US Patent 5,614,560: Scope, Claims, and US Patent Landscape for Reducing Non-ischemic NMDA-Mediated Neuronal Degeneration
What is the core invention in US 5,614,560?
US 5,614,560 claims a method of reducing neuronal degeneration mediated by NMDA receptors in a mammal using compounds defined by a specific substituted adamantane / memantine-like structure (as shown by the application’s formula at claim level), with effective concentration administration.
The claims are structured around four buckets:
- Method of use (not a composition claim on its own).
- A broad structural formula covering a family of related amines and substituted variants.
- Inclusion of “physiologically acceptable salts” (salt forms fall within claim scope).
- Claimed clinical settings ranging from specific diseases to broad categories like long-term non-ischemic neurodegeneration and CNS trauma.
The net scope is a use claim for a defined chemical family where the defined family includes known NMDA antagonists (explicitly including amantadine, memantine, rimantadine in dependent claims).
What does claim 1 cover (independent claim scope)?
Claim 1 is the anchor. It recites:
- A method for reducing non-ischemic NMDA receptor-mediated neuronal degeneration in a mammal.
- Administering a compound of a specified formula (formula shown in the patent).
- Parameter constraints:
- R1 comprises an amino group
- R2 to R17 are independently H or a short chain aliphatic group with 1 to 5 carbons
- R4 and R10 may also independently be halogen or an acyl group, or a physiologically acceptable salt
- Administration at a concentration effective to reduce the degeneration.
Scope implications
- The method is defined by mechanism (NMDA receptor-mediated neuronal degeneration) and setting (non-ischemic).
- Chemical coverage is formula-based and allows variation across multiple substituent positions (R2-R17), plus permissive options at R4 and R10 (including halogen/acyl).
- “Physiologically acceptable salt” means that salts of covered bases are included without needing separate formulation claims.
Which dependent claims narrow to specific exemplars (amantadine, memantine, rimantadine)?
The dependent claims expressly identify representative members of the formula class:
Amantadine route
- Claim 2: R1 is NH2
- Claim 3: compound is amantadine
This locks that the “R1 is NH2” subset includes at least one named embodiment.
Memantine route
- Claim 6: R4 and R10 are methyl groups
- Claim 7: R1 is NH2
- Claim 8: compound is memantine
This ties memantine to the subset where both R4 and R10 = methyl and R1 = NH2.
Rimantadine route
- Claim 9: R1 is a substituted group (formula shown; X1 and X2 are independently H or 1–5 carbon aliphatic)
- Claim 10: X1 and X2 are (H/CH3) or (CH3/H)
- Claim 11: compound is rimantadine
- Claims 12-14: constrain R4 and R10 to methyl at one or both positions
These dependent claims function as literal support points within the broader formula in claim 1.
What disease and condition language expands real-world use coverage?
Claims 15 to 19 expand the eligible mammal “end states” beyond named drugs.
Specific neurological disease embodiments
- Claim 15: Huntington’s disease or amyotrophic lateral sclerosis
- Claim 16: condition selected from a list:
- neurolathyrism
- Guam disease
- olivo-pontocerebellar atrophy
- hyperglycinemia
- hepatic encephalopathy
- uremic encephalopathy
- 4-hydroxybuturic aciduria
- MELAS syndrome
- Rett syndrome
- homocysteinuria
- hyperprolinemia
- peripheral neuropathy
Broad clinical categories
- Claim 17: mammal subject to a long-term non-ischemic neurodegenerative disease
- Claim 18: mammal subject to central nervous system trauma
- Claim 19: mammal subject to poisoning from:
- carbon monoxide
- lead
- domoic acid
Scope implications
- The claim set is drafted to capture multiple real etiologies that can involve NMDA-mediated excitotoxicity or NMDA-linked pathology.
- The phrase “non-ischemic” limits the scope to non-ischemic mechanisms; ischemic stroke-like contexts are excluded by claim construction at the “setting” level.
How broad is the chemical element in the claims?
Chemical breadth is controlled by the general formula in claim 1:
- R1 must contain an amino group.
- R2-R17 each independently allow H or a 1-5 carbon aliphatic substituent.
- R4 and R10 have added options: halogen and acyl, in addition to the base allowed substituent types under the formula.
- The claim expressly incorporates physiologically acceptable salts.
Practical read-through
- The claim is not limited to a single exact compound. It is drafted to cover a family defined by allowable substituent patterns.
- The dependent claims demonstrate that at least three commercially known NMDA antagonists fall within scope:
- amantadine (via R1=NH2)
- memantine (via R4 and R10 methyl and R1=NH2)
- rimantadine (via the specified R1 substitution pattern and methyl at R4 and/or R10)
How would a competitor design around this claim set (high-level freedom-to-operate logic)?
A design-around must defeat at least one of the claim elements:
- Non-ischemic NMDA-mediated degeneration requirement (method setting/mechanism).
If a product targets ischemic pathways, the “non-ischemic” limitation becomes a likely boundary.
- Compound formula element (literal claim risk).
Changing the structure such that at least one core structural requirement is not met (for example, removing the required amino group at R1 or moving outside the allowed substitution pattern at R2-R17, R4, or R10) is the most direct risk reducer.
- Salt inclusion.
Salts of covered bases likely still infringe if the base is covered; avoiding covered bases avoids that route.
Because the independent claim is formula-defined, structural non-overlap is the strongest path to avoid literal infringement. If non-overlap is not possible, then avoiding the “reducing NMDA receptor-mediated neuronal degeneration” method element (for example, framing the use around non-NMDA mechanisms) creates a different infringement risk profile, but method claims still create exposure if the intended effect is NMDA-mediated.
What is the likely patent landscape shape around 5,614,560 in the US?
The claims as provided appear to cover method-of-treatment uses for amantadine/memantine/rimantadine-like NMDA antagonists in non-ischemic neurodegeneration and related toxicities.
In the US market, this kind of claim typically collides with three categories of prior art and competitor coverage:
1) Earlier NMDA antagonist use claims (broad excitotoxicity framing)
Before an issued method claim, earlier filings often claimed NMDA receptor antagonism in neurodegeneration and related conditions. If earlier art already taught NMDA antagonists for neuroprotection broadly, later patents may narrow to:
- “non-ischemic”
- a defined structural class
- specific disease lists or trauma/toxin settings
2) Composition claims for the drugs themselves
Even when the drug structure is known, composition protection and method protection can diverge. US 5,614,560’s focus on a method means it likely stands or falls on whether the claimed use and the defined compound family were non-obvious over the prior art and whether the drug uses were already disclosed.
3) Other memantine-related US filings (often spanning indication-specific claims)
Memantine has an indication history in neurodegeneration (notably Alzheimer’s disease), and US filings across the years often split into:
- specific disease claims
- dosing regimen claims
- salts and formulations
- mechanistic claims
US 5,614,560 specifically uses “non-ischemic NMDA receptor-mediated neuronal degeneration” and includes a wide disease/toxin list, which suggests it targets a distinct therapeutic use slice compared with standard dementia indications.
What does the claim construction hinge on (litigation-critical wording)?
From the provided claim text, the recurring construction points are:
- “reducing non-ischemic NMDA receptor-mediated neuronal degeneration”
Requires both: (i) non-ischemic setting, and (ii) NMDA receptor mediation tied to neuronal degeneration.
- “administering… a compound of the formula shown”
Chemical infringement turns on whether the accused compound matches the formula constraints (including R1 amino requirement and R2-R17/H-or-C1-C5 aliphatic allowances and the R4/R10 halogen/acyl possibilities).
- “concentration effective”
A typical method-of-treatment element. In practice, disputes often focus on whether the accused dosing achieves the claimed reduction effect.
- Disease/condition lists (claims 15-19)
Narrowing elements in dependent claims. If asserting claim 1 directly, the disease list is not required; if asserting dependent claims, the condition element becomes mandatory.
Claim-by-claim scope map (structured view)
| Claim |
Scope element |
Key limiting features |
| 1 |
Method for reducing non-ischemic NMDA receptor-mediated neuronal degeneration |
Administer compound of specified formula; R1 has amino; R2-R17 H or C1-C5 aliphatic; R4 & R10 may include halogen or acyl; includes physiologically acceptable salt |
| 2 |
R1 identity |
R1 = NH2 |
| 3 |
Example drug |
Compound = amantadine |
| 4 |
Substituent constraint |
R4 = methyl |
| 5 |
Substituent constraint |
R10 = methyl |
| 6 |
Joint constraint |
R4 and R10 = methyl |
| 7 |
R1 constraint |
R1 = NH2 |
| 8 |
Example drug |
Compound = memantine |
| 9 |
Alternative R1 structure |
R1 specified; X1 and X2 H or C1-C5 aliphatic |
| 10 |
X1/X2 selection |
X1/X2 are (H, CH3) or (CH3, H) |
| 11 |
Example drug |
Compound = rimantadine |
| 12 |
Substituent constraint |
R4 = methyl |
| 13 |
Substituent constraint |
R10 = methyl |
| 14 |
Joint constraint |
R4 and R10 = methyl |
| 15 |
Disease narrowing (dependent) |
Huntington’s disease or amyotrophic lateral sclerosis |
| 16 |
Condition list narrowing (dependent) |
neurolathyrism; Guam disease; olivo-pontocerebellar atrophy; hyperglycinemia; hepatic encephalopathy; uremic encephalopathy; 4-hydroxybuturic aciduria; MELAS; Rett; homocysteinuria; hyperprolinemia; peripheral neuropathy |
| 17 |
Category narrowing (dependent) |
long-term non-ischemic neurodegenerative disease |
| 18 |
Category narrowing (dependent) |
central nervous system trauma |
| 19 |
Toxicology narrowing (dependent) |
carbon monoxide, lead, or domoic acid poisoning |
Key Takeaways
- US 5,614,560 is a method-of-use patent targeting non-ischemic NMDA receptor-mediated neuronal degeneration.
- Claim 1 covers a formula-defined chemical family with mandatory R1 amino, flexible R2-R17 substitution, and specific options at R4/R10, plus physiologically acceptable salts.
- Dependent claims explicitly anchor the scope to amantadine (R1=NH2), memantine (R4=R10=methyl and R1=NH2), and rimantadine (specific R1 substitution pattern and methyl at R4 and/or R10).
- Dependent claims expand eligible clinical contexts with a disease list and broad categories (long-term non-ischemic neurodegeneration, CNS trauma, and specific poisonings).
- Competitive risk is driven primarily by whether an accused therapy uses a compound inside the claimed formula and is directed to NMDA-mediated, non-ischemic neurodegeneration.
FAQs
-
Does US 5,614,560 claim treatment with any NMDA antagonist?
No. It requires administration of a compound that fits the patent’s defined formula with specific substituent constraints and an amino-containing R1.
-
Are salts of the covered compounds included?
Yes. Claim 1 includes “physiologically acceptable salt thereof” for the listed substitutions.
-
Is ischemic neurodegeneration included?
No. The method is limited to non-ischemic NMDA receptor-mediated neuronal degeneration.
-
Which dependent claims name specific drugs?
Amantadine (claims 2-3), memantine (claims 6-8), and rimantadine (claims 9-11).
-
What conditions are covered beyond generic neuroprotection?
The dependent claims include Huntington’s disease, amyotrophic lateral sclerosis, multiple metabolic/toxic/degenerative conditions (claim 16), plus CNS trauma and poisoning from carbon monoxide, lead, or domoic acid.
References
[1] US Patent 5,614,560. Claims as provided in the user prompt.
