When do biologic drug patents expire and when will biosimilars launch?

Comprehensive patent-landscape analysis for US Patent 5,849,535 (pegylated human growth hormone variants with defined amino-acid substitutions)

US 5,849,535 is tightly claim-anchored to (i) a specific set of amino-acid substitutions in human growth hormone (hGH), (ii) pegylation to a defined in-use molecular-weight window (40–100 kDa) with PEG load 4–6 PEG molecules, and (iii) downstream purification by cation-exchange chromatography of the pegylated product. The estate is therefore less about broad “hGH + PEG” coverage and more about blocking direct design-around moves that preserve the defined variant sequence and pegylation regime, including nucleic acid, vector, host cell, and culture/recovery manufacturing claims that track the same sequence.

At a high level, the landscape risk for generic or biosimilar-style entry is not “PEGylation per se.” It is the ability to launch a product that (a) avoids the claimed variant sequence while retaining comparable pharmacology and (b) avoids the pegylation parameters and the chromatography step claimed in claim 2. If a competitor keeps the same variant sequence but changes PEG chemistry, PEG number, target molecular weight, or the purification train, they may still run into claims 3–5 and/or 2 depending on how closely the product process is practiced.

What claims define US 5,849,535’s “core” coverage for hGH variants?

Featured-snippet answer: The patent’s claim center is a narrowly defined hGH variant defined by eight amino-acid substitutions (H18D, H21N, R167N, K168A, D171S, K172R, E174S, I179T), with a dependent branch adding an additional G120 substitution, and with pegylation and cation-exchange chromatography purification steps layered on top.

Claim 1: The sequence lock

Claim 1 defines the “baseline” variant by eight substitution positions. This is the main design-around control point. Any product that uses a materially different variant sequence is, at minimum, not within claim 1 and likely not within the downstream dependent claims that track claim 1.

Business implication: A competitor can potentially avoid the estate by moving off the exact substitution set (including the exact residues/positions). That is often easier than trying to evade pegylation or chromatography claims while keeping the variant biology.

Claims 6–9: The “G120 branch” expands the lock

Claims 6–8 add a ninth substitution at G120, with a specific selection set, including G120K in claims 8 and 9–11 (for the pegylated MW and PEG load dependent constraints).

Risk effect: This creates two “covered” sequence classes:

the eight-substitution variant (claim 1), and
the nine-substitution variant including one of the enumerated G120 substitutions (claim 6–8), with a specific G120K implementation in claims 8–11.

Claims 3–5: Pegylation regime constraints (MW window + PEG count)

Claim 3 constrains actual molecular weight of the pegylated variant to 40–100 kDa.
Claim 4 specifies PEG as the chemical group.
Claim 5 constrains PEG load to 4–6 PEG molecules conjugated.

Business implication: Even if a competitor uses the same amino-acid variant sequence, staying outside the 40–100 kDa window and/or using a PEG count outside 4–6 is a key potential path to non-infringement. In practice, PEG load is difficult to control with absolute certainty at batch scale, so litigation typically turns on measured product specs and whether claim interpretation reads “about” broadly.

Claim 2: A purification-method hook that can trap “process-following” use

Claim 2 is method-of-production for the pegylated variant and recites:

(a) pegylating the hGH variant of claim 1,
(b) applying the pegylated variant to a cation exchange chromatography column,
(c) eluting the pegylated variant.

Business implication: This is a relatively low-tech purification step (common in protein bioprocessing), but the novelty is locked to the claimed starting pegylated sequence. If a manufacturer uses the claimed variant and practices cation-exchange chromatography at any step that is arguably “applying” and “eluting” the pegylated variant, infringement risk rises for process-centric facilities.

Claims 12–22: IP stack covering sequence-to-make chain

The patent contains the typical nucleic acid / vector / host cell / culturing-recovering coverage for the same variant sequences:

claim 12–15 nucleic acids and vectors for the eight-substitution variant and the G120-extended version,
claim 16–17 host cells,
claim 18–19 process preparing the hGH variant by culturing the host cell and recovering the product,
claims 20–22 nucleic acids/vectors/host cells for the H18D, H21N, G120K, plus the rest of the core eight-substitution set (i179T included).

Business implication: The estate is structured to block multiple “entry points” in a manufacturing and tech-transfer lifecycle, not only finished drug composition.

How would a competitor design around US 5,849,535? What are the easiest vs hardest exit ramps?

Featured-snippet answer: The easiest design-around is changing the hGH variant sequence so it no longer contains the exact eight-substitution pattern (and/or the specific G120 substitutions). The hardest is retaining the same variant sequence while escaping pegylation MW/PEG-load limits and avoiding a cation-exchange chromatography step in the pegylated product train.

Design-around vectors ranked by typical practical difficulty

Sequence change (highest leverage):
Replace one or more residues outside the claimed substitution set. This avoids claim 1 directly and collapses most downstream claims that depend on claim 1.
PEG-load and MW shift (middle leverage):
Keep the same sequence but tune pegylation to fall outside 40–100 kDa or outside “4–6 PEG molecules.” The claim language uses “about,” but the measurement is product-defined and will still be attacked with spec evidence.
Purification-train modification (context-dependent):
Avoid cation exchange chromatography for the pegylated variant. Because claim 2 is short and generic (“apply… to a cation exchange chromatography column” and “elute”), a change in purification scheme could help, but it must be real and documented in the commercial process.

Where “partial design-around” can fail

A common failure mode is changing PEG chemistry or linker while keeping pegylated product specs inside the claim window and using cation exchange for the pegylated intermediate. In that scenario, you can still hit claims 3–5 and 2, and still be caught by sequence claims 1/6/8 depending on the exact variant.

What patents cover pegylated human growth hormone variants with specific amino-acid substitutions like H18D/H21N/R167N/K168A/D171S/K172R/E174S/I179T?

Featured-snippet answer: US 5,849,535 is one of the more sequence-specific pegylated-hGH estates. In this field, multiple overlapping patent families typically exist across (i) hGH variants, (ii) PEG conjugation strategies, and (iii) purification and analytical characterization, but US 5,849,535’s sequence specificity narrows its “coverage radius.”

Landscape buckets most relevant to this claim set

hGH variant substitution families
- Sequence libraries that alter stability, receptor interaction, or formulation behavior.
PEGylation conjugate families
- PEG identity, linker chemistry (often amide/labeling strategies), pegylation site strategies, and average PEG loading/MW distributions.
Purification and downstream processing families
- Ion exchange (including cation exchange), chromatography polishing, and conditioning steps.

Practical evaluation approach

For licensing and freedom-to-operate:

map competitor product sequence to the substitution positions (H18D, H21N, R167N, K168A, D171S, K172R, E174S, I179T, plus G120 branch),
then map competitor pegylation specs (actual MW and PEG count) to claims 3–5,
then map the actual downstream process for the pegylated intermediate for cation exchange usage.

When does US 5,849,535 expire? How much exclusivity time remains for generic or biosimilar-style competition?

Featured-snippet answer: A claim-expiration timeline cannot be produced from the information provided because patent term depends on the filing date and any adjustments or maintenance status, none of which are included in the prompt.

What does US 5,849,535 protect that a biosimilar (or generic) would still need to replicate?

Featured-snippet answer: It protects replication of a specific hGH variant sequence and replication of the pegylated product’s MW and PEG loading, plus a cation-exchange chromatography step for the pegylated variant. It also protects nucleic acids, vectors, host cells, and manufacturing by culturing and recovery.

Product vs process risk split

Product claims (3–5) create direct product infringement risk for pegylated conjugates that match sequence and pegylation constraints.
Method claims (2) create process liability risk where manufacturing uses cation exchange chromatography with the pegylated variant.
Manufacturing IP stack (12–22) adds liability around upstream DNA/RNA, vectors, host cell systems, and culturing/recovery.

What a “biosimilar-style” entrant must do to avoid infringement

A biosimilar approach typically seeks to match the active substance. Here, matching the active substance means matching the specific sequence and pegylated configuration. A biosimilar designed around a different variant sequence is the main off-ramp.

Is US 5,849,535 enforceable against “pegylated hGH” broadly, or only pegylated variants that match the claimed amino-acid set?

Featured-snippet answer: The enforceable scope is anchored to the claimed amino-acid substitutions. “Pegylated hGH” generally is not enough; the claims require the specific variant set and, for dependent claims, specific MW and PEG-load constraints.

Claim dependency confirms the limited breadth

Claim 2 depends on claim 1 pegylation and then chromatography.
Claims 3–5 depend on claim 1.
Claims 6–11 depend on claim 1 plus G120 branch.
Claims 12–22 mirror the same sequence dependency.

How strong is the patent estate for US 5,849,535 given its claim structure?

Featured-snippet answer: The patent is strong against “near-copy” designs that keep the claimed variant sequence and remain within the pegylation MW and PEG-load bands. It is weaker against a competitor who substitutes away from the exact residues or moves purification off cation exchange for the pegylated intermediate.

Strength drivers

Exact substitution set (high specificity): reduces prior art overlap if the exact combination is uncommon.
Downstream product specs (MW + PEG count): creates a measurable infringement lever.
Manufacturing IP coverage: nucleic acid/vector/host cell and culturing-recovery claims can support multiple theories.

Weakness drivers

Limited to a defined sequence: competitors can redesign variant residues to exit.
Method claim 2 is generic purification language: if competitors can structure the process to avoid cation exchange or argue the pegylated intermediate is not “applied” in the claimed manner, infringement can narrow.

What claim elements are most likely to be disputed in litigation for US 5,849,535?

Featured-snippet answer: The dispute is most likely around (i) whether the accused product contains the claimed substitution set (including G120 variant identity), (ii) whether measured “actual molecular weight” and PEG count fall within 40–100 kDa and “4–6 molecules of PEG,” and (iii) whether the manufacturing step qualifies as “applying” to a cation exchange chromatography column and “eluting” the pegylated variant.

Element-by-element dispute map

Sequence identity: mass spec sequencing and peptide mapping.
G120 substitution selection: whether substitutions are exactly G120K vs other residues.
Actual molecular weight: which assay, which fraction (heterogeneous PEG distribution), and what “about” covers.
PEG molecule count (4–6): distribution analysis, average vs modal vs spec-based characterization.
Cation exchange step: process flow diagrams, batch records, fraction tracking, and whether the step occurs for the pegylated variant intermediate.

How does US 5,849,535 compare with other pegylated hGH patent estates?

Featured-snippet answer: Compared with broader “PEGylate hGH by any method” patents, US 5,849,535 is more sequence- and spec-bounded. That usually narrows infringement reach but increases leverage in enforcement against direct copies that retain the same variant and pegylation characteristics.

Benchmarking dimensions

Variant breadth: narrow substitution set vs larger libraries.
PEG control: MW window and PEG count vs broader conjugate definitions.
Process claims: presence of a defined downstream chromatography step.

What generic-entry risks exist for US 5,849,535 (ANDA vs 505(b)(2) vs “biosimilar” pathways)?

Featured-snippet answer: Risk exists primarily for products using the claimed variant sequence and matching pegylation parameters. Entry approaches that avoid the variant sequence and change pegylation specs and/or process purification steps reduce risk.

Pathway-specific friction (conceptual)

“Generic” small-molecule logic does not map cleanly to pegylated biologics, but any abbreviated pathway for complex biologics still faces substantial product characterization barriers.
“Biosimilar-style” development faces active substance and structural match requirements, which are exactly where this patent locks in sequence and PEG spec parameters.

What is the Orange Book status of US 5,849,535?

Featured-snippet answer: Orange Book status cannot be determined from the provided information because it depends on listing data, FDA product linkage, and patent-to-product assignments.

Key Takeaways

US 5,849,535 is anchored to an exact hGH variant substitution set (H18D, H21N, R167N, K168A, D171S, K172R, E174S, I179T) with an expansion to G120 substitutions, including G120K.
The patent’s pegylation protection is not open-ended: it requires PEG conjugation to an actual molecular weight of about 40–100 kDa and (when dependent) PEG loading of about 4–6 PEG molecules.
The process claim (pegylate then cation-exchange chromatography and elute) creates risk for manufacturers that use cation exchange for the claimed pegylated intermediate.
The nucleic acid/vector/host cell and culturing/recovery claims extend infringement theories upstream and in manufacturing tech transfer.
Design-around is most feasible through changing the hGH variant sequence. Pegylation-spec and purification-train changes are secondary routes and typically harder to guarantee at scale.

FAQs

What substitution positions in US 5,849,535 are “must-have” for infringement of the variant claims?
If a competitor pegylates the same hGH variant but targets a molecular weight outside 40–100 kDa, does that avoid claims 3–5?
How does the “actual molecular weight” limitation interact with heterogeneous PEG distributions in practice?
Does using cation exchange chromatography for the pegylated intermediate always trigger claim 2, or can process fractionation avoid the “apply and elute” element?
Which upstream activities (nucleic acid, vector, host cell, culturing) can a patent owner use to block technology transfer under US 5,849,535?

References (APA)

United States Patent 5,849,535.

Title:	Human growth hormone variants
Abstract:	Human growth hormone variants, DNA encoding the variants, vectors, host cells, pegylated forms of the variants, as well as methods of making the variants are disclosed.
Inventor(s):	Cunningham; Brian C. (San Bruno, CA), Lowman; Henry B. (Hercules, CA), Wells; James A. (Burlingame, CA), Clark; Ross G. (Pacifica, CA), Olson; Kenneth (Burlingame, CA), Fuh; Germaine G. (Pacifica, CA)
Assignee:	Genentech, Inc. (South San Francisco, CA)
Application Number:	08/717,394
Patent Claims:	see list of patent claims
Patent landscape, scope, and claims summary:	Comprehensive patent-landscape analysis for US Patent 5,849,535 (pegylated human growth hormone variants with defined amino-acid substitutions) US 5,849,535 is tightly claim-anchored to (i) a specific set of amino-acid substitutions in human growth hormone (hGH), (ii) pegylation to a defined in-use molecular-weight window (40–100 kDa) with PEG load 4–6 PEG molecules, and (iii) downstream purification by cation-exchange chromatography of the pegylated product. The estate is therefore less about broad “hGH + PEG” coverage and more about blocking direct design-around moves that preserve the defined variant sequence and pegylation regime, including nucleic acid, vector, host cell, and culture/recovery manufacturing claims that track the same sequence. At a high level, the landscape risk for generic or biosimilar-style entry is not “PEGylation per se.” It is the ability to launch a product that (a) avoids the claimed variant sequence while retaining comparable pharmacology and (b) avoids the pegylation parameters and the chromatography step claimed in claim 2. If a competitor keeps the same variant sequence but changes PEG chemistry, PEG number, target molecular weight, or the purification train, they may still run into claims 3–5 and/or 2 depending on how closely the product process is practiced. What claims define US 5,849,535’s “core” coverage for hGH variants? Featured-snippet answer: The patent’s claim center is a narrowly defined hGH variant defined by eight amino-acid substitutions (H18D, H21N, R167N, K168A, D171S, K172R, E174S, I179T), with a dependent branch adding an additional G120 substitution, and with pegylation and cation-exchange chromatography purification steps layered on top. Claim 1: The sequence lock Claim 1 defines the “baseline” variant by eight substitution positions. This is the main design-around control point. Any product that uses a materially different variant sequence is, at minimum, not within claim 1 and likely not within the downstream dependent claims that track claim 1. Business implication: A competitor can potentially avoid the estate by moving off the exact substitution set (including the exact residues/positions). That is often easier than trying to evade pegylation or chromatography claims while keeping the variant biology. Claims 6–9: The “G120 branch” expands the lock Claims 6–8 add a ninth substitution at G120, with a specific selection set, including G120K in claims 8 and 9–11 (for the pegylated MW and PEG load dependent constraints). Risk effect: This creates two “covered” sequence classes: the eight-substitution variant (claim 1), and the nine-substitution variant including one of the enumerated G120 substitutions (claim 6–8), with a specific G120K implementation in claims 8–11. Claims 3–5: Pegylation regime constraints (MW window + PEG count) Claim 3 constrains actual molecular weight of the pegylated variant to 40–100 kDa. Claim 4 specifies PEG as the chemical group. Claim 5 constrains PEG load to 4–6 PEG molecules conjugated. Business implication: Even if a competitor uses the same amino-acid variant sequence, staying outside the 40–100 kDa window and/or using a PEG count outside 4–6 is a key potential path to non-infringement. In practice, PEG load is difficult to control with absolute certainty at batch scale, so litigation typically turns on measured product specs and whether claim interpretation reads “about” broadly. Claim 2: A purification-method hook that can trap “process-following” use Claim 2 is method-of-production for the pegylated variant and recites: (a) pegylating the hGH variant of claim 1, (b) applying the pegylated variant to a cation exchange chromatography column, (c) eluting the pegylated variant. Business implication: This is a relatively low-tech purification step (common in protein bioprocessing), but the novelty is locked to the claimed starting pegylated sequence. If a manufacturer uses the claimed variant and practices cation-exchange chromatography at any step that is arguably “applying” and “eluting” the pegylated variant, infringement risk rises for process-centric facilities. Claims 12–22: IP stack covering sequence-to-make chain The patent contains the typical nucleic acid / vector / host cell / culturing-recovering coverage for the same variant sequences: claim 12–15 nucleic acids and vectors for the eight-substitution variant and the G120-extended version, claim 16–17 host cells, claim 18–19 process preparing the hGH variant by culturing the host cell and recovering the product, claims 20–22 nucleic acids/vectors/host cells for the H18D, H21N, G120K, plus the rest of the core eight-substitution set (i179T included). Business implication: The estate is structured to block multiple “entry points” in a manufacturing and tech-transfer lifecycle, not only finished drug composition. How would a competitor design around US 5,849,535? What are the easiest vs hardest exit ramps? Featured-snippet answer: The easiest design-around is changing the hGH variant sequence so it no longer contains the exact eight-substitution pattern (and/or the specific G120 substitutions). The hardest is retaining the same variant sequence while escaping pegylation MW/PEG-load limits and avoiding a cation-exchange chromatography step in the pegylated product train. Design-around vectors ranked by typical practical difficulty Sequence change (highest leverage): Replace one or more residues outside the claimed substitution set. This avoids claim 1 directly and collapses most downstream claims that depend on claim 1. PEG-load and MW shift (middle leverage): Keep the same sequence but tune pegylation to fall outside 40–100 kDa or outside “4–6 PEG molecules.” The claim language uses “about,” but the measurement is product-defined and will still be attacked with spec evidence. Purification-train modification (context-dependent): Avoid cation exchange chromatography for the pegylated variant. Because claim 2 is short and generic (“apply… to a cation exchange chromatography column” and “elute”), a change in purification scheme could help, but it must be real and documented in the commercial process. Where “partial design-around” can fail A common failure mode is changing PEG chemistry or linker while keeping pegylated product specs inside the claim window and using cation exchange for the pegylated intermediate. In that scenario, you can still hit claims 3–5 and 2, and still be caught by sequence claims 1/6/8 depending on the exact variant. What patents cover pegylated human growth hormone variants with specific amino-acid substitutions like H18D/H21N/R167N/K168A/D171S/K172R/E174S/I179T? Featured-snippet answer: US 5,849,535 is one of the more sequence-specific pegylated-hGH estates. In this field, multiple overlapping patent families typically exist across (i) hGH variants, (ii) PEG conjugation strategies, and (iii) purification and analytical characterization, but US 5,849,535’s sequence specificity narrows its “coverage radius.” Landscape buckets most relevant to this claim set hGH variant substitution families Sequence libraries that alter stability, receptor interaction, or formulation behavior. PEGylation conjugate families PEG identity, linker chemistry (often amide/labeling strategies), pegylation site strategies, and average PEG loading/MW distributions. Purification and downstream processing families Ion exchange (including cation exchange), chromatography polishing, and conditioning steps. Practical evaluation approach For licensing and freedom-to-operate: map competitor product sequence to the substitution positions (H18D, H21N, R167N, K168A, D171S, K172R, E174S, I179T, plus G120 branch), then map competitor pegylation specs (actual MW and PEG count) to claims 3–5, then map the actual downstream process for the pegylated intermediate for cation exchange usage. When does US 5,849,535 expire? How much exclusivity time remains for generic or biosimilar-style competition? Featured-snippet answer: A claim-expiration timeline cannot be produced from the information provided because patent term depends on the filing date and any adjustments or maintenance status, none of which are included in the prompt. What does US 5,849,535 protect that a biosimilar (or generic) would still need to replicate? Featured-snippet answer: It protects replication of a specific hGH variant sequence and replication of the pegylated product’s MW and PEG loading, plus a cation-exchange chromatography step for the pegylated variant. It also protects nucleic acids, vectors, host cells, and manufacturing by culturing and recovery. Product vs process risk split Product claims (3–5) create direct product infringement risk for pegylated conjugates that match sequence and pegylation constraints. Method claims (2) create process liability risk where manufacturing uses cation exchange chromatography with the pegylated variant. Manufacturing IP stack (12–22) adds liability around upstream DNA/RNA, vectors, host cell systems, and culturing/recovery. What a “biosimilar-style” entrant must do to avoid infringement A biosimilar approach typically seeks to match the active substance. Here, matching the active substance means matching the specific sequence and pegylated configuration. A biosimilar designed around a different variant sequence is the main off-ramp. Is US 5,849,535 enforceable against “pegylated hGH” broadly, or only pegylated variants that match the claimed amino-acid set? Featured-snippet answer: The enforceable scope is anchored to the claimed amino-acid substitutions. “Pegylated hGH” generally is not enough; the claims require the specific variant set and, for dependent claims, specific MW and PEG-load constraints. Claim dependency confirms the limited breadth Claim 2 depends on claim 1 pegylation and then chromatography. Claims 3–5 depend on claim 1. Claims 6–11 depend on claim 1 plus G120 branch. Claims 12–22 mirror the same sequence dependency. How strong is the patent estate for US 5,849,535 given its claim structure? Featured-snippet answer: The patent is strong against “near-copy” designs that keep the claimed variant sequence and remain within the pegylation MW and PEG-load bands. It is weaker against a competitor who substitutes away from the exact residues or moves purification off cation exchange for the pegylated intermediate. Strength drivers Exact substitution set (high specificity): reduces prior art overlap if the exact combination is uncommon. Downstream product specs (MW + PEG count): creates a measurable infringement lever. Manufacturing IP coverage: nucleic acid/vector/host cell and culturing-recovery claims can support multiple theories. Weakness drivers Limited to a defined sequence: competitors can redesign variant residues to exit. Method claim 2 is generic purification language: if competitors can structure the process to avoid cation exchange or argue the pegylated intermediate is not “applied” in the claimed manner, infringement can narrow. What claim elements are most likely to be disputed in litigation for US 5,849,535? Featured-snippet answer: The dispute is most likely around (i) whether the accused product contains the claimed substitution set (including G120 variant identity), (ii) whether measured “actual molecular weight” and PEG count fall within 40–100 kDa and “4–6 molecules of PEG,” and (iii) whether the manufacturing step qualifies as “applying” to a cation exchange chromatography column and “eluting” the pegylated variant. Element-by-element dispute map Sequence identity: mass spec sequencing and peptide mapping. G120 substitution selection: whether substitutions are exactly G120K vs other residues. Actual molecular weight: which assay, which fraction (heterogeneous PEG distribution), and what “about” covers. PEG molecule count (4–6): distribution analysis, average vs modal vs spec-based characterization. Cation exchange step: process flow diagrams, batch records, fraction tracking, and whether the step occurs for the pegylated variant intermediate. How does US 5,849,535 compare with other pegylated hGH patent estates? Featured-snippet answer: Compared with broader “PEGylate hGH by any method” patents, US 5,849,535 is more sequence- and spec-bounded. That usually narrows infringement reach but increases leverage in enforcement against direct copies that retain the same variant and pegylation characteristics. Benchmarking dimensions Variant breadth: narrow substitution set vs larger libraries. PEG control: MW window and PEG count vs broader conjugate definitions. Process claims: presence of a defined downstream chromatography step. What generic-entry risks exist for US 5,849,535 (ANDA vs 505(b)(2) vs “biosimilar” pathways)? Featured-snippet answer: Risk exists primarily for products using the claimed variant sequence and matching pegylation parameters. Entry approaches that avoid the variant sequence and change pegylation specs and/or process purification steps reduce risk. Pathway-specific friction (conceptual) “Generic” small-molecule logic does not map cleanly to pegylated biologics, but any abbreviated pathway for complex biologics still faces substantial product characterization barriers. “Biosimilar-style” development faces active substance and structural match requirements, which are exactly where this patent locks in sequence and PEG spec parameters. What is the Orange Book status of US 5,849,535? Featured-snippet answer: Orange Book status cannot be determined from the provided information because it depends on listing data, FDA product linkage, and patent-to-product assignments. Key Takeaways US 5,849,535 is anchored to an exact hGH variant substitution set (H18D, H21N, R167N, K168A, D171S, K172R, E174S, I179T) with an expansion to G120 substitutions, including G120K. The patent’s pegylation protection is not open-ended: it requires PEG conjugation to an actual molecular weight of about 40–100 kDa and (when dependent) PEG loading of about 4–6 PEG molecules. The process claim (pegylate then cation-exchange chromatography and elute) creates risk for manufacturers that use cation exchange for the claimed pegylated intermediate. The nucleic acid/vector/host cell and culturing/recovery claims extend infringement theories upstream and in manufacturing tech transfer. Design-around is most feasible through changing the hGH variant sequence. Pegylation-spec and purification-train changes are secondary routes and typically harder to guarantee at scale. FAQs What substitution positions in US 5,849,535 are “must-have” for infringement of the variant claims? If a competitor pegylates the same hGH variant but targets a molecular weight outside 40–100 kDa, does that avoid claims 3–5? How does the “actual molecular weight” limitation interact with heterogeneous PEG distributions in practice? Does using cation exchange chromatography for the pegylated intermediate always trigger claim 2, or can process fractionation avoid the “apply and elute” element? Which upstream activities (nucleic acid, vector, host cell, culturing) can a patent owner use to block technology transfer under US 5,849,535? References (APA) United States Patent 5,849,535. More… ↓ ⤷ Start Trial

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Pharmacia & Upjohn Company Llc	SOMAVERT	pegvisomant	For Injection	021106	March 25, 2003	⤷ Start Trial	2016-09-20
Pharmacia & Upjohn Company Llc	SOMAVERT	pegvisomant	For Injection	021106	July 31, 2014	⤷ Start Trial	2016-09-20
>Applicant	>Tradename	>Biologic Ingredient	>Dosage Form	>BLA	>Approval Date	>Patent No.	>Expiredate

Country	Patent Number	Estimated Expiration
Austria	E164395	⤷ Start Trial
Austria	E189526	⤷ Start Trial
Austria	E301196	⤷ Start Trial
Austria	E455171	⤷ Start Trial
Australia	7073396	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration

Patent: 5,849,535

Summary for Patent: 5,849,535