| Abstract: | This invention concerns the use of compounds of formula
the N-oxides, the pharmaceutically acceptable addition salts, quaternary amines and the stereochemically isomeric forms thereof, wherein -a1=a2-a3=a4- forms a phenyl, pyridinyl, pyrimidinyl, pyridazinyl or pyrazinyl with the attached vinyl group; n is 0 to 4; and where possible 5; R1 is hydrogen, aryl, formyl, C1-6alkylcarbonyl, C1-6alkyl, C1-6alkyloxycarbonyl, substituted C1-6alkyl, or substituted C1-6alkyloxyC1-6alkylcarbonyl; each R2 independently is hydroxy, halo, optionally substituted C1-6alkyl, C2-6alkenyl or C2-6alkynyl, C3-7cycloalkyl, C1-6alkyloxy, C1-6alkyloxycarbonyl, carboxyl, cyano, nitro, amino, mono- or di(C1-6alkyl)amino, polyhalomethyl, polyhalomethyloxy, polyhalomethylthio, —S(═O)pR6, —NH—S(═O)pR6, —C(═O)R6, —NHC(═O)H, —C(═O)NHNH2, —NHC(═O)R6, —C(═NH)R6 or a 5-membered heterocyclic ring; p is 1 or 2; L is optionally substituted C1-10alkyl, C2-10alkenyl, C2-10alkynyl or C3-7cycloalkyl; or L is —X—R3 wherein R3 is optionally substituted phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl; X is —NR1—, —NH—NH—, —N═N—, —O—, —C(═O)—, —CHOH—, —S—, —S(═O)— or —S(═O)2—; Q is hydrogen, C1-6alkyl, halo, polyhalo-C1-6alkyl or an optionally substituted amino group; Y represents hydroxy, halo, C3-7cycloalkyl, optionally substituted C1-6alkyl, C2-6alkenyl or C2-6alkynyl, C1-6alkyloxy, C1-6alkyloxycarbonyl, carboxyl, cyano, nitro, amino, mono- or di(C1-6alkyl)amino, polyhalomethyl, polyhalomethyloxy, polyhalomethylthio, —S(═O)pR6, —NH—S(═O)pR6, —C(═O)R6, —NHC(═O)H, —C(═O)NHNH2, —NHC(═O)R6, —C(═NH)R6 or aryl; aryl is optionally substituted phenyl; Het is an optionally substituted heterocyclic radical; for the manufacture of a medicine for the treatment of subjects suffering from HIV (Human Immunodeficiency Virus) infection.
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Patent landscape, scope, and claims: |
US Patent 7,037,917: Scope of Claims, Claim Depth, and US Landscape for the HIV Pyrimidinyl Nucleoside-Targeting Combination Space
What does US 7,037,917 claim, in scope terms?
US 7,037,917 is built around a single substituted pyrimidinyl small molecule scaffold defined by a specific core structure, then layered into (i) solid forms and salt/amine variants, (ii) pharmaceutical compositions, (iii) combination regimens with broad HIV antiretroviral classes, and (iv) a process claim and clinical method claims.
The claim set you provided includes 32 claims (numbering as shown). The center of gravity is claim 1 (and dependent claim 2), with multiple downstream “system-level” claims covering formulations and combination therapy for HIV.
Core chemical definition (claims 1–2)
- Claim 1 defines a “pyrimidinyl compound” as:
- 4-[[4-amino-5-bromo-6-(4-cyano-2,6-dimethylphenyloxy)-2-pyrimidinyl]amino]benzonitrile, plus explicit allowable variations:
- N-oxide
- addition salt
- quaternary amine
- stereochemically isomeric form
- Claim 2 further restricts the pyrimidinyl compound to the same specific structure.
“What variants are within scope?” (claims 23–25)
The patent expressly pulls in:
- Addition salt (claim 23)
- Hydrochloride salt (claim 24)
- Quaternary amine form (claim 25)
This is important for freedom-to-operate (FTO) because it broadens coverage beyond the free base to specific derivative forms and key salt/amine states likely to be used in manufacturability, stability, and dosing.
Formulation coverage (claims 3, 26–30)
- Claim 3: pharmaceutical composition comprising a pharmaceutically acceptable carrier and an effective amount of the pyrimidinyl compound (claims 1 or 2).
- Claim 26: composition can be a tablet.
- Dose granularity:
- Claim 27: 1 to 1000 mg active per unit dosage form
- Claim 28: 5 to 200 mg per unit dosage form
- Claim 29: tablet where effective amount 1 to 1000 mg
- Claim 30: tablet where effective amount 5 to 200 mg
The dose windows in claims 28/30 create tighter sub-scope for tablet products.
Combination therapy coverage (claims 4–18)
This is the main “expansion” layer. The patent claims combinations of the pyrimidinyl compound with an antiretroviral compound, where that antiretroviral can be from a broad menu of drug classes and listed examples.
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Claim 4: combination comprising pyrimidinyl compound (claims 1 or 2) + an antiretroviral compound, where the antiretroviral comprises at least one of:
- nucleoside reverse transcriptase inhibitor (NRTI)
- non-nucleoside reverse transcriptase inhibitor (NNRTI)
- TIBO compound
- α-APA compound
- TAT-inhibitor
- protease inhibitor
- immunomodulating agent
- plus mixtures thereof
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Claims 5–6 provide enumerated exemplars:
- NRTIs (claim 5): zidovudine (AZT), didanosine (ddI), zalcitabine (ddC), lamivudine (3TC)
- NNRTIs (claim 6): suramine, pentamidine, thymopentin, castanospermine, efavirenz, dextran sulfate, foscarnet-sodium, nevirapine, tacrine (and mixtures)
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Specific named examples for TIBO/α-APA/protease/immunomodulating bucket (claims 7–10):
- TIBO (claim 7): (S)-8-chloro-4,5,6,7-tetrahydro-5-methyl-6-(3-methyl-2-butenyl)imidazo[4,5,1-jk][1,4]benzodiazepine-2(1H)-thione
- α-APA (claim 8): α-[(2-nitro-phenyl)amino]-2,6-dichlorobenzene-acetamide
- Protease inhibitors (claim 9): indinavir, ritonavir, saquinavir, ABT-378
- Other/third bucket (claim 10): RO-5-3335, levamisole, and mixtures
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Claims 11–16: each combination claim includes a pharmaceutically acceptable carrier in the combination context (carrier support for product-form claims).
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Claim 17: combination can be in a single preparation.
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Claim 18: such combination further comprises pharmaceutically acceptable carrier.
Process coverage (claims 19–20)
- Claim 19: process for preparing compound of claim 2 by reacting a compound of formula with NH3 in a reaction inert solvent.
- Claim 20: reacting is performed in the presence of a base.
This matters for manufacturing-route FTO, because it creates claim coverage tied to an NH3 amidination/ammonolysis-type step (as framed by “reacting ... with NH3”).
Clinical method coverage (claims 21–22, 31–32)
The patent extends beyond composition and combination into treatment methods.
- Claim 21: treating HIV infection via administering effective amount of pyrimidinyl compound (claims 1 or 2).
- Claim 22: treating HIV infection via administering effective amount of combination (claim 4).
- Claim 31: treating HIV-1 infection with acquired resistance to art-known NNRTIs via administering pyrimidinyl compound (claims 1 or 2).
- Claim 32: same resistance scenario but via administering the combination from claim 4, with additional administration sequencing flexibility:
- pyrimidinyl + antiretroviral administered simultaneously, separately or sequentially
This sequencing language is a key “productization” lever. It supports end-user infringement arguments against both fixed-dose and co-administered regimens.
How is claim scope structured? (Primary vs dependent layers)
The claims operate like a stack:
1) Chemical identity gate
- Claim 1 defines the exact pyrimidinyl compound plus derivative forms:
- N-oxide, addition salt, quaternary amine, stereoisomer.
- Claim 2 locks in the same structure as the pyrimidinyl compound.
2) Productization layer
- Claim 3: formulation with carrier.
- Claims 26–30: tablet dosage forms and mg ranges.
3) Regimen expansion layer
- Claim 4: combination with any antiretroviral that falls within enumerated HIV mechanism buckets.
- Claims 5–10: populate that antiretroviral bucket with specific named compounds.
- Claims 11–18 and 17: carriers and single-preparation embodiments.
4) Clinical method layer
- Claims 21–22: HIV treatment broadly.
- Claims 31–32: HIV-1 patients with acquired resistance to NNRTIs.
- Claim 32: administration schedule flexibility.
5) Manufacturing layer
- Claims 19–20: NH3 and base in inert solvent.
Where is the enforcement leverage strongest?
The strongest leverage for enforcement typically comes from the combination and method claims, because they reach downstream commercialization and clinical use, not only the chemical entity.
Combination breadth in claim 4 is unusually wide
Claim 4 does not require a single specific antiretroviral. It permits the antiretroviral to be drawn from multiple classes and mechanisms (NRTI, NNRTI, TIBO, α-APA, TAT inhibitor, protease inhibitors, immunomodulators). That creates multiple “entry points” for infringement even if the co-therapy differs by sponsor, region, or trial cohort.
Claim 32 reduces design-around paths via administration timing
Many combination-method claims are narrowed by requiring “together” or by a specific regimen. Claim 32 explicitly allows:
- simultaneously
- separately
- sequentially
That language supports infringement in clinical practice where patients take drugs at different times or via different dosage forms.
What does “scope” look like as a matrix?
Below is a practical mapping of what the claims cover.
| Claim area |
Covered subject matter |
Scope drivers |
| Chemical (1–2, 23–25) |
Exact pyrimidinyl structure + N-oxide, addition salt, hydrochloride salt, quaternary amine, stereoisomers |
Single scaffold controls coverage |
| Formulation (3, 26–30) |
Pharmaceutical composition (tablet) with specific mg ranges |
Tablet embodiment + mg windows |
| Combination (4–18) |
Pyrimidinyl compound + antiretroviral from multiple mechanistic buckets |
Broad class definition plus named exemplars |
| Method (21–22, 31–32) |
Treatment of HIV and HIV-1 NNRTI-resistant patients |
Administration route/time flexibility in claim 32 |
| Process (19–20) |
NH3 reaction in inert solvent, optionally with base |
Manufacturability step coverage |
What is the “competitive design-around” surface?
Even without external citations, the intrinsic claim language reveals where competitors could attempt to avoid scope:
Design-around levers (based on claim wording)
- Avoid using the exact pyrimidinyl compound scaffold or its explicit variants
- The scaffold is specific. Derivative forms within claim 1 (N-oxide, addition salt, quaternary amine, stereoisomers) are also captured.
- Change the dosing form outside the tablet embodiment
- Claim 26 specifies tablet. However, claim 3 is broader (pharmaceutically acceptable carrier) and is not limited to tablet. So switching dosage form may not fully avoid claim 3.
- Use antiretroviral agents outside the defined buckets
- Claim 4 includes multiple classes. If the co-agent is outside all buckets, combination coverage may narrow. But the list is broad across common HIV antiretroviral mechanisms and several other categories.
- Alter administration strategy
- Claim 32 permits simultaneous, separate, sequential. That is a wide window, leaving little to timing-based avoidance.
- Avoid the specific process step
- The process claim ties to reacting with NH3 in inert solvent, optionally with base. A competitor using a different synthetic route could avoid process claim infringement if it does not practice the claimed step.
US patent landscape implications (what this patent blocks)
Without prosecution history, assignee, priority dates, or citing/cited documents, only the structural landscape effect can be stated from the claims themselves:
Likely blocked activities
- Marketing a tablet formulation containing the pyrimidinyl compound within the mg ranges in claims 28/30.
- Co-marketing or clinical regimens where pyrimidinyl compound is used alongside:
- common NRTIs (AZT, ddI, ddC, 3TC),
- NNRTIs (e.g., efavirenz, nevirapine),
- protease inhibitors (indinavir, ritonavir, saquinavir, ABT-378),
- and specified TIBO/α-APA exemplars.
- Conducting or supporting clinical use in HIV-1 NNRTI-resistant populations under the claimed administration patterns (claim 31/32).
Likely manufacturing sensitivity
- Synthesis routes that include an NH3 reaction step under inert solvent (and base) could be implicated if the “compound of formula” corresponds to the claimed precursor-to-product transformation.
Key Takeaways
- The claims pivot on one exact pyrimidinyl compound and expressly pull in N-oxide, addition salt (including hydrochloride), quaternary amine, and stereoisomers.
- Product coverage is broad for compositions (claim 3) and becomes tablet-specific with dose windows (claims 26–30).
- Regimen coverage is the main expansion lever: claim 4 allows combination with multiple antiretroviral classes and several named examples, with product and carrier variants in claims 11–18.
- Method claims reinforce clinical infringement risk: claim 31 targets HIV-1 NNRTI-resistant patients; claim 32 allows simultaneous, separate, or sequential dosing, limiting timing-based design-arounds.
- Manufacturing is partially covered via an NH3/inert solvent (+ base) process step (claims 19–20).
FAQs
1) Does the patent cover only the free base of the pyrimidinyl compound?
No. Claim 1 includes N-oxides, addition salts, quaternary amines, and stereochemically isomeric forms, and dependent claims specify hydrochloride and quaternary amine.
2) Is the combination limited to a single antiretroviral drug?
No. Claim 4 defines the antiretroviral by mechanistic buckets and then claims specific exemplars in claims 5–10.
3) Can infringement occur if the co-therapy is given in separate pills or at different times?
Yes. Claim 32 allows the pyrimidinyl and antiretroviral to be administered simultaneously, separately or sequentially.
4) Does the patent claim only tablets?
It explicitly claims tablet embodiments (claims 26–30), but it also claims general pharmaceutical compositions in claim 3 without restricting to tablets.
5) Are there process claims that could affect manufacturing freedom-to-operate?
Yes. Claims 19–20 cover preparing the compound by reacting a precursor with NH3 in an inert solvent, optionally with a base.
References
- User-provided claim text for US Patent 7,037,917 (claims 1–32).
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