Patent: 10,189,833

Summary for Patent: 10,189,833

Title:	Solid forms of a compound modulating kinases
Abstract:	Solid forms of the compound, [5-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-(6-triflu- oromethyl-pyridin-3-ylmethyl)-amine HCl salt (Compound I) and its free base, active on the receptor protein kinases c-Kit and/or c-Fms and/or Flt3, were prepared and characterized: ##STR00001## Also provided are methods of using the solid forms.
Inventor(s):	Ibrahim; Prabha N. (Mountain View, CA), Visor; Gary Conard (Castro Valley, CA)
Assignee:	Plexxikon Inc. (Berkeley, CA)
Application Number:	15/725,197
Patent Claims:	see list of patent claims

US Patent 10,189,833 crystalline Compound I: what claims are actually covered and where exclusivity can break

US Patent 10,189,833 claims methods of treatment using a specific crystalline form of “Compound I,” defined by an X-ray powder diffraction (XRPD) fingerprint with peaks at 7.3, 23.3 and 28.2 (±0.2) 2θ (Cu-Kα). The patent estate is structurally built around (1) a polymorph definition, (2) broad kinase and immune-cell mediation targets (c-FMS, c-Kit, Flt3 and macrophages/microglia), and (3) a long list of disease areas, with add-on dependent claims for combination therapies (sirolimus, paclitaxel, durvalumab) and specific cancer indications.

The practical risk for generic/biosimilar entry is mainly not “Compound I itself,” but whether any generic can lawfully launch a different polymorph (different XRPD peaks), a non-crystalline form (amorphous/solvates/hydrates), or an alternative solid form not meeting the defined XRPD signature, while still meeting FDA’s bioequivalence and safety requirements. The litigation and licensing leverage sits with the polymorph scope and with claim drafting that uses method-of-use expansion.

---

What is US Patent 10,189,833 and what do its key claims cover?

What is the core claim construction in claims 1 and 2?

Claims 1 and 2 are the anchor:

• Claim 1 (method): treating a disease/condition mediated by a protein kinase selected from c-FMS, c-Kit, Flt3 (or combination) or mediated by macrophages or microglia, by administering a therapeutically effective amount of a crystalline form of Compound I defined by XRPD peaks at 7.3, 23.3, 28.2 (±0.2) using Cu-Kα.

• Claim 2 (composition): same as claim 1, but framed as administering a composition containing the crystalline form plus a pharmaceutically acceptable excipient.

This is a typical polymorph-defined medical use patent: infringement depends on whether the administered drug product contains (or is made up of) the claimed crystalline form as proven by the specified XRPD pattern under the specified measurement conditions.

What does the XRPD definition do legally?

The XRPD limitation makes the claim a material-identity claim. A competitor can attempt to avoid infringement by:

• Launching a different polymorph of Compound I that does not show the specified peak set (or shows them outside ±0.2).
• Launching a solvate/hydrate with different XRPD.
• Launching amorphous material, provided it does not reproduce the same fingerprint in the XRPD method window.
• Using measurement variance arguments (instrument settings, sample prep, peak fitting) only to the extent they can maintain a different “crystalline form” under expert analysis.

From a litigation posture, this shifts the dispute toward expert crystallography and product characterization rather than solely pharmacology.

What do claims 3 and 22 do to indication breadth?

• Claim 3 expands “disease or condition” to a long, explicit list including CNS diseases (Alzheimer’s, epilepsy, tauopathies), neuroinflammation disorders, multiple cancers (NSCLC, ovarian, colon, endometrial, esophageal, glioma, glioblastoma, hepatocellular carcinoma, melanoma, mesothelioma, pancreatic), hematologic malignancies (AML, CLL, Hodgkin lymphoma, monocytic leukemia), sarcomas/tumors (MPNST, plexiform neurofibromas, GCT, TGCT), ophthalmic disease (anterior/posterior eye disease), ocular and vascular dementias.

• Claim 22 pulls out a narrower but commercially relevant subset: bone osteolysis and/or bone pain using the claimed crystalline Compound I form.

In claim strategy terms, claim 3 is built to support indication-by-indication infringement arguments without needing to prove mechanistic mediation for each listed disease beyond what the claim already prescribes.

How do combination therapy dependent claims expand leverage?

Dependent claims increase settlements and licensing pressure because they attach to specific standard-of-care partners:

• Claim 4: “another therapeutic agent” is any of a wide set spanning chemotherapy, targeted therapies, kinase inhibitors, checkpoint/immune agents (it lists antibody therapy agent generally), and epigenetic and pathway inhibitors. This is broad enough that many add-on regimens can be argued to fall within the list.

• Claim 9: for malignant peripheral nerve sheath tumors, further comprising sirolimus.

• Claims 11 and 15/16: for ovarian cancer and colorectal carcinoma, further comprising paclitaxel and durvalumab, respectively.

This makes the patent useful as a blocker against combination formulations (or combination regimens) even if a challenger argues that monotherapy is defensible via polymorph work.

---

Which diseases and patient populations are explicitly covered by US 10,189,833?

What therapeutic areas are enumerated in claim 3?

Claim 3 lists the following (non-exhaustive as presented):

• CNS / neurodegeneration / neuroinflammation: Alzheimer’s disease, epilepsy, traumatic brain injury, tauopathies, multiple sclerosis, neuro-inflammation, neuroinflammatory disorders, HIV-associated dementia, Binswanger type dementia, dementia with Lewy bodies, progressive supranuclear palsy, dementia subsets (multi infarct, fronto temporal, pseudo-dementia), cerebral palsy, vascular dementias, fronto temporal dementia, pseudo-dementia.

• Ophthalmic: glaucoma, anterior eye disease, posterior eye disease.

• Oncology: non-small cell lung cancer, bladder cancer, ovarian cancer, acute myeloid leukemia, chronic lymphocytic leukemia, breast cancer, cholangiocarcinoma, colon cancer, endometrial cancer, esophageal cancer, glioma, glioblastoma, hepatocellular carcinoma, Hodgkin lymphoma, leukemia, lung cancer, melanoma, mesothelioma, pancreatic cancer, renal cancer, monocytic leukemia, malignant peripheral nerve sheath tumors (MPNST), plexiform neurofibromas, salivary gland tumors (including mucoepidermoid carcinoma and acinic cell carcinoma), gastrointestinal stromal tumors (GIST), giant cell tumors (GCT), pigmented villonodular synovitis (PVNS), tenosynovial giant cell tumor (TGCT).

• Bone / joint: GCT of bone, PVNS, TGCT, and claim 22 adds bone osteolysis/bone pain.

How do claims 5–8 narrow to specific tumor types?

• Claim 5: plexiform neurofibromas.
• Claim 6: tenosynovial giant cell tumor (TGCT).
• Claim 7: pigmented villonodular synovitis (PVNS).
• Claim 8: malignant peripheral nerve sheath tumors (with claim 9 adding sirolimus).

This structure matters for licensing because some of these indications align to existing rare disease commercial strategies where polymorph-specific patents can drive long tail settlements.

---

What patents protect the claimed crystalline Compound I polymorph (and why that matters for infringement)?

How do claims limit “the crystalline form” technologically?

The claimed solid state is defined as:

• “A crystalline form of Compound I”
• characterized by XRPD peaks at 7.3, 23.3, 28.2 (±0.2) 2θ
• measured on a diffractometer using Cu–Kα radiation

That is an objective characterization that can be tested.

What infringement proof typically focuses on for polymorph-defined claims?

In practice, infringement battles tend to concentrate on:

1. Whether the accused product contains the same crystalline form.
2. Whether the peaks match under similar testing conditions.
3. Whether sample prep and measurement settings could shift peak appearance.
4. Whether the accused product is a solid dispersion, tablet, capsule, or lyophilized formulation that may alter observable peaks (co-crystals, comminution effects, carrier effects).

The breadth of claim 2 (composition with excipients) increases risk that reformulation attempts still land in the same crystalline core, if the crystalline identity is retained.

---

When does US Patent 10,189,833 lose exclusivity? What does that imply for generic timing?

No exclusivity timeline can be determined from the claim text alone because patent term depends on:

• filing date / priority (20-year term),
• potential patent term adjustment,
• potential additional exclusivity extensions based on regulatory events,
• terminal disclaimer status,
• continuation and divisional portfolio effects.

Without the bibliographic and regulatory event data for US 10,189,833, a date-specific “when it expires” analysis would be speculative.

---

What is the Orange Book status of US 10,189,833, and which products are most exposed?

Orange Book exposure requires mapping:

• Compound I to an FDA-approved NDA/ANDA/BLA product,
• then linking that product to the patent’s listing(s) and to the specific dosage forms/strengths.

The claims provided do not contain the drug name, NDA/BLA number, or the polymorph’s identity as used in an approved product. Without that linkage, an Orange Book status assessment would be incomplete.

---

How strong is the patent estate for this polymorph? Is it more defensible than typical method-of-use patents?

Structural strength: polymorph fingerprint + broad biological mediation

US 10,189,833’s strength comes from the coupling of:

• A specific crystalline identity (XRPD peaks, measurement method conditions),
• with broad biological targeting language (c-FMS, c-Kit, Flt3 or macrophages/microglia mediation),
• and very broad indication coverage (claim 3).

This is more defensible than a simple method-of-use claim where the only dispute is “what therapeutic mechanism exists.” Here, the accused infringer can still fight on polymorph identity, but if they use the same crystalline form, indication breadth becomes comparatively easier to argue.

Key vulnerability: design-around via different solid form

The primary design-around path is solid-state substitution. If Compound I has multiple known crystalline forms and competitors can select a non-matching form, the claim’s XRPD-limited scope can be avoided.

The breadth of claim 1/2 does not stop design-around because the claims hinge on the crystalline fingerprint, not on a generic “compound” identity alone.

Combination claim exposure depends on regimen and formulation

Dependent claims for sirolimus, paclitaxel, and durvalumab create additional negotiation points, but a challenger can still potentially avoid those dependent claims by:

• using monotherapy timing,
• avoiding the specified combination agent,
• or using different combinations not expressly listed (claim 4 is broad, but it is still constrained to enumerated categories/agents).

---

What generic entry risks exist for crystalline Compound I?

What are the main risk scenarios?

1. Direct polymorph infringement: a generic produces the same XRPD-matching crystalline form and launches for listed indications. Risk is high for methods involving that crystalline material.

2. Solid-form substitution: a generic uses a different polymorph/solvate/hydrate. Risk becomes an XRPD battle rather than a broader method-of-use dispute.

3. Product-form engineering: carriers and excipients may not matter for claim 2 if the crystalline form matches; but if the crystalline form is transformed during manufacturing or storage, a competitor could create a different XRPD signature, avoiding infringement.

Method-of-use patent realities

Even if a generic launches an NDA/ANDA product, method-of-use patents are often enforced via:

• inducement theories (labels, marketing, treating physicians),
• carve-outs by indication,
• or litigation contesting whether the prescribed use falls within claim language.

Claim 3’s listing reduces ambiguity because it names many diseases directly.

---

How do c-Kit/c-FMS/Flt3 and macrophage/microglia mediation language affect claim scope?

The claim is not limited to a single receptor. It explicitly includes:

• c-FMS (CSF1R),
• c-Kit (KIT),
• Flt3 (FLT3),
• and mediation by macrophages or microglia.

That language can be used to argue that a wide range of inflammatory and oncologic pathologies qualify, supporting litigation posture across diverse indications listed in claim 3.

---

What patent litigation affects US 10,189,833?

No litigation docket information is provided in the prompt, and there is no patent number-to-case mapping. A case-specific analysis would require external docket linkage that is not available in the supplied data.

---

Key takeaways

• US 10,189,833’s infringement hook is the crystalline form of Compound I, defined by XRPD peaks at 7.3, 23.3, 28.2 (±0.2) 2θ (Cu-Kα), not merely the underlying molecule.
• Claim 3 provides very wide indication coverage, while dependent claims add leverage for combinations with sirolimus, paclitaxel, and durvalumab and for specific tumors such as TGCT, PVNS, MPNST, plexiform neurofibromas.
• The main design-around is solid-state change: selecting a crystalline form that does not match the defined XRPD fingerprint, or using an amorphous/non-matching hydrate/solvate/co-crystal.
• The patent’s business impact in exclusivity timing, Orange Book listing exposure, and litigation posture cannot be determined from the claim text alone.

---

FAQs

1. Can a competitor avoid US 10,189,833 by switching to a different polymorph of Compound I?
2. Does claim 2 (composition with excipients) create broader infringement risk than claim 1 (method of administering)?
3. How do XRPD test conditions (Cu-Kα, peak picking, sample prep) affect polymorph-defined infringement?
4. If a competitor avoids the dependent combination agent (sirolimus/paclitaxel/durvalumab), can it still infringe under independent claims?
5. How can claim 3’s enumerated disease list be used to support method-of-use enforcement for new indications?

---

References

1. United States Patent 10,189,833. (Claim text provided in prompt).

Details for Patent 10,189,833

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Astrazeneca Uk Ltd	IMFINZI	durvalumab	Injection	761069	May 01, 2017		2037-10-04

International Patent Family for US Patent 10,189,833

Country	Patent Number	Estimated Expiration
South Africa	201708007
World Intellectual Property Organization (WIPO)	2016179412
World Intellectual Property Organization (WIPO)	2016179415
United States of America	10040792
United States of America	10399975