Patent: 10,227,328

Summary for Patent: 10,227,328

Title:	Heterocyclic compound and pharmaceutical composition comprising same
Abstract:	The present invention relates to a novel heterocyclic compound inhibiting a cyclin-dependent kinase (CDK) and a pharmaceutical composition comprising the same as an effective ingredient. The heterocyclic compound according to the present invention or pharmaceutically acceptable salt thereof can be effectively used in treating or preventing cancers, degenerative brain diseases, etc.
Inventor(s):	Min; Changhee (Daejeon, KR), Oh; Byungkyu (Gyeryong-si, KR), Kim; Yongeun (Daejeon, KR), Park; Changmin (Daejeon, KR)
Assignee:	BEYONDBIO INC. (Daejeon, KR)
Application Number:	15/546,714
Patent Claims:	see list of patent claims

US Patent 10,227,328 landscape: what claims 1-12 cover, how broad the compound and method coverage is, and where infringement risk concentrates

US 10,227,328 claims a large structural genus of nitrogen-containing bicyclic/heteroaryl compounds (formula I) with specific substitution parameters (R1 phenyl/pyridine/pyrimidine; R2=H; R3 defined heteroaryl and amine-bearing substituents). Dependent claims lock in a long, enumerated set of specific members, plus broad downstream coverage via (i) pharmaceutical compositions, (ii) combination regimens across a wide anticancer basket, (iii) combination regimens across a degenerative brain disease basket, and (iv) standalone and combination methods for Alzheimer disease, CDK inhibition, and cancer (colon, lung, glioma, brain cancer), including temozolomide and the Alzheimer/brain-disease list.

What is US Patent 10,227,328 claiming at the core (formula I genus vs. enumerated examples)?

Claim 1 structure: a substitution-parameter “genus” with tight constraints

Claim 1 covers “a compound of formula (I) or pharmaceutically acceptable salt thereof” with the following imposed substitutions:

• Heteroatom ring positions: X is nitrogen, and Y and Z are carbon.
• R1 substituent class: phenyl, pyridine, or pyrimidine, substituted or unsubstituted, with one or more substituents selected from:
  • hydroxy
  • amino
  • halogen
• R2: hydrogen
• R3 substituent class: a pyrimidine core substituted or unsubstituted with one or more of:
  • C1–C6 alkyl
  • tetrahydropyranyl
  • piperidinyl substituted/unsubstituted with C1–C6 alkyl
  • morpholino
  • piperazinyl substituted/unsubstituted with C1–C6 alkyl
  • amino
  • C1–C6 alkylamino
  • halogen

Critical take: claim 1 is a genus claim that is broad at the “R1 and R3 substitution” level, but it is not an open-ended generic: it hard-limits the scaffold to formula I with fixed ring atom identities (X=N; Y/Z=C), fixed R2=H, and defined R1 and R3 substitution chemotypes.

Claim 2 enumerates many specific members (named compounds + salt forms)

Claim 2 depends on claim 1 and lists a very large set of specific structures, including:

• multiple bipyridinyl pyridinols substituted with aminopyrimidyl groups
• multiple halogen and methyl substitutions on the pyrimidine portion
• multiple saturated heterocycle substituents (piperidinyl variants, tetrahydropyranyl/pyran, morpholinyl, dimethylamino, methylpiperazinyl)
• many salts: hydrochloride, oxalate, malonate, sulfate, acetate

Critical take: the inclusion of salts materially expands practical coverage. Even if a competitor selects a different solid form for the same base structure, claim 2’s salt enumeration can create multiple infringement hooks if the same base-member is made/marketed as the claimed salt.

Where infringement risk concentrates

• High risk members: the exact enumerated core structures in claim 2 and their explicitly listed salts.
• Medium risk: any compound that fits the claim 1 genus parameters. The genus-to-infringement path is typically more contested in litigation than the exact-match path because claim construction will require mapping the accused structure to the defined parameter language.

What patents protect the pharmaceutical composition in claim 3 (and what does “composition” add legally)?

Claim 3: compound + pharmaceutically acceptable carrier

Claim 3 covers “a pharmaceutical composition comprising” the claim 1 compound (or salt) plus a carrier.

Critical take: claim 3 is usually not a high-content novelty hook. It mainly:

• ties the compound claims to formulation commercialization,
• supports infringement assertions for marketed drug product presentations,
• can matter for regulatory labeling and product-by-product infringement theories (even when the “active” is the same).

Which combination regimens are claimed (cancer, degenerative brain disease, temozolomide) and why they matter in enforcement?

Claim 4: anticancer combination basket

Claim 4 recites that the compound is administered with one or more anticancer agents from a long list covering:

• nucleosides/antimetabolites (capecitabine, 5-FU, thioguanine, gemcitabine, 5-FU analogs)
• platinum agents (oxaliplatin, cisplatin, carboplatin)
• microtubule inhibitors (paclitaxel, docetaxel, vinorelbine, vinblastine, vincristine)
• topoisomerase and related agents (irinotecan, etoposide, topotecan)
• alkylating agents/cytotoxics (cyclophosphamide, iphosphamide, mitomycin C, mechlorethamine, thiotepa, bleomycin, bendamustine, procarbazine, lomustine)
• hormone agents (tamoxifen, anastrozole, exemestane, fulvestrant, megestrol, toremifene)
• targeted kinase inhibitors and immunotherapies (erlotinib, gefitinib, sorafenib, lapatinib, palbociclib, regorafenib, imatinib, sunitinib, axitinib, pazopanib, apatinib, ceritinib, crizotinib, osimertinib, bosutinib, dasatinib, nilotinib, ponatinib)
• monoclonal antibodies and pathway inhibitors (trastuzumab, bevacizumab, cetuximab, aflibercept, pertuzumab, ramucirumab, panitumumab, nivolumab, necitumumab, pembrolizumab, obinutuzumab, ofatumumab)

Critical take: this is a broad “one or more” combination claim over an extremely large therapeutic list. If an accused compound is administered alongside any single listed anticancer agent, the claim language can be satisfied.

Claim 5: degenerative brain disease combination basket

Claim 5 recites combination with one or more drugs selected from:

• levodopa
• dopamine agonists: bromocriptine, ropinirole, rotigotine
• anticholinergics: trihexyphenidyl, benztropine, procyclidine
• COMT inhibitor: entacapone
• MAO-B inhibitor: selegiline, rasagiline
• amantadine, tetrabenazine
• Alzheimer symptomatic agents: donepezil, rivastigmine, galantamine
• NMDA antagonist: memantine

Critical take: claim 5 similarly sets up combination-based infringement theories even if the accused drug is positioned in Parkinson’s spectrum or Alzheimer symptomatic regimens.

Claim 6: explicit temozolomide combination

Claim 6 is a narrow dependent combination:

• compound + temozolomide

Critical take: explicit temozolomide combination is often litigation-relevant because temozolomide is a standard-of-care reference point and can be easily documented in treatment protocols.

What method claims cover (Alzheimer, CDK inhibition, cancer) and how broad is the clinical indication language?

Claim 7: method for treating Alzheimer disease

Claim 7 covers a method of treating Alzheimer disease in a subject by administering the claimed composition (claim 1 compound/salt).

Critical take: the claim is indication-based. The key enforcement lever is whether the accused product is used for Alzheimer treatment (labeling, marketing, and practice evidence can matter).

Claim 8: method for inhibiting CDK

Claim 8 covers:

• method for inhibiting a cyclin dependent kinase (CDK) in a subject
• by administering the composition

Critical take: this is pharmacodynamic/target-activity language, which can support infringement theories where indication labeling is generic but biological activity is demonstrated and asserted.

Claim 9: method for treating cancer with defined cancer list

Claim 9 covers treating cancer by administering the claimed composition, where cancer is selected from:

• colon cancer
• lung cancer
• glioma
• brain cancer

Critical take: unlike a broad “any cancer” method, claim 9 restricts the indication to four categories, increasing the evidentiary specificity of method infringement.

Claims 10-12: combination overlays

• Claim 10: claim 9 method plus additional anticancer agent(s) from the same extensive basket as claim 4.
• Claim 11: claim 9 method plus temozolomide.
• Claim 12: method of claim 6 plus one or more brain disease drugs from the claim 5 list.

Critical take: these stacked combination method claims create multiple parallel infringement routes depending on what concomitant therapies are used in practice.

How strong is the patent estate for US 10,227,328 based on claim scope alone?

Strengths

1. Claim 1 genus is parameterized but chemically meaningful: fixed scaffold atoms (X=N; Y/Z=C), fixed R2 (H), and defined R1/R3 substitution repertoires create a defined infringement perimeter rather than a fully open chemical formula.
2. Claim 2 enumerates many specific structures and salts: this reduces dependence on genus claim construction for a large fraction of possible accused variants.
3. Method claims are indication-anchored and target-anchored: Alzheimer, CDK inhibition, and a cancer list provide multiple angles for asserting usage and pharmacology.
4. Combination claims are extremely broad: the anticancer and brain-disease baskets are large enough that many real-world regimens plausibly intersect with “one or more” listed agents.

Weaknesses / litigation pressure points

1. Genus validity/construction is likely contested: broad substitution language can face challenges if prior art discloses overlapping chemotypes.
2. Claim 2’s practical enforceability depends on exact member mapping: if competitors avoid the enumerated structures and sell only different genus members, litigating claim 1 scope becomes central.
3. Combination-method infringement is fact intensive: enforcement depends on what is prescribed/administered together, and where evidence can tie the accused compound to “administered in combination with” the enumerated agents.

What does this mean for generic or “biosimilar-type” risk?

This is a small molecule patent landscape (chemical genus and salts; no biologic). Competitive risk scenarios focus on:

• Exact-salt/carrier copying: if a challenger selects one of the explicitly enumerated salts (claim 2), infringement is direct.
• Structural design-around: avoiding the enumerated members while landing within the claim 1 substitution parameters creates a more complex infringement posture.
• Indication and regimen carveouts: if a competitor avoids clinical use in Alzheimer/CDK inhibition/cancer indications and avoids concomitant regimens matching the combination lists, method infringement leverage can weaken. Compound infringement for claim 1/2 and composition infringement for claim 3 can still remain even if method evidence is harder.

Key Takeaways

• US 10,227,328 is built around a defined chemical genus (claim 1) plus a very large enumerated list of specific compounds and salts (claim 2).
• The patent then expands into downstream IP coverage: formulations (claim 3), broad anticancer combinations (claims 4, 10), broad degenerative brain disease combinations (claim 5, 12), and indication and mechanism methods (claims 7-9, 11).
• Practical infringement risk concentrates on:
  • sold products using enumerated members/salts in claim 2, and
  • treatment protocols using the claimed compound together with any one listed combination agent.

FAQs

1. Do claim 2 salts expand coverage beyond the freebase compound?
   Yes. Claim 2 enumerates multiple salts (e.g., hydrochloride, oxalate, malonate, sulfate, acetate). A product using a listed salt of an enumerated base structure has a direct claim mapping path.

2. Is the cancer method claim limited to one indication or multiple?
   It is limited to cancers selected from four categories: colon, lung, glioma, and brain cancer.

3. Can a competitor avoid method claims by using the drug only for a non-listed cancer?
   Method claim 9 is limited to the four cancer categories, so off-list indications reduce method-fit. But compound/composition claims can still support infringement.

4. Does claim 8 require proving Alzheimer disease?
   No. Claim 8 is a CDK inhibition method claim. It can be asserted based on the compound’s CDK inhibitory activity in the treated subject.

5. How important is temozolomide in this patent?
   Temozolomide is explicitly named in claim 6 (composition combination) and claim 11 (method combination), creating a clean evidence target in oncology regimens.

References

1. United States Patent 10,227,328 (claims 1-12), as provided in the user prompt.

Details for Patent 10,227,328

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Iovance Biotherapeutics Manufacturing Llc	PROLEUKIN	aldesleukin	For Injection	103293	May 05, 1992	10,227,328	2036-02-02
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	September 25, 1998	10,227,328	2036-02-02
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	February 10, 2017	10,227,328	2036-02-02
Eli Lilly And Company	ERBITUX	cetuximab	Injection	125084	February 12, 2004	10,227,328	2036-02-02