US Patent 8,247,416 (Scope, Claims, and Landscape)
What does US 8,247,416 claim?
US Patent 8,247,416 is a US-issued patent centered on a single active small molecule and its defined solid-state form. The claims fall into two buckets: (i) crystalline form identification by powder X-ray diffraction (PXRD) peak lists and (ii) a preparation method using a specific coupling step.
Claim 1: “Compound + crystalline form” by PXRD peak set
Claim 1 is limited to:
- Compound identity (active):
4-[3-(4-cyclopropanecarbonyl-piperazine-1-carbonyl)-4-fluoro-benzyl]-2H-phthalazin-1-one
- Crystalline form defined by PXRD: powder X-ray diffraction peaks at Cu Kα (λ = 1.5418 Å), with tolerance ±0.1° in 2θ.
Claim 1 PXRD peaks (5 total):
| Peak # |
2θ (±0.1°), degrees |
λ (Å) |
| 1 |
12.0 |
1.5418 |
| 2 |
17.8 |
1.5418 |
| 3 |
21.1 |
1.5418 |
| 4 |
22.3 |
1.5418 |
| 5 |
29.2 |
1.5418 |
Legal scope effect: Claim 1 does not cover the compound in any physical form. It covers the specific crystalline form (or an at least substantially matching PXRD pattern) evidenced by those peak positions under the stated measurement conditions.
Claim 2: “Compound + crystalline form” with additional PXRD peaks
Claim 2 depends on claim 1 and adds a second peak list. It still requires the compound and the claim 1 peaks, plus these extra peaks:
Claim 2 additional PXRD peaks (peaks #6-10, 5 additional total):
| Peak # |
2θ (±0.1°), degrees |
λ (Å) |
| 6 |
10.5 |
1.5418 |
| 7 |
14.0 |
1.5418 |
| 8 |
21.7 |
1.5418 |
| 9 |
24.3 |
1.5418 |
| 10 |
26.1 |
1.5418 |
Legal scope effect: Claim 2 is narrower than claim 1 because it requires a broader match to a fuller PXRD fingerprint.
Claim 3: Melting/DSC onset temperature
Claim 3 depends on claim 1 and adds a thermal criterion:
- Melting behavior: begins melting at 210.1° C ± 1° C
- DSC test conditions: heated from 25° C to 325° C at 10° C/min
Legal scope effect: This is another solid-state discriminator. It narrows coverage to the crystalline form(s) exhibiting that DSC melting onset under the stated ramp.
Claim 4: Synthesis method to make the same compound
Claim 4 is a method claim with a specific transformation:
- Starting material:
2-fluoro-5-(4-oxo-3,4-dihydro-phthalazin-1-ylmethyl)-benzoic acid
- Reagent coupling partner:
1-(cyclopropylcarbonyl)piperazine or a mineral acid salt of that reagent
- Conditions: presence of an amide coupling agent and a base
- Transformation: forms the claimed compound:
4-[3-(4-cyclopropanecarbonyl-piperazine-1-carbonyl)-4-fluoro-benzyl]-2H-phthalazin-1-one
Legal scope effect: It is not just “any synthesis.” It requires the specific substrate and the coupling of the cyclopropylcarbonyl-piperazine moiety under amide-coupling conditions. It can constrain potential “design-around” routes if third parties use different intermediates or different coupling chemistry.
How do the claim elements work together (scope map)?
The patent’s enforcement leverage comes from combining:
- Specific chemical structure (the phthalazinone with fluorobenzyl and cyclopropanecarbonyl-piperazine-1-carboxamide linkage).
- Solid-state fingerprinting by PXRD with stated wavelength and tolerance.
- A thermal criterion (DSC onset melting).
- A specific method route from a named carboxylic acid intermediate using amide coupling.
A practical scope map:
| Claim |
What must be true for infringement |
| 1 |
Product must be the named compound and be present as a crystalline form whose PXRD shows the five specified peaks (2θ values within ±0.1°, λ=1.5418 Å). |
| 2 |
Everything in claim 1 plus additional PXRD peaks at 10.5, 14.0, 21.7, 24.3, 26.1 (±0.1°, λ=1.5418 Å). |
| 3 |
Everything in claim 1 plus DSC begins melting at 210.1°C ± 1°C under 10°C/min from 25°C to 325°C. |
| 4 |
A synthesis that starts from the named phthalazinone-ylmethyl benzoic acid, uses 1-(cyclopropylcarbonyl)piperazine (or its mineral acid salt), and proceeds via an amide coupling agent and base to yield the compound. |
What is the competitive “surface area” for infringement?
Because claims 1-3 are solid-form claims, the highest-risk scenario for generic or alternative-manufacturer actors is producing a material whose physical form matches the claimed PXRD/DSC criteria. The risk is lower if the product is:
- the same molecule but different polymorph/solvate with shifted or missing PXRD peaks, or
- a mixture where the characteristic peaks do not meet the claimed set within the specified tolerance.
For claim 4, risk clusters around:
- use of the named fluoro-phthalazinone benzoic acid intermediate, and
- execution of an amide coupling step with 1-(cyclopropylcarbonyl)piperazine (or mineral salt) under base.
A route that uses a different intermediate (e.g., activated acid via different functionalization, different protecting-group strategy, or different linker-forming approach) can reduce proximity to claim 4 even if it makes the same final compound.
What is the patent landscape around US 8,247,416?
How to interpret the landscape given the claim type
US 8,247,416 is structured as a form/thermal fingerprint plus a synthesis claim. In typical small-molecule pharma landscapes, that structure correlates with follow-on filings in one or more adjacent areas:
- Other solid forms of the same API (different PXRD peak sets, hydrates, solvates, amorphous).
- Different processing conditions to obtain the claimed form (crystallization/recrystallization parameters).
- Alternate intermediates or synthetic routes that avoid the exact method steps of the dependent method claim.
- Form-dependent patents that extend exclusivity in jurisdictions that recognize polymorph-form patents.
However, a precise mapping of “who owns what” requires bibliographic and family data that is not present in the provided input.
What can be concluded from the claim scope alone?
Even without bibliographic family data, the claim construction itself implies landscape pressure points:
1) PXRD peak-set claims create a “form arms race”
- Competitors often file around by developing a different polymorph that lacks one or more of the required peaks (10.5, 12.0, 14.0, 17.8, 21.1, 21.7, 22.3, 24.3, 26.1, 29.2 in the claimed fingerprint).
- If a competitor can show the marketed crystalline form does not match the specific 2θ list within ±0.1° (λ=1.5418 Å), they reduce exposure to claims 1-3.
2) DSC onset temperature acts as a second gate
Even if PXRD is close, claim 3 provides a second physical criterion:
- melting onset at 210.1°C ± 1°C under defined DSC conditions.
If the marketed solid melts outside that range under the specified heating ramp, claim 3 becomes harder to enforce.
3) Method claim narrows the “route-to-market” risk
Claim 4 is not “any synthesis.” It is anchored to:
- the named acid intermediate and
- the specified piperazine carbonylation reagent plus amide coupling conditions.
This structure often leads to two mitigation approaches:
- changing the synthetic logic so the named acid intermediate is not used in the same way, or
- using the same intermediate but performing the coupling with different reagent identities or coupling agent logic that falls outside the literal claim.
Operational implications for R&D and generic strategy
If you are developing an alternative crystalline form
Your target is to avoid meeting the asserted physical fingerprints:
- Avoid having the material’s PXRD peaks align with the full claim 2 set (10.5, 12.0, 14.0, 17.8, 21.1, 21.7, 22.3, 24.3, 26.1, 29.2 at λ=1.5418 Å within ±0.1° in 2θ).
- Avoid matching the DSC onset at 210.1°C ± 1°C (10°C/min, 25°C to 325°C).
If you are developing a “same molecule” but different solid
Solid-form freedom is constrained by the fact that claim 1 still requires exactly stated peak positions under defined instrumental conditions. Practical mitigation is to generate and qualify a form whose PXRD does not reproduce the list.
If you are planning process transfer
For method risk, the decision boundary is whether your route includes:
- the exact acid starting material (as named in claim 4),
- the use of 1-(cyclopropylcarbonyl)piperazine (or its mineral acid salt),
- and an amide coupling agent + base step leading to the API.
Key Takeaways
- US 8,247,416 centers on one active API plus a defined crystalline form, using Cu Kα PXRD peak lists (λ=1.5418 Å) with ±0.1° 2θ tolerance.
- Claim 1 requires the API and five PXRD peaks (12.0, 17.8, 21.1, 22.3, 29.2).
- Claim 2 tightens the solid-state requirement by adding five more PXRD peaks (10.5, 14.0, 21.7, 24.3, 26.1).
- Claim 3 adds a thermal gate: DSC melting onset at 210.1°C ± 1°C under 10°C/min from 25°C to 325°C.
- Claim 4 is a route-to-API method claim anchored to a named acid intermediate plus 1-(cyclopropylcarbonyl)piperazine (or mineral salt) with amide coupling agent + base.
FAQs
-
Does US 8,247,416 cover the compound in any crystal form?
No. Claims 1-3 require the specific crystalline form defined by PXRD peak positions (and DSC melting behavior for claim 3).
-
What is the tolerance in the PXRD peaks?
±0.1° in 2θ, using λ = 1.5418 Å.
-
Which claim is most restrictive on physical form?
Claim 2 is more restrictive than claim 1 because it requires an expanded PXRD fingerprint. Claim 3 adds a DSC constraint on top of claim 1.
-
Is the method claim broad enough to cover any synthesis route?
No. Claim 4 requires use of the named 2-fluoro-5-(4-oxo-3,4-dihydro-phthalazin-1-ylmethyl)-benzoic acid intermediate, the specified piperazine reagent, and amide coupling conditions.
-
If a competitor makes the same molecule, do they automatically infringe?
Not automatically. They must also make the product with a solid form meeting the specific PXRD/DSC requirements (claims 1-3), or follow the specific route (claim 4).
References (APA)
[1] United States Patent 8,247,416. (n.d.). Crystalline forms and synthetic methods for 4-[3-(4-cyclopropanecarbonyl-piperazine-1-carbonyl)-4-fluoro-benzyl]-2H-phthalazin-1-one.
