrocycles on each side of the linker would fall outside the literal requirement that Z and Y be identical.

What compounds are specifically claimed by RE42152?

Claim 2 narrows the macrocycles to 14-member rings containing four ring nitrogens. This limitation describes the tetraazacyclotetradecane class that includes plerixafor.

The claims identify the following compound families:

Compound family	Representative claim coverage
Meta-phenylene bicyclam	Claims 3, 36 and related claims
Para-phenylene bicyclam	Claims 4, 37 and related claims
Biphenylene-linked bicyclam	Claims 7, 24 and 38
Alternative tetraazacyclotetradecane isomer	Claims 8 and 39
Pyridine-linked bicyclams	Claims 10, 11, 25, 26 and 40, 41
Thiophene-linked bicyclam	Claims 12, 27 and 42
Bipyridine-linked bicyclam	Claims 13, 28 and 43
Phenanthroline-linked bicyclam	Claims 14, 29 and 44
Tetraazacyclotetradecane isomers	Claims 15, 16, 30, 31, 45 and 46
Triazacyclododecane compounds	Claims 21, 22, 51 and 52
Substituted phenylene compounds	Claims 17-20 and 32-35, among others
Metal complexes	Claims 5, 6 and 23

The claim set includes acid addition salts, zinc complexes, copper complexes, and compositions containing the relevant active compounds.

Which claims cover plerixafor and Mozobil?

Plerixafor is most directly represented by the para-phenylene-linked tetraazacyclotetradecane compound:

1,1′-[1,4-phenylenebis(methylene)]-bis-1,4,8,11-tetraazacyclotetradecane

The relevant claims are:

Claim 4, directed to the compound in acid addition salt form;
Claim 37, directed to a pharmaceutical composition containing the compound;
Claim 2, to the extent the compound satisfies the 14-member, four-nitrogen macrocycle limitation;
Claim 1, as the broader composition genus; and
Related compound and composition claims covering the same bicyclam structure.

The FDA-approved product is Mozobil injection, containing plerixafor at 20 mg/mL. The commercial product is formulated for subcutaneous administration and is used with granulocyte-colony stimulating factor for stem-cell mobilization in specified lymphoma and multiple myeloma patients. [2]

The patent does not claim the modern clinical use of plerixafor in the manner of a narrowly drafted method-of-use patent. Its principal protection is composition and compound protection tied to the chemical structure and pharmaceutical composition.

When did RE42152 expire?

RE42,152 expired on December 10, 2013.

Event	Date
Earliest priority associated with the family	November 2, 1990
Original U.S. patent application	September 29, 1994
U.S. Patent No. 5,583,131 issued	December 10, 1996
Reissue patent RE42,152 issued	March 29, 2011
Original patent term expiration	December 10, 2013
Current status	Expired

The patent was governed by the pre-Uruguay Round patent-term rule applicable to the original filing. That rule generally provided 17 years from grant. The reissue patent retained the original patent’s expiration date. A reissue cannot be used to create a new 17-year term.

The earlier U.S. Patent No. 5,021,409, covering related bis-macrocyclic compounds, also expired before RE42,152. The two patents formed part of the early U.S. patent estate around the bicyclam discovery program. [3, 4]

What is the Orange Book status of RE42152?

RE42,152 was associated with the original patent estate for plerixafor and Mozobil. It is not a live Orange Book patent barrier today because it expired in 2013.

The Orange Book consequences are:

An expired patent cannot support a current Paragraph IV certification against a live listed patent.
A generic applicant may rely on patent expiration rather than challenge the patent’s validity or enforceability.
The patent does not block an ANDA based on a pharmaceutical equivalent to Mozobil.
Any current regulatory delay must arise from another listed patent, exclusivity period, or FDA requirement, not from RE42,152 itself.

Mozobil received FDA approval on December 15, 2008. It also received orphan-drug exclusivity for the approved indications. Orphan exclusivity is separate from patent protection and prevents FDA approval of the same drug for the same orphan indication during the applicable exclusivity period, subject to statutory exceptions. [2, 5]

Did RE42152 create method-of-use protection?

The supplied claims are primarily composition claims and compound claims. They do not establish a conventional method-of-use claim directed to:

stem-cell mobilization;
treatment of lymphoma;
treatment of multiple myeloma;
combination use with G-CSF; or
a specific dosing regimen.

Claim 1 includes the phrase “active against HIV,” which operates as a functional or intended-use limitation in a pharmaceutical composition claim. That limitation may affect claim construction depending on the accused composition and the applicable infringement analysis. It does not convert the patent into a modern clinical method-of-use patent for Mozobil’s approved stem-cell mobilization indications.

The commercial use of plerixafor was therefore supported primarily by the chemical and composition claims, regulatory exclusivity, manufacturing know-how, and later product development, rather than by a broad stem-cell-mobilization patent claim in RE42,152.

Are there claim-quality issues in the supplied text?

Yes. The supplied claim text contains apparent transcription, OCR, and dependency defects.

Examples include:

Claims 17-22 state “The compound of claim 1” but then recite a pharmaceutical composition.
Claim 18 contains inconsistent quotation and numbering around the two prime symbols.
Claim 19 contains duplicated and malformed structural language.
Claim 22 alternates between “1,5,9-triazacyclododecane” and “bis-1,5,9-triazacyclododecane.”
Claims 8 and 9 contain apparent numbering or nomenclature errors.
Claims 32-35 combine compound language with composition language.
Claim 1, as supplied, requires an “unsubstituted” aromatic or heteroaromatic A group, while later claims identify nitro, chloro, fluoro, methyl, bromo and phenyl-substituted linkers.

These defects matter for claim construction and validity analysis. A dependent claim cannot ordinarily broaden the claim from which it depends. If the official patent text contains the same inconsistencies, the disputed claims would require analysis of the issued patent, prosecution history, reissue record, written description, enablement, indefiniteness and possible correction doctrines. The cleaned-up commercial analysis should rely on the official USPTO text rather than the transcription provided.

How strong was the patent estate for plerixafor?

The estate was commercially strong during the pre-expiration period because the core molecule was distinctive and the main patent claims reached the active compound itself.

Strength factor	Assessment
Core molecule coverage	Strong while unexpired
Composition coverage	Broad, including multiple linker and macrocycle variants
Product-specific coverage	Direct coverage of plerixafor
Formulation coverage	Limited in RE42,152 compared with later product-specific patents
Method-of-use coverage	Limited; HIV-oriented claims do not mirror the approved Mozobil indication
Manufacturing protection	Not the principal focus of this patent
Current enforceability	None after expiration
Generic-entry risk today	Patent risk from RE42,152 is zero; other regulatory or patent issues must be assessed separately

The main weakness was term. Because the patent originated under the pre-1995 term regime, the commercial life of the patent ended approximately five years after Mozobil’s approval.

Which companies developed or challenged the plerixafor estate?

AnorMED developed the bicyclam program and plerixafor. Genzyme acquired AnorMED in 2006, bringing plerixafor into Genzyme’s commercial portfolio. Sanofi later acquired Genzyme and became the relevant sponsor associated with Mozobil. [6]

The competitive and development landscape includes:

Company or product	Relevance
AnorMED	Original developer of plerixafor
Genzyme	Acquired AnorMED and commercialized Mozobil
Sanofi	Successor commercial owner after acquiring Genzyme
Generic manufacturers	Potential ANDA applicants after patent expiration
BioLineRx, motixafortide	Competing CXCR4-directed stem-cell mobilization program
X4 Pharmaceuticals, mavorixafor	CXCR4 antagonist program with different chemistry and indications
Polyphor, balixafortide	Distinct CXCR4 antagonist program

These later CXCR4 antagonists are not automatically blocked by RE42,152 because the patent claims require the specified bis-macrocyclic polyamine architecture. A non-bicyclam CXCR4 antagonist generally falls outside the literal chemical genus.

What generic launch scenarios exist for plerixafor?

After December 10, 2013, the principal patent-based launch scenarios were:

Post-expiration ANDA launch. A generic applicant could wait for patent expiration and submit an ANDA without challenging RE42,152.
Paragraph IV filing before expiration. An applicant could certify that the patent was invalid, unenforceable or not infringed, subject to litigation and potential 30-month FDA stay provisions.
Regulatory-exclusivity timing. Even after patent expiration, orphan-drug exclusivity or other FDA exclusivity could affect approval for the protected indication.
Formulation or process differentiation. A generic applicant could use a formulation and manufacturing process that avoided separate, later-expiring patents, if any existed.
Authorized or branded-generic competition. The sponsor could compete through an authorized generic or contractual arrangement rather than relying solely on patent enforcement.

RE42,152 itself no longer changes the economics of these scenarios. Its primary present value is historical: it explains the original chemical exclusivity around plerixafor and identifies the core bicyclam structure that later competitors had to design around while the patent was live.

How does RE42152 compare with later plerixafor protection?

RE42,152 is a first-generation chemical patent. It is structurally broad but not tailored to the final approved product’s clinical use, dosage regimen or commercial formulation.

A later-stage plerixafor estate could include:

formulation patents;
dosing and administration patents;
combination-use patents;
manufacturing-process patents;
crystalline or salt-form patents;
injectable formulation patents; and
patents directed to stem-cell mobilization rather than HIV activity.

Those categories must be assessed independently. Expiration of RE42,152 does not establish that every patent ever associated with Mozobil has expired. It establishes only that the reissue patent itself no longer provides enforceable exclusivity.

Key Takeaways

RE42,152 covers bis-macrocyclic polyamine compounds and pharmaceutical compositions.
Plerixafor, the active ingredient in Mozobil, is directly represented by the para-phenylene-linked bicyclam claims.
The patent includes broad genus claims and narrower claims to phenylene, pyridine, thiophene, bipyridine, phenanthroline, substituted aromatic and metal-complex embodiments.
RE42,152 expired on December 10, 2013.
The reissue did not extend the original patent term.
The patent’s claims are primarily chemical composition and compound claims, not modern stem-cell-mobilization method claims.
The supplied claim text contains apparent OCR and dependency defects that require comparison with the official patent record.
RE42,152 is no longer a current Orange Book or Paragraph IV barrier.
Current plerixafor competition depends on FDA exclusivity, other patents, manufacturing capability and commercial access, not this expired reissue patent.

FAQs

What is the active ingredient covered by RE42152?

The principal commercial active ingredient is plerixafor, also called AMD3100. Its chemical structure is the para-phenylene-linked bis-1,4,8,11-tetraazacyclotetradecane compound.

Did RE42152 cover Mozobil’s stem-cell mobilization indication?

It covered the plerixafor compound and pharmaceutical compositions containing it. The patent’s express biological framing is anti-HIV activity, not a narrowly drafted stem-cell-mobilization method claim.

Can a generic company still infringe RE42152?

No. The patent expired on December 10, 2013. An expired patent cannot support a new infringement action based on post-expiration commercial activity.

Is plerixafor a biologic requiring a biosimilar application?

No. Plerixafor is a chemically synthesized small molecule. A competing product would generally follow the ANDA pathway for a suitable pharmaceutical equivalent, not the biosimilar pathway under the Public Health Service Act.

What is the main design-around strategy for the claimed bicyclam structure?

A developer could use a different macrocycle architecture, nonidentical macrocycles, a different linker system, or a non-bis-macrocyclic CXCR4 antagonist. These strategies mattered before expiration; they now remain relevant mainly to separate patent families and product differentiation.

References

U.S. Patent and Trademark Office. (2011). U.S. Patent No. RE42,152: Bis-macrocyclic compounds, and pharmaceutical compositions containing them.
U.S. Food and Drug Administration. (2008). Mozobil (plerixafor) prescribing information.
U.S. Patent and Trademark Office. (1991). U.S. Patent No. 5,021,409: Bis-macrocyclic compounds, and pharmaceutical compositions containing them.
U.S. Patent and Trademark Office. (1996). U.S. Patent No. 5,583,131: Bis-macrocyclic compounds, and pharmaceutical compositions containing them.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations, commonly known as the Orange Book.
Genzyme Corporation. (2006). Genzyme completes acquisition of AnorMED. Corporate transaction announcement.

PCT Information
PCT Filed	December 16, 1992	PCT Application Number:	PCT/GB92/02334
PCT Publication Date:	June 24, 1993	PCT Publication Number:	WO93/12096

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	0619813	⤷ Start Trial	CA 2009 00052	Denmark	⤷ Start Trial
European Patent Office	0619813	⤷ Start Trial	C300425	Netherlands	⤷ Start Trial
European Patent Office	0619813	⤷ Start Trial	SPC038/2009	Ireland	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: RE42152

Summary for Patent: RE42152