United States Patent 6,608,029: Amylin/Amylin-Agonist Analogue Claims for Reducing Gastric Motility and Delaying Gastric Emptying

Executive summary: US 6,608,029 is a method-of-treatment patent that claims administering an “amylin or amylin agonist” to reduce gastric motility or delay gastric emptying in mammals. The claim core narrows the covered therapeutic agent to a class of structured amylin-agonist analogues defined by (i) a specific amino-acid sequence with variable positions, (ii) an intramolecular linkage between two residues X and Y that can be a disulfide, lactam, or thioether, (iii) an N-terminus/side-chain and C-terminal Z selection set, (iv) optional D-amino-acid constraints in specific fallback combinations, and (v) a potency filter tied to “nucleus accumbens receptor binding activity” thresholds (≤5 nM, and dependent claims down to ≤1 nM and ≤50 pM). The dependent claims layer narrower embodiments: disulfide-linked X/Y, Z = amino, and parenteral administration. The estate, as framed by the provided claim set, is dominated by sequence-and-linkage claim scope rather than dosage, route, or disease-activity measures.

What does US 6,608,029 claim for amylin analogues that delay gastric emptying?

Answer (scope in one line): Administering a therapeutically effective amount of an amylin agonist analogue defined by a specific sequence architecture plus intramolecular linkage and receptor-binding potency thresholds to reduce gastric motility or delay gastric emptying in mammals.

Claim 1: independent method claim architecture

Claim 1 is a “method of reducing gastric motility or delaying gastric emptying” by administering a therapeutically effective amount of an amylin/amylin-agonist, where the operative limitation is that the agonist is an “amylin agonist analogue” with:

A fixed sequence framework with variable residue sets
- Sequence is expressed as:
  1A1-X-Asn-Thr-5Ala-Thr-Y-Ala-Thr-10Gln-Arg-Leu-B1-Asn-15Phe-Leu-C1-D1-E1-20F1-G1-Asn-H1-Gly-25Pro-I1-Leu-Pro-J1-30Thr-K1-Val-Gly-Ser-35Asn-Thr-Tyr-Z
- Variable positions:
  - A1 ∈ {Lys, Ala, Ser, hydrogen}
  - B1 ∈ {Ala, Ser, Thr}
  - C1 ∈ {Val, Leu, Ile}
  - D1 ∈ {His, Arg}
  - E1 ∈ {Ser, Thr}
  - F1 ∈ {Ser, Thr, Gln, Asn}
  - G1 ∈ {Asn, Gln, His}
  - H1 ∈ {Phe, Leu, Tyr}
  - I1 ∈ {Ile, Val, Ala, Leu} (and differs in later claims)
  - J1 ∈ {Ser, Pro, Thr} (later claims broaden/shift)
  - K1 ∈ {Asn, Asp, Gln}
  - X and Y are independently selected residues with side chains that are chemically bonded to each other, forming an intramolecular linkage; linkage comprises disulfide bond, lactam, or thioether
  - Z is a broad C-terminal substituent class: amino / alkylamino / dialkylamino / cycloalkylamino / arylamino / aralkylamino / alkyloxy / aryloxy / aralkyloxy.
A “provided that” constraint that creates fallback sub-genera Claim 1 contains conditional language that, when the enumerated combination of residues occurs, then:
- one or more of A1–K1 is a D-amino acid; and
- Z must be selected from amino/alkylamino/dialkylamino/cycloalkylamino/aryl/arylalkylamino/alkoxy/aryloxy/aralkyloxy (i.e., the same Z class, but now tied to the D-amino trigger).
A potency filter tied to nucleus accumbens receptor binding
- “said agonist exhibits a nucleus accumbens receptor binding activity of 5 nM or less.”

Claim 2–3: linkage and Z narrowing

Claim 2: X and Y comprise Cys residues linked by a disulfide bond.
Claim 3: Z is amino (a narrower end-group than the full Z genus).

Claim 4: route

Claim 4: agonist is administered parenterally.

Claims 5–7: receptor-binding potency escalation

Claim 5: binding activity ≤1 nM
Claim 6: binding activity ≤50 pM
Claim 7: a second independent method claim with an alternative sequence variant (see next section), but it repeats the “≤5 nM or less” filter.

Claims 7–19: multiple independent claim variants with sequence permutations

The provided text includes repeated “method comprising administering…” independent claim blocks (7, 13, 19), each with:

the same general sequence scaffold
but specific residue assignments differ for at least I1, J1, K1, and the conditional D-amino/Z trigger uses different residue combinations.

Practical effect: the patent claims a set of closely related agonist analogues defined by a narrow motif but with discrete options at variable positions and further discrete independent claim coverage for particular combinations.

How broad is US 6,608,029’s sequence claim scope and variable coverage?

Answer: Broad at the level of variable residue sets (A1–K1 and X/Y and Z), but constrained by (i) the exact sequence backbone positions, (ii) intramolecular linkage chemistry classes, and (iii) nucleus accumbens receptor-binding activity thresholds.

Variable position combinatorics

The claim uses a mixture of:
- hard fixed residues (Asn, Thr, Ala, Gln, Arg, Leu, Phe, Gly, Pro, Val, Ser, Tyr and other backbone anchors appear fixed in many positions); and
- soft variable positions (A1, B1, C1, D1, E1, F1, G1, H1, I1, J1, K1; plus X/Y and Z).

This structure matters for design-around:

Substituting residues outside each enumerated set likely removes literal coverage.
Modifying the backbone pattern (e.g., swapping fixed residues) likely breaks the claim.

Intramolecular linkage is a major claim lever

Claim 1 allows X/Y linkage to be:

disulfide, lactam, or thioether. That means the patent reaches beyond simple cystine-style constraints and includes engineered cyclizations or side-chain-to-side-chain covalent tether equivalents.

Claim 2 then narrows to the disulfide embodiment (Cys residues linked by a disulfide bond).

Z defines C-terminal end-group scope

Z is written as a wide genus of amino and O-alkyl/O-aryl groups. Claims 3 and 15 narrow Z to “amino.”

Design-around implication:

Moving from an amino end-group to, for example, an O-alkyl or aryl oxy group stays within the Z genus; removing the substituent class or changing to a non-enumerated functionality likely avoids literal coverage.

Which fallback residue combinations trigger D-amino-acid requirements under US 6,608,029?

Answer: The D-amino requirement activates only when specific residue combination(s) at A1–K1 positions occur, creating contingent sub-genera inside the broader variable sets.

Conditional triggers as stated in the claim text

Two explicit conditional patterns appear in the first independent claim block:

Trigger (a) (as stated for claim 1):
- A1 = Lys
- B1 = Ala
- C1 = Val
- D1 = Arg
- E1 = Ser
- F1 = Ser
- G1 = Asn
- H1 = Leu
- I1 = Val
- J1 = Pro
- K1 = Asn
  Then: one or more of A1–K1 is D-amino acid, and Z must be from the enumerated Z group.
Trigger (b):
- A1 = Lys
- B1 = Ala
- C1 = Val
- D1 = His
- E1 = Ser
- F1 = Asn
- G1 = Asn
- H1 = Leu
- I1 = Val
- J1 = Ser
- K1 = Asn
  Then: same D-amino and Z condition.

Independent claim blocks later alter the triggers

The text shows additional independent claim blocks (13, 19) with different trigger residue combinations, including changes in I1/J1/K1 arrangements. This means the patent’s “D-amino” constraint is not a universal requirement but a structural condition attached to specific sequence variants.

What do the nucleus accumbens receptor-binding activity thresholds mean for patent infringement risk?

Answer: The claims are limited by binding potency to a “nucleus accumbens receptor,” with explicit cutoffs that can sharply affect literal infringement.

Threshold ladder inside the claim set

Core independent coverage: ≤5 nM
Dependent ladder:
- ≤1 nM (claims 5, 11, 17, 21)
- ≤50 pM (claims 6, 12, 18, 22)

How the potency filter narrows enforcement

Even if a competitor’s analogue matches the sequence and linkage constraints, failure to meet the binding cutoff can avoid literal infringement for those threshold-dependent claims and, depending on claim construction, may also undermine coverage of the independent threshold-limited claim.

For claim 1 and its independent variants, the potency limit is intrinsic to the “agonist” definition. In practice, that makes potency testing and assay selection central to infringement analysis.

What are the key dependent claim limitations (route, Z, disulfide linkage, potency)?

Answer: The dependent claims create four principal narrowing axes: linkage chemistry, C-terminal end-group identity, administration route, and tighter potency bands.

Narrowing axes

Disulfide tether: Claim 2 (and corresponding claim 8, 14 depending on the independent block)
C-terminal amino: Claim 3 (and corresponding claim 9, 15)
Parenteral administration: Claim 4 (and corresponding claim 10, 16, 20)
Potency:
- ≤1 nM (claims 5, 11, 17, 21)
- ≤50 pM (claims 6, 12, 18, 22)

How many independent “method” claim variants does US 6,608,029 cover?

Answer: At least three independent method claim blocks appear in the provided text: claim 1, claim 7, and claim 13, plus a third sequence variant under claim 19. Each uses the same treatment theme but with different residue-assignments and conditional D-amino triggers.

Sequence variant differences visible in the claim text

Claim 1: I1 includes Ile/Val/Ala/Leu; J1 includes Ser/Pro/Thr.
Claim 7: I1 appears restricted to Ile/Val/Ala/Leu with J1 expanded to Ser/Pro/Leu/Ile/Thr in that block; also shows different provided-condition patterns.
Claim 13: shows a different assignment where I1 can be Ala or Pro in that block and has a distinct provided-condition trigger.
Claim 19: shows another modification: J1 is restricted to Asn/Asp/Gln in that block, plus different trigger residues and the nucleus accumbens cutoff tied to ≤5 nM.

What patent landscape can be inferred from this claim set for amylin agonists targeting gastric emptying?

Answer: The claim style indicates a patent focused on late-stage competitive positioning in the class of amylin analogues used to modulate GI motility. The key estate feature is that coverage is anchored to specific analogue architectures and receptor-binding potency rather than broad “amylin” compositions or general method-of-use.

Landscape implications for generic/competitor design

Given the claims:

Coverage likely concentrates on therapeutically effective administration of specific agonist analogues.
If competitor molecules keep the same backbone but change:
- the intramolecular linkage type (e.g., move away from disulfide/lactam/thioether) or
- the C-terminal Z group outside the enumerated classes, or
- the binding activity above thresholds, then literal infringement risk drops.

If competitor molecules:

maintain the backbone and linkage chemistry and achieve nucleus accumbens binding potency within ≤5 nM, then literal infringement risk rises, especially if the sequence matches the enumerated variable sets and the dependent narrowing embodiments are met.

What are the likely enforcement targets: product, molecule, or method?

Answer: The patent is enforced against the act of administering the defined agonist analogue to reduce gastric motility or delay gastric emptying. The molecule definition is necessary, but the claim is method-based.

Litigation focus points for US cases

Whether the accused product’s active analogue matches the claimed sequence and allowed substitutions.
Whether X/Y linkage chemistry corresponds to disulfide, lactam, or thioether variants.
Whether the receptor-binding assay and results satisfy the nucleus accumbens potency cutoffs.
Whether administration is “parenteral” for dependent claims that add that limitation.

Key claim-scope matrix (what must be true for literal infringement)

Claim element	Literal requirement (per provided text)	Practical infringement lever
Indication / method	Reduce gastric motility or delay gastric emptying in mammal	Behavioral/clinical endpoint characterization
Agent	Amylin or amylin agonist; must be an amylin agonist analogue with stated sequence architecture	Active analogue identification
Sequence	Backbone fixed with variable sets at A1–K1; X/Y placeholders and Z end-group	Amino-acid sequence matching
Linkage	X/Y side chains chemically bonded; intramolecular linkage is disulfide, lactam, or thioether	Chemical cyclization/tether design
D-amino trigger	Only when specific A1–K1 combinations occur (fallback conditions)	Only affects certain analogue variants
C-terminal Z	amino / alkylamino / dialkylamino / cycloalkylamino / arylamino / aralkylamino / alkyloxy / aryloxy / aralkyloxy	Terminal chemistry
Potency	nucleus accumbens receptor binding activity ≤5 nM (independent), with dependent tighter cutoffs	Assay method and result

How does US 6,608,029 compare with broader “amylin” method claims?

Answer: Compared with generic “amylin” method-of-use claims, this patent is narrower because it defines the therapeutic agent with a specific sequence and structural tether plus receptor-binding potency thresholds.

Consequences

It is less likely to read on a wide range of unrelated amylin agonists.
It is more likely to be a strong barrier against close analogues designed to preserve the core peptide scaffold but alter only minor substituents, provided potency and linkage remain within the claimed ranges.

What is the commercial and R&D relevance of the sequence-plus-potency claim strategy?

Answer: It is a claim strategy that can support differentiated enforcement against a molecular class rather than just a dosing regimen. For R&D, it makes analogue engineering around X/Y linkage, C-terminal Z, and potency thresholds the main levers.

R&D design-around themes suggested by the claim text

Change the linkage chemistry outside disulfide/lactam/thioether embodiments.
Use a C-terminal Z outside the enumerated groups.
Preserve the backbone pattern but push nucleus accumbens binding above the claimed thresholds (if feasible while retaining GI activity).
Avoid sequence identity at variable positions outside the enumerated sets, especially at anchor positions like C1/D1/E1/F1/G1/H1.

(These are claim-driven levers derived from the text; they indicate where freedom-to-operate analyses typically concentrate.)

Key Takeaways

US 6,608,029 is a method-of-use patent that turns on administration of a defined amylin agonist analogue to reduce gastric motility or delay gastric emptying.
Coverage is agent-anchored: the analogue must meet a specific sequence framework with variable residues A1–K1, an intramolecular tether (disulfide, lactam, or thioether) formed by X/Y, and an enumerated C-terminal group Z.
Potency is part of the claim definition via nucleus accumbens receptor binding thresholds: independent coverage is ≤5 nM, with dependent claims down to ≤1 nM and ≤50 pM.
Dependent claims narrow by tether chemistry (disulfide), C-terminal end-group (Z = amino), and route (parenteral).
Literal infringement risk is highest for close analogues that match sequence options, linkage chemistry, terminal Z group, and receptor binding thresholds.

FAQs

Does US 6,608,029 cover oral administration of an amylin analogue for delayed gastric emptying?
The provided claim set only explicitly limits a dependent embodiment to parenteral administration; oral coverage would not be literal under the parenteral-dependent claims.
Can an amylin agonist analogue with lactam tether X/Y fall within US 6,608,029?
Yes, claim 1 includes lactam as an acceptable intramolecular linkage type for X/Y.
Is Z = amino required for all covered analogues?
No. Z = amino appears as a dependent narrowing limitation (e.g., claim 3 and corresponding dependent claims), while claim 1 allows a wide Z genus.
What is the maximum nucleus accumbens receptor binding threshold for the independent method claims?
≤5 nM.
Is the D-amino-acid requirement always present in the claimed analogues?
No. The D-amino constraint is activated only under specified residue combination conditions stated in the “provided that” clauses.

References

United States Patent 6,608,029, “Method for reducing gastric motility or delaying gastric emptying using amylin or amylin agonist analogues,” claim text as provided in the prompt.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	197549	⤷ Start Trial
Australia	7685894	⤷ Start Trial
Bulgaria	100463	⤷ Start Trial
Brazil	9407424	⤷ Start Trial
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Details for Patent: 6,608,029

Summary for Patent: 6,608,029