United States Drug Patent RE28636: Claim Scope, Expiration, Orange Book Status, and Patent Landscape

U.S. Patent RE28636 covers oral treatment using the fixed combination of sulfamethoxazole and trimethoprim, now commonly known as co-trimoxazole or TMP-SMX. Claim 7 is a broad method-of-treatment claim limited by the drug ratio, oral administration, bacterial disease, and sulfamethoxazole-resistant bacteria. Claim 8 narrows the claim to specified dose ranges.

The patent is an historical patent, not a current barrier to generic commercialization. Its term has expired, and the claimed combination is available from multiple generic manufacturers. The principal commercial risks today concern regulatory compliance, product quality, manufacturing controls, labeling, and other intellectual property rights rather than RE28636.

What drug combination does U.S. Patent RE28636 protect?

RE28636 protects a combination of:

Component	Chemical identity	Modern generic name
Sulfonamide	5-methyl-3-sulfanilamidoisoxazole	Sulfamethoxazole
Pyrimidine	2,4-diamino-5-(3,4,5-trimethoxybenzyl)pyrimidine	Trimethoprim

The combination is commonly identified as sulfamethoxazole/trimethoprim, TMP-SMX, or co-trimoxazole. Commercial products include oral tablets, double-strength tablets, and oral suspensions.

The claim language uses older terminology. “Sulfomethoxazole” in the supplied claim appears to refer to sulfamethoxazole. The chemical definition in the claim is the more important limitation because it identifies the active sulfonamide by structure.

The patent does not broadly claim either active ingredient alone. It requires a composition containing both the specified sulfonamide and the specified pyrimidine, or acceptable salts of those compounds.

What does claim 7 of RE28636 cover?

Claim 7 is a method-of-treatment claim. Its elements can be separated as follows:

Claim element	Scope
Claimed activity	Treating a warm-blooded animal
Disease requirement	The animal must have a bacterial disease
Resistance requirement	The disease must be caused by sulfamethoxazole-resistant bacterial strains
Route	Oral administration
Dose standard	A therapeutically effective amount
Composition	Sulfamethoxazole or an alkali-metal salt plus trimethoprim or an acid salt
Ratio	About 1 to about 30 parts sulfamethoxazole per one part trimethoprim

The claim therefore does not cover every use of TMP-SMX. It requires the combination to be used in the treatment of a bacterial disease caused by sulfamethoxazole-resistant bacteria.

How does the ratio limitation operate?

The composition must contain approximately 1 to 30 parts of sulfamethoxazole for each part of trimethoprim. The use of “about” introduces a possible tolerance around the numerical endpoints, but it does not eliminate the ratio limitation.

The standard 5:1 sulfamethoxazole-to-trimethoprim products fall within the claimed range:

Product strength	Sulfamethoxazole	Trimethoprim	Ratio
Single-strength tablet	400 mg	80 mg	5:1
Double-strength tablet	800 mg	160 mg	5:1
Common oral suspension dose equivalent	200 mg	40 mg	5:1

The claim is drafted with “comprising.” That term generally permits additional ingredients, including excipients, flavoring agents, stabilizers, preservatives, and other non-excluded components. It does not permit omission of either required active ingredient.

Does claim 7 cover nonoral TMP-SMX products?

No. Claim 7 expressly requires oral administration. An intravenous sulfamethoxazole/trimethoprim product would not satisfy the literal route limitation of this claim, although a different claim in the patent family could have had different scope. The supplied claims do not establish protection for injectable, topical, ophthalmic, or other nonoral products.

Does claim 7 cover treatment of ordinary susceptible infections?

The claim expressly requires disease caused by sulfamethoxazole-resistant strains. A use limited to bacteria susceptible to sulfamethoxazole would not meet that limitation on its face.

The resistance limitation creates a potentially material claim-construction and proof issue. In an infringement dispute, the patent owner would need to establish that the treated disease was caused by a strain meeting the claimed resistance condition. Patient records, microbiology results, susceptibility testing, prescribing instructions, and the label could become relevant.

What does claim 8 add to claim 7?

Claim 8 depends on claim 7 and narrows it to specified amounts:

250 mg to 750 mg of sulfamethoxazole or its alkali-metal salt; and
12.5 mg to 75 mg of trimethoprim or its acid salt.

The claim is directed to the amount of the active ingredients in the therapeutically effective composition. It does not expressly state whether those amounts must be administered per tablet, per dosage unit, per administration, or per daily regimen. That issue would depend on the patent specification, prosecution history, and the technical context in which the claim was construed.

What dosage ratios fall within claim 8?

The independent numerical ranges in claim 8 create a broader mathematical combination of possible ratios than the standard 5:1 commercial product:

Minimum possible ratio: 250 mg / 75 mg = approximately 3.33:1
Maximum possible ratio: 750 mg / 12.5 mg = 60:1

However, claim 8 depends on claim 7. The composition must still satisfy claim 7’s approximately 1:1 to 30:1 ratio limitation. As a result, the effective claim 8 ratio range is constrained by both sets of limitations.

Examples:

Sulfamethoxazole	Trimethoprim	Ratio	Within claim 8 ranges?	Within claim 7 ratio?
250 mg	12.5 mg	20:1	Yes	Yes
400 mg	80 mg	5:1	No, trimethoprim exceeds 75 mg	Yes
400 mg	80 mg	5:1	Commercially common	Yes, but not claim 8’s stated range
750 mg	75 mg	10:1	Yes	Yes
750 mg	12.5 mg	60:1	Yes numerically	No, exceeds claim 7 ratio
250 mg	75 mg	3.33:1	Yes numerically	Yes

The usual 400 mg/80 mg and 800 mg/160 mg strengths do not fall within claim 8’s stated trimethoprim range when measured as a single dosage unit. Claim 8 may have been directed to a particular dosing regimen, formulation, or administration context rather than the later standard tablet strengths. The complete specification is needed to resolve that issue definitively.

What patents protect sulfamethoxazole and trimethoprim today?

RE28636 does not provide current exclusivity. Its subject matter is part of the historical patent estate surrounding TMP-SMX, but the relevant patent term has expired.

The important distinction is between:

the original compound patents;
combination patents;
formulation patents;
method-of-use patents;
manufacturing or crystallization patents; and
regulatory exclusivity.

RE28636 is primarily a combination and method-of-treatment patent. It is not, based on the supplied claims, a patent directed to:

a novel sulfamethoxazole polymorph;
a novel trimethoprim polymorph;
a controlled-release delivery system;
a new suspension vehicle;
a manufacturing process;
a new indication unrelated to bacterial infection; or
a biologic or biosimilar product.

What formulations are protected by RE28636?

The supplied claims do not require a particular formulation technology. They cover a composition containing the two specified active ingredients and oral administration.

Potentially covered formulations could include:

immediate-release tablets;
capsules;
powders for oral suspension;
reconstituted oral suspensions; and
other oral compositions meeting the active-ingredient and ratio requirements.

The claims do not expressly require:

a particular tablet coating;
a particular excipient;
a particular particle size;
a particular dissolution profile;
a fixed-release mechanism; or
a specific manufacturing process.

A modern formulation patent would need to be analyzed separately. RE28636 cannot be used to infer protection for later formulation technology.

When did RE28636 lose exclusivity?

The patent is expired. Reissue practice does not restart or extend the underlying patent term beyond the enforceable term of the original patent, subject to the statutory rules applicable to the original patent and reissue. The patent’s historical term therefore does not create a present-day barrier to the sale of generic sulfamethoxazole/trimethoprim products. [1], [2]

The practical consequences are:

Issue	Current effect of RE28636
Generic launch	No current patent-based block
Paragraph IV filing	No live RE28636 patent challenge is required
Orange Book patent certification	No current listing should create a term-based barrier from RE28636
Licensing	No meaningful current exclusivity value from this patent
Litigation	Historical relevance only unless a separate dispute concerns past conduct
Formulation development	No current constraint from the supplied claims

What is the Orange Book status of RE28636?

RE28636 is not a current Orange Book barrier to generic TMP-SMX entry. The Orange Book lists patents and regulatory exclusivities associated with approved drug products, but an expired historical combination patent does not provide current exclusivity.

Bactrim and related sulfamethoxazole/trimethoprim products have long been subject to generic competition. The FDA-approved product category includes oral tablets and oral suspension products, as well as parenteral products. The specific patent listings for a particular reference product must be checked by application number and Orange Book edition because listings can vary by product and may include expired, delisted, or nonblocking records. [3]

RE28636 should not be treated as a current Orange Book patent term absent a current FDA listing expressly tied to an active approved application.

Are there Paragraph IV challenges to RE28636?

No current Paragraph IV strategy is commercially necessary against RE28636 because the patent has expired.

A Paragraph IV certification is directed to a listed patent that the applicant asserts is invalid, unenforceable, or not infringed. An expired patent generally does not block approval or launch. A generic applicant can proceed without waiting for the expired patent’s remaining term.

Historical ANDA filings may have addressed the listed patent while it was active. Those proceedings do not create current exclusivity. Paragraph IV litigation concerning the original Bactrim patent estate would therefore be relevant to historical launch timing, not to present-day market access.

Which companies compete in the TMP-SMX market?

The market is generic and has multiple suppliers. Depending on dosage form and market period, suppliers have included large generic manufacturers and specialty generic companies such as:

Amneal Pharmaceuticals;
ANI Pharmaceuticals;
Hikma Pharmaceuticals;
Mylan, now part of Viatris;
Sandoz;
Teva Pharmaceuticals;
Taro Pharmaceuticals; and
other FDA-approved manufacturers or contract suppliers.

The exact supplier set varies by product strength, dosage form, shortage status, and time period. Tablets, double-strength tablets, oral suspensions, and injectable products have different manufacturing and distribution profiles.

Because the active ingredients are old and the principal combination patents are expired, market share is generally driven by:

manufacturing cost;
supply reliability;
FDA compliance;
wholesaler contracts;
hospital purchasing;
suspension manufacturing capability;
product shortages; and
state and institutional formulary preferences.

What generic launch risks exist today?

RE28636 presents no meaningful current launch risk by itself. A generic applicant’s remaining risks are operational and regulatory.

FDA regulatory risks

Relevant FDA issues can include:

ANDA bioequivalence requirements;
dosage-form-specific performance;
stability of oral suspensions;
dissolution testing;
antimicrobial preservative performance;
manufacturing-site inspection findings;
data-integrity concerns;
labeling conformity; and
drug-shortage or supply-chain issues.

The active ingredients are small-molecule compounds, so biosimilar approval pathways do not apply. A sulfamethoxazole/trimethoprim generic is approved through the ANDA framework rather than the biosimilar pathway. [3], [4]

Manufacturing and intellectual-property barriers

Manufacturing barriers are more likely to arise from process know-how, supplier qualification, impurity control, and FDA quality systems than from RE28636.

Potential technical issues include:

control of sulfamethoxazole and trimethoprim assay;
degradation products;
suspension sedimentation and redispersibility;
content uniformity;
dissolution performance;
preservative effectiveness;
packaging compatibility; and
validated cleaning and cross-contamination controls.

These requirements can affect launch economics without creating patent exclusivity.

How strong is the patent estate for TMP-SMX?

The current patent estate is weak from an exclusivity perspective because the foundational compound and combination patents are long expired.

Patent-estate category	Current assessment
Active-ingredient patents	Expired
Historical combination patents	Expired
RE28636 claims 7 and 8	Expired
Formulation patents	Product-specific and must be separately verified
Method-of-use patents	No current blocking right established by the supplied claims
Manufacturing patents	Potentially relevant only if later patents exist and remain unexpired
Regulatory exclusivity	No biosimilar exclusivity issue; ordinary generic framework applies
Litigation risk from RE28636	Low to nonexistent for future sales

The commercial value of RE28636 is historical. It helped define the protected combination and treatment concept during the period when co-trimoxazole was being developed and commercialized. It does not support a present-day monopoly.

What patent litigation or settlements affect RE28636?

The supplied claims do not identify litigation, settlement agreements, licensees, or prosecution-history statements. No current litigation or settlement right can be attributed to RE28636 solely from the claim text.

A historical litigation review would need to distinguish among:

validity challenges to the original patent;
infringement claims involving Bactrim or equivalent products;
ANDA Paragraph IV cases;
settlements governing generic entry;
antitrust claims concerning branded and generic commercialization; and
later patent disputes involving dosage forms or manufacturing.

Those matters should not be treated as continuing restrictions after patent expiration. A settlement can affect a historical launch date, but it cannot revive an expired patent right.

How does RE28636 compare with modern drug patents?

RE28636 is narrower in some respects and broader in others than modern pharmaceutical claims.

It is narrower because it requires:

oral treatment;
a bacterial disease;
sulfamethoxazole-resistant strains; and
a specified drug ratio.

It is broader because it does not require:

a particular patient population;
a named infection;
a specific tablet design;
a specific excipient system;
a defined pharmacokinetic profile; or
a particular manufacturing method.

Modern patents often use more detailed formulation, dosing, patient-selection, biomarker, or polymorph limitations. RE28636 reflects an earlier combination-product strategy focused on synergistic antibacterial activity and treatment use.

Key Takeaways

RE28636 covers oral treatment using sulfamethoxazole and trimethoprim.
Claim 7 requires a sulfamethoxazole-to-trimethoprim ratio of about 1:1 to 30:1.
Claim 7 also requires bacterial disease caused by sulfamethoxazole-resistant strains.
Claim 8 narrows the composition to 250-750 mg sulfamethoxazole and 12.5-75 mg trimethoprim, subject to all limitations of claim 7.
The claims do not protect either active ingredient alone.
The claims do not expressly cover injectable or nonoral products.
RE28636 is expired and does not block current generic entry.
No biosimilar pathway applies because TMP-SMX is a small-molecule drug combination.
Current commercial barriers are more likely to involve FDA manufacturing compliance, supply reliability, formulation performance, and product-specific later patents.
Any present Orange Book or litigation assessment must be made at the product-application level rather than inferred from RE28636 alone.

FAQs About U.S. Patent RE28636 and TMP-SMX

Is Bactrim still protected by RE28636?

No. RE28636 is an expired historical patent and does not currently prevent generic sale of sulfamethoxazole/trimethoprim.

Does RE28636 cover the 800 mg/160 mg double-strength tablet?

The 5:1 active-ingredient ratio falls within claim 7. Claim 8 requires 12.5-75 mg of trimethoprim, so a 160 mg trimethoprim dosage unit would not fall within claim 8 if the claimed amounts are measured per dosage unit.

Does the patent cover trimethoprim alone?

No. The supplied claims require both trimethoprim and sulfamethoxazole.

Is sulfamethoxazole resistance required for infringement?

For claim 7, yes. The claim expressly requires treatment of a bacterial disease caused by sulfamethoxazole-resistant strains. Claim 8 inherits that limitation.

Can a company sell a new oral TMP-SMX suspension without licensing RE28636?

Yes, the expired patent does not require a current license. The product still must satisfy FDA approval, manufacturing, labeling, and quality requirements.

Does RE28636 protect a new use of TMP-SMX for a nonbacterial disease?

No. The supplied claims are directed to bacterial disease treatment and do not cover an unrelated nonbacterial indication.

References

United States Patent and Trademark Office. (n.d.). Manual of Patent Examining Procedure, Chapter 1400: Correction of patents. https://www.uspto.gov/web/offices/pac/mpep/mpep-1400.html
United States Code. (2024). 35 U.S.C. §§ 154, 251. https://uscode.house.gov/
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. https://www.fda.gov/drugs/drug-approvals-and-databases/orange-book-data-files
U.S. Food and Drug Administration. (2024). Generic drug facts. https://www.fda.gov/drugs/generic-drugs/generic-drug-facts

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Canada	1003331	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: RE28636

Summary for Patent: RE28636