United States Patent 10,028,922: What Do the Claims Actually Cover, and How Dense Is the Ambroxol/Bromhexine-for-Gaucher Patent Territory?

United States Patent 10,028,922 is directed to a single core therapeutic proposition: administering ambroxol or bromhexine (or salts) at a specified oral dosing regimen to enhance lysosomal trafficking of misfolded glucocerebrosidase (GCase) in Gaucher’s Disease. The claims are written in a treatment-method format and expand coverage through (i) specific active ingredients (ambroxol, ambroxol hydrochloride, bromhexine), (ii) concomitant Gaucher standard-of-care (another Gaucher drug, recombinant glucocerebrosidase including imiglucerase), and (iii) GBA1 genotype subsets (a broad list of mutations and specific narrower embodiments for N370S, L444P, and E326K).

The landscape question for investors and competitors is not whether ambroxol and bromhexine exist as known mucolytics with lysosomal/trafficking pharmacology. The landscape question is whether this patent’s specific claim architecture (dose window, “once through four times daily,” lysosomal transport of misfolded GCase, and GBA1 mutation sets) is supported strongly enough by disclosure and positioned well enough against preexisting art, especially prior art on pharmacological chaperones for Gaucher.

1. What Is the Claimed Invention in One Sentence?

The independent claim (Claim 1) claims:

Method of enhancing transport of misfolded GCase to a lysosome in a patient with Gaucher’s Disease
By administering ambroxol or bromhexine (or salts)
At a dose of 250–500 mg
Once, twice, three or four times daily
Where the drug “enhances transport” of misfolded GCase to lysosomes

Dependent claims narrow and extend:

Ambroxol-only (Claim 2) and bromhexine-only (Claim 21)
Concomitant Gaucher therapy (Claims 3, 13, 22)
Concomitant recombinant glucocerebrosidase (Claims 5, 14, 6, 15, 23, 24)
Patient genotype constraints (Claims 7, 16, 8/17/26 mutation lists)
Specific mutation embodiments: N370S, L444P, E326K (Claims 9-11, 18-20, 27-29)

2. Claim Coverage Map: What Each Claim Adds (and What It Doesn’t)

2.1 Independent claim (Claim 1): the “spine”

Claim 1 sets the commercial and legal battleground:

Indication/setting: Gaucher’s Disease patient; enhancement of lysosomal transport of misfolded GCase
Mechanism language: “enhances transport … to the lysosome” (a functional outcome)
Drug scope: ambroxol or bromhexine (and salts)
Dose scope: 250–500 mg
Dosing frequency: once through four times/day

Practical implication: A competitor must avoid this claim by changing at least one mandatory element: drug identity (ambroxol/bromhexine), dosing window, dosing frequency, patient selection, or the asserted functional outcome phrasing. In practice, the hardest design-around is changing the dosing regimen and maintaining the same clinical effect.

2.2 Ingredient-specific claims

Claim 2: ambroxol-only
Claim 12: ambroxol hydrochloride (still ambroxol, but salt form)
Claim 21: bromhexine-only

These are classic “slot-in” dependents. They matter because they:

reduce ambiguity in enforcement (an accused product must clearly match the recited salt/form)
allow a party to argue infringement even if the generic is marketed under a narrower molecular/salt label

2.3 Concomitant therapy claims

Claim 3 and Claim 13/22: patient also administered “another drug for treatment of Gaucher’s Disease”
Claim 5 and Claim 14/23/24: patient also administered recombinant glucocerebrosidase; imiglucerase called out in Claim 6/15/24

This architecture is built to prevent a carve-out based on real-world treatment patterns. Most Gaucher regimens include substrate reduction or enzyme replacement or both. These dependents attempt to make it harder for a defendant to say “the regimen in practice is combination therapy, so the method is not the claimed monotherapy.”

2.4 Genotype-defined claims

Claim 7/16/25: patient has a mutation in the gene encoding beta-glucocerebrosidase (GBA1)
Claim 8/17/26: mutation is selected from a long enumerated set
Claim 9-11/18-20/27-29: narrower embodiments where mutation includes N370S, L444P, E326K

Practical implication:

genotype-specific claims can narrow infringement arguments and reduce prior art risk (if the prior art is general to “misfolded GCase” without genotype)
but if the public domain already teaches pharmacological chaperones for Gaucher without genotype restrictions, genotype specificity may not fully overcome obviousness

2.5 What the claim set omits

Notably absent from the claim text you provided:

any explicit requirement for a biomarker endpoint (e.g., plasma chitotriosidase, CCL18, Lyso-Gb1)
any explicit requirement for a specific formulation route (though dose and frequency strongly imply oral administration in practice)
any explicit requirement for demonstrating lysosomal trafficking beyond the functional language in Claim 1

That absence increases the dependence on how courts interpret functional “enhances transport” language and how the specification supports the asserted mechanism.

3. Critical Legal-Technical Evaluation of Claim Strength

3.1 Functional mechanism language is a double-edged sword

Claim 1 requires that ambroxol/bromhexine “enhances transport of misfolded GCase to the lysosome.” This is:

Strengthening because it aligns with a known chaperone/trafficking hypothesis for misfolded lysosomal enzymes
Risky because functional language can become vulnerable if prior art demonstrates lysosomal effects without the same linkage to misfolded GCase transport, or if the specification does not support a clear causal mechanism at the claimed dose/frequency

3.2 Dose and frequency narrow the universe but also create validity targets

The recited 250–500 mg and once to four times daily can help distinguish from:

lower-dose studies of ambroxol/bromhexine in unrelated indications
regimens outside the narrow window

But those same parameters create obviousness exposure if prior art uses ambroxol or bromhexine in dose ranges overlapping 250–500 mg for lysosomal enzyme trafficking or related chaperone effects.

3.3 Genotype lists: enumerated sets reduce ambiguity but do not automatically solve prior art

The enumerated mutation list is broad and includes:

point mutations (multiple single substitutions, including L444P, N370S, E326K)
splice site mutations
frameshift and deletions
nonsense termination (R359X)

This helps enforcement by giving defendants fewer ways to argue they are outside the target genotype set.

However, novelty and nonobviousness hinge on whether earlier references:

already identified ambroxol/bromhexine (or close analogs) as lysosomal trafficking enhancers for misfolded GCase
already connected those compounds to Gaucher patient subpopulations by GBA1 genotype

If the art is general to Gaucher misfolding and lysosomal trafficking, the mutation enumeration may not prevent an obviousness challenge.

3.4 Dependents around imiglucerase reduce “combination therapy” escape

The inclusion of recombinant glucocerebrosidase, specifically imiglucerase, matters in litigation because it anticipates combination standard-of-care. That reduces the plausibility of an infringement defense based on “the patient also got enzyme replacement.”

4. Patent Landscape: How Crowded Is This Territory?

A fully correct landscape analysis requires identifying:

the issuing and prosecution history of US 10,028,922
the complete claim set with exact wording as granted (including any terminal disclaimer, CIP relationship, or continuations)
the closest cited references, including foreign priority applications
the status of related family members and continuations

Under the constraints here, the necessary bibliographic and citation data is not included in your prompt. Without those, a complete, accurate cross-patent mapping (family members, citing/cited art, and competitor portfolio clustering) cannot be produced without risking fabricated links.

So the actionable landscape takeaways below focus strictly on what can be derived from the claims you provided: the likely competition and prior art centers implied by the claim wording.

5. Landscape Inference From Claim Architecture (Actionable for Competitive Strategy)

5.1 Most likely “prior art buckets” that will be targeted in validity

The claims point directly at three prior art buckets:

Pharmacological chaperones for Gaucher / GBA1 misfolding
- Any earlier disclosures that ambroxol or bromhexine (or their class) improve lysosomal trafficking or stability of mutant GCase
Ambroxol and bromhexine pharmacology in lysosomal systems
- Work showing lysosomal modulation, autophagy/trafficking effects, or enzyme processing changes in lysosomal storage contexts
Combination therapy in Gaucher
- If earlier art already teaches combination regimens with enzyme replacement or other drugs, dependents referencing imiglucerase may not rescue patentability

5.2 How competitors can design around (based on your claim text)

To avoid Claim 1 while targeting the same clinical hypothesis, a competitor would need to:

switch away from ambroxol/bromhexine to a different chaperone/trafficking enhancer, or
use a dosing regimen not within 250–500 mg or not within “once through four times daily” as construed, or
remove the functional claim element by using claims/labeled indications that do not involve “enhances transport of misfolded GCase to a lysosome,” depending on enforcement theory, or
target a patient population outside the recited mutation-defined embodiments (but Claim 1 as written is not genotype-limited)

Because Claim 1 is not limited to specific mutations, genotype restrictions only matter for enforcement under the genotype-dependent claims (Claims 7/8/9-11 and parallel sets). If Claim 1 is enforced, genotype design-around becomes less effective.

5.3 Where the economic threat is concentrated

The economic value is concentrated in two regions of claim scope:

Drug identity + dose window: ambroxol/bromhexine at 250–500 mg with 1–4/day dosing
Functional mechanism: lysosomal transport of misfolded GCase

If competitors can demonstrate that their compound or dosing does not “enhance transport” in the claimed sense, or that their dosing is outside the window, they can mitigate exposure.

6. Claim-by-Claim Quick Legal Map (Infringement & Validity Leverage)

Claim	Covers	Key enforcement hinge	Typical validity exposure hinge
1	Ambroxol or bromhexine (or salts), 250–500 mg, 1–4x/day; lysosomal transport of misfolded GCase in Gaucher	Dose window and functional “enhances transport”	Prior art on chaperone/lysosomal trafficking and overlap dosing
2	Ambroxol only	Drug identity	Same as 1
3	Ambroxol + another Gaucher drug	Combination use	Prior art combination regimens
4	Gaucher disease presence	Indication	Not usually novelty-destroying alone
5	Ambroxol + recombinant glucocerebrosidase	Concomitant enzyme replacement	Prior art combination standards
6	Recombinant is imiglucerase	Specific ERT product	Product-specific prior art
7-8	Genotype-defined subsets	Mutation fit	Whether prior art links these mutations to chaperone response
9-11	N370S, L444P, E326K	Mutation fit	Same
12-20	Ambroxol hydrochloride variants + genotype subsets	Salt identity and dose	Same
21-29	Bromhexine variants + genotype subsets	Drug identity and dose	Same as ambroxol bucket

7. What Matters Most for Business Decisions

7.1 Likely high-value claim sets

Claim 1 is the main asset. It is broad: it captures both ambroxol and bromhexine, and it does not restrict to specific GBA1 mutations.
The genotype dependents are leverage tools for narrower enforcement and for improving claim survival where prior art is less specific.

7.2 Likely litigation target points

Dose window interpretation: 250–500 mg and frequency mapping to real-world dosing
Functional mechanism: proof that “enhances transport of misfolded GCase to the lysosome” is supported by the patent disclosure and aligns with experimental evidence
Combination therapy: whether dependents are vulnerable as obvious in light of routine Gaucher co-therapies

Key Takeaways

US 10,028,922 claims a method using ambroxol or bromhexine (or salts) to enhance lysosomal transport of misfolded GCase in Gaucher’s Disease, with a specific dose range of 250–500 mg and dosing frequency once to four times daily.
The claim set is structured to prevent easy carve-outs via combination therapy (including imiglucerase) and patient genotype subsets (broad mutation enumeration with specific focus on N370S, L444P, E326K).
The main business risk and value hinge on Claim 1, not the genotype dependents, because Claim 1 is not mutation-limited.
The main invalidity and design-around pressure points are (i) overlapping prior art on lysosomal trafficking/chaperoning and (ii) whether those prior art regimens overlap the claimed dose and frequency.

FAQs

Does the patent require a specific delivery route (oral vs other)?
The claim text you provided specifies dose and frequency but does not explicitly recite a route.
Is the invention limited to specific GBA1 mutations?
Claim 1 is not mutation-limited. Mutation limits appear in dependent claims.
Does the patent cover use alongside enzyme replacement therapy?
Yes. Multiple dependents include recombinant glucocerebrosidase and specifically imiglucerase.
What are the practical design-around levers?
Avoid ambroxol/bromhexine, shift dose/frequency outside the recited window, or avoid regimes that can be characterized as enhancing lysosomal transport of misfolded GCase.
Which claim is most important for enforcement?
Claim 1, because it defines the core method and is not limited to a genotype subset.

References

No sources were provided in the prompt, and no patent bibliographic data (publication number, priority dates, prosecution citations, family members, or claim text provenance) was included beyond the numbered claims themselves. Therefore, no inline citations or APA reference list can be generated without fabricating records.

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genzyme Corporation	CEREZYME	imiglucerase	For Injection	020367	May 23, 1994	⤷ Start Trial	2036-07-29
Genzyme Corporation	CEREZYME	imiglucerase	For Injection	020367	September 22, 1999	⤷ Start Trial	2036-07-29
>Applicant	>Tradename	>Biologic Ingredient	>Dosage Form	>BLA	>Approval Date	>Patent No.	>Expiredate

Patent: 10,028,922

Summary for Patent: 10,028,922