Patent: 10,781,261

Summary for Patent: 10,781,261

Title:	Subcutaneous formulations of anti-CD38 antibodies and their uses
Abstract:	The present invention relates to subcutaneous formulations of anti-CD38 antibodies and their uses.
Inventor(s):	Jansson; Richard (Spring House, PA), Kumar; Vineet (Spring House, PA)
Assignee:	JANSSEN BIOTECH, INC. (Horsham, PA)
Application Number:	16/380,994
Patent Claims:	see list of patent claims

Critical Patent Landscape Analysis for US Patent 10,781,261 (Anti-CD38 Antibody + rHuPH20, ~120 mg/mL + 2000 U/mL, SC Formulation)

US 10,781,261 claim set centers on a fixed anti-CD38 IgG1 (variable regions defined by SEQ ID NOs), combined with hyaluronidase rHuPH20 (SEQ ID NO: 22) at a defined concentration ratio, in a subcutaneous, hyaluronidase-enabled delivery formulation. The enforceable claim core is (i) the antibody identity (sequence-defined IgG1) and (ii) the formulation system defined by rHuPH20 plus a specific buffer/tonicity/antioxidant/wetting package (histidine, sorbitol, polysorbate-20, methionine) with pH and often narrow numeric ranges, plus (iii) a CD38+ multiple myeloma SC treatment method using the same composition and optional combination regimens.

What does US 10,781,261 claim, and what is the likely claim “center of gravity”?

Featured snippet answer: The patent claims a subcutaneous pharmaceutical composition and treatment method for CD38-positive multiple myeloma combining an IgG1 anti-CD38 antibody defined by specific variable-region sequences with hyaluronidase rHuPH20 at about 120 mg/mL antibody and about 2000 U/mL hyaluronidase, plus a low-pH formulation system (histidine/sorbitol/PS-20/methionine) at specified concentrations and pH.

How broad is the antibody definition?

The claims are sequence-constrained rather than target-only. They require:

• anti-CD38 antibody is IgG1
• heavy chain variable region sequence is either SEQ ID NO: 4 (claim 1) and/or SEQ ID NO: 12 (claim 3/16)
• light chain variable region sequence is either SEQ ID NO: 5 (claim 1) and/or SEQ ID NO: 13 (claim 3/16)
• Additional claim text indicates the hyaluronidase identity is rHuPH20 (SEQ ID NO: 22)

This structure usually makes the enforceable scope narrower on antibody identity but stronger against non-identical antibodies.

Is the hyaluronidase ratio a key infringement trigger?

Yes. Multiple independent claim types use the same concentration anchors:

• anti-CD38 antibody ~120 mg/mL
• hyaluronidase rHuPH20 ~2000 U/mL

The numeric framing is consistent across composition, method, and unit dosage form claims, suggesting the patent’s practical infringement map focuses on products and generics with the same fixed ratio.

What formulation package is required?

Claims 4–13 and 17–20 lock down a formulation system:

• Histidine: 5–50 mM (claims 4, 17) and specific exemplars at ~10 mM (claims 6, 8–13, 18–19)
• Sorbitol: 50–400 mM (claims 4, 17) and exemplars at 100–300 mM (claims 6–8, 18) and specifically ~300 mM (claims 8–13, 19–20, 28–30)
• Polysorbate-20 (PS-20): 0.01–0.1% w/v (claims 5, 17) with exemplars 0.01, 0.02, 0.04, 0.06% w/v (claims 8–13, 10–12)
• Methionine: 0.1–2.5 mg/mL (claims 5, 17) with exemplars 1 mg/mL or 2 mg/mL (claims 8–13, 19–20, 31)
• pH: multiple exemplars at ~5.5 (claims 9–13, 20) and ~5.6 (claims 8, 19)

From an infringement standpoint, many variants will fall outside literal scope if they change:

• the antibody identity (variable regions),
• the rHuPH20 identity,
• the concentration ratio,
• the buffer excipient system, or
• the pH and exemplified concentration points (especially claims 8–13, 27–31, 35).

Which claim categories drive enforceability: composition, method, or unit dosage?

US 10,781,261 includes three enforcement vectors that are typically used in parallel:

1. Composition claims (claims 1–13, 2–9 are dependent chains; claim 1 is the base)
2. Method of treating (claims 15–26, plus combination therapy dependent claims 21–26)
3. Unit dosage form / container (claims 27–37)

Composition claims: the cleanest “product” target

• Claim 1 is the broadest composition statement:
  • antibody identity + rHuPH20 + concentrations + IgG1 + variable regions.
• Claims 4–13 add the excipient/pH system.

If a defendant’s product differs in any of the specific numeric excipient ranges or pH, that often pushes the claim analysis into doctrine-of-equivalents territory, which is harder to predict. But sequence-defined antibody + rHuPH20 identity + ratio will be strong anchors for literal infringement.

Method claims: what activity triggers liability?

Claim 15 is:

• treating CD38-positive multiple myeloma
• administering subcutaneously
• using the same fixed composition concentration (anti-CD38 ~120 mg/mL + rHuPH20 ~2000 U/mL)
• time sufficient to treat

The dependent claims broaden commercial use patterns:

• combination with second therapeutic agent (claim 21)
• second agent classes include proteasome inhibitors, alkylating agents, and glutamic acid derivatives (claim 22–23)
• corticosteroid addition (claim 24–26)

The method claim set is a litigation posture lever: even if a formulation is reformulated slightly (excipient tweaks), a close match on antibody identity, rHuPH20, concentrations, route, and clinical indication can preserve infringement risk.

Unit dosage form and container claims: downstream manufacturing exposure

Claims 27–32 and 35–37 lock down a product “as filled” configuration:

• antibody concentration ~120 mg/mL (plus variable region sequences)
• rHuPH20 2000 U/mL
• histidine 5–15 mM (often ~10 mM exemplar)
• sorbitol 100–300 mM (often ~300 mM exemplar)
• PS-20 0.01–0.04% w/v (often ~0.04% exemplar)
• methionine 1–2 mg/mL (often 1 mg/mL exemplar)
• pH ~5.5 or ~5.6 (claim 27 and claim 35 provide exemplars)

Container claims (34, 36) add coverage for packaging of the claimed unit dosage formulation.

What formulations are protected by US 10,781,261?

Featured snippet answer: The protected formulations are subcutaneous anti-CD38 IgG1 antibody products combined with rHuPH20 at a fixed concentration level, in a low pH, histidine/sorbitol/PS-20/methionine formulation, with exemplified pH ~5.5–5.6 and PS-20 and methionine at specific concentration bands.

Claim-chart style mapping: key protected parameters

Parameter	Claimed range / exemplar	Claim IDs (examples)	Practical risk zone
Antibody identity	IgG1; heavy VSEQ SEQ ID NO: 4 or 12; light VSEQ SEQ ID NO: 5 or 13	1, 3, 15, 16, 27, 33, 35, 37	Switching to different clone likely avoids literal infringement
rHuPH20 identity	rHuPH20 (SEQ ID NO: 22)	1, 15, 27, 35	Using different hyaluronidase may avoid
Antibody concentration	about 120 mg/mL	1, 15, 27, 35	Deviations change literal coverage; equivalents uncertain
rHuPH20 concentration	about 2000 U/mL	1, 15, 27, 35	Same as above
Histidine	5–50 mM (and ~10 mM exemplar)	4, 17, 6, 8–13, 18, 19	Many reformulations outside 10 mM may avoid exemplars
Sorbitol	50–400 mM; ~100–300 mM; ~300 mM exemplar	4, 17, 6, 18, 19, 20, 28–30	Close match matters for narrower claims
PS-20	0.01–0.1% w/v; exemplars 0.01–0.06%	5, 17, 8–13, 10–12	Many alternative surfactants are design-around candidates
Methionine	0.1–2.5 mg/mL; ~1 or ~2 mg/mL	5, 17, 8–13, 19, 20, 31	Changes may avoid
pH	~5.5 or ~5.6 (exemplars)	8–13, 19, 20	pH shifts can break literal claim paths for some dependents

What is the functional role implied by the formulation set?

The combination of histidine (buffering), sorbitol (tonicity/cryoprotection analogue), PS-20 (surfactant), methionine (oxidation scavenger), and low pH (5.5–5.6 exemplars) points to a stability and viscosity/performance package for subcutaneous administration. Those excipient choices will typically be the main design-around levers, but the strongest literal hook remains the antibody and rHuPH20 identities plus the antibody/rHuPH20 concentrations and route/indication in method claims.

What patents protect CD38 IgG1 anti-CD38 + rHuPH20 subcutaneous delivery more broadly?

US 10,781,261 is one instrument within a likely broader IP ecosystem for:

• anti-CD38 therapeutic antibodies (variable region-defined)
• formulation and device/platform IP for subcutaneous injection systems using rHuPH20
• method-of-use/regimen IP for CD38+ multiple myeloma combinations (proteasome inhibitors, IMiDs, alkylators) and corticosteroids

However, without the bibliographic data for US 10,781,261’s file history and without an Orange Book / global family mapping, no complete, citation-grade landscape of additional patents can be constructed.

When does exclusivity or patent protection for the claimed product expire?

Featured snippet answer: US 10,781,261’s own expiration timing cannot be derived from the claim text alone. A defensible exclusivity timeline requires application filing dates, patent term adjustments, and any regulatory exclusivity tied to an approved anti-CD38 plus rHuPH20 subcutaneous product.

No expiration date analysis can be produced from the provided information.

What is the strength of the patent estate for US 10,781,261 based on claim structure alone?

Strength indicators

• Sequence-defined antibody: narrows infringement arguments against non-identical antibodies.
• Fixed concentration ratio: raises literal infringement specificity.
• Multiple dependent ranges: provides fallback coverage around common formulation exemplars (histidine ~10 mM, sorbitol ~300 mM, PS-20 ~0.01–0.06%, methionine ~1–2 mg/mL, pH ~5.5–5.6).
• Route- and indication-limited method: supports enforcement focused on prescribing/administration patterns for CD38+ MM.

Vulnerability indicators

• If a product uses the same antibody but:
  • employs a different hyaluronidase form,
  • uses different concentration ratios,
  • shifts excipient ranges outside the claimed bands, or
  • uses IV or an alternative route, the defendant may design around multiple literal claim paths.
• The most important commercial design-around risk is swapping the hyaluronidase identity or changing the formulation system enough to exit dependent ranges.

How does US 10,781,261 compare with typical design-around strategies for subcutaneous antibody+hyaluronidase products?

Featured snippet answer: The main design-around levers are changing antibody variable regions (clone identity), changing hyaluronidase identity (not rHuPH20), changing the antibody:rHuPH20 concentration ratio, and moving outside the claimed histidine/sorbitol/PS-20/methionine and pH windows.

Likely “high probability” design-around tactics

• Use a different anti-CD38 antibody clone (not matching SEQ ID NO: 4/5 or 12/13 variable region sequences).
• Use a different hyaluronidase (avoid rHuPH20 SEQ ID NO: 22).
• Adjust concentration of either antibody or hyaluronidase away from the “about” anchors if testing shows a material departure.
• Change PS-20 and methionine concentrations and pH to land outside the dependent exemplars.

These tactics typically erode literal infringement while preserving clinical function through formulation optimization.

What generic entry risks exist for US 10,781,261?

Featured snippet answer: The generic risk profile is concentrated in “copy-closest” products that use the same anti-CD38 antibody sequences, rHuPH20, subcutaneous dosing, and closely matching concentration/formulation parameters. Variants that diverge on sequence-defined antibody identity or rHuPH20 identity materially reduce literal infringement risk.

Because claims are sequence-defined, the most straightforward risk for generics arises when the generic is effectively a biosimilar to the same antibody and uses a matched hyaluronidase system. If the underlying antibody is highly patent-protected, the entry risk may be governed more by antibody estate barriers than by this formulation patent alone. But a formulation-only generic that uses a non-matching antibody would likely not read on the claims.

What patent litigation affects US 10,781,261?

No litigation docket mapping can be produced from the provided input. The claim text is insufficient to identify parties, asserted patents, district courts, or settlement structures.

How would FDA regulatory status intersect with US 10,781,261?

Featured snippet answer: FDA regulatory posture depends on whether the relevant anti-CD38 product is approved as a biological product (likely) and whether a biosimilar route (BLA 351(k)) or ANDA route is available for any component. The claims themselves do not determine regulatory pathway.

The claim set supports a likely use case for a subcutaneous combination antibody + rHuPH20 regimen in CD38+ MM, but no Orange Book/BPD listing or approval timeline is extractable without additional FDA identifiers.

Key claim-level “infringement hotspots” for commercialization or licensing

1. Subcutaneous dosing for CD38+ MM using the claimed composition at about 120 mg/mL anti-CD38 and about 2000 U/mL rHuPH20 (claims 15–16).
2. Formulation composition matching histidine, sorbitol, PS-20, methionine concentration windows and pH ~5.5–5.6 (claims 4–13; 17–20; 27–31; 35).
3. As-filled product in a unit dosage form and packaging (claims 27–36).
4. Combination regimens that include specific classes (proteasome inhibitors, alkylating agents, IMiDs) and corticosteroids (claims 21–26).

Key Takeaways

• US 10,781,261 is built around a sequence-defined IgG1 anti-CD38 antibody plus rHuPH20 at fixed concentration anchors and a low-pH histidine/sorbitol/PS-20/methionine formulation.
• The enforceable scope is most likely to land on products that match (i) antibody variable regions, (ii) rHuPH20 identity, (iii) subcutaneous route, (iv) CD38+ MM indication, and (v) formulation/pH windows.
• The main design-around levers are changing the antibody clone (SEQ ID sequence mismatch), changing the hyaluronidase identity, or reformulating outside claimed excipient/pH bands.
• A complete, date-specific landscape (expiration, Orange Book/BPD status, litigation outcomes, and family strength) cannot be derived from claim text alone.

FAQs

1. Does changing PS-20 from polysorbate-20 to another surfactant avoid literal infringement of US 10,781,261?
   Claims require PS-20 specifically (at defined w/v ranges), so a non-PS-20 formulation can avoid literal read if it exits the claimed concentration and identity constraints.

2. Can a different hyaluronidase avoid US 10,781,261 coverage?
   The claims require rHuPH20 (SEQ ID NO: 22). Using a different hyaluronidase can avoid the rHuPH20 identity limitation.

3. Are the method claims limited to CD38-positive multiple myeloma and subcutaneous administration?
   Yes. Claim 15 requires treating CD38-positive MM and administering subcutaneously.

4. Do the unit dosage form claims require the same pH and excipient ranges as the composition claims?
   They track the formulation system closely and include pH and narrower concentration exemplars (e.g., pH about 5.5–5.6 and specific PS-20/methionine/histidine/sorbitol points).

5. If a product uses the same anti-CD38 antibody but a different antibody concentration than “about 120 mg/mL,” does it avoid?
   The claims use “about,” so literal infringement depends on materiality in measured concentration; moving sufficiently away from the claimed anchor and exemplars is the practical design-around approach.

References

1. United States Patent 10,781,261.

Details for Patent 10,781,261

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Bausch & Lomb Incorporated	VITRASE	hyaluronidase	Injection	021640	May 05, 2004		2039-04-10
Bausch & Lomb Incorporated	VITRASE	hyaluronidase	Injection	021640	December 02, 2004		2039-04-10
Amphastar Pharmaceuticals, Inc.	AMPHADASE	hyaluronidase	Injection	021665	October 26, 2004		2039-04-10
Akorn, Inc.	HYDASE	hyaluronidase	Injection	021716	October 25, 2005		2039-04-10