Novel Protein A Ligands Enable Milder Elution pH for Affinity Chromatography
Summary
Technische Universität München has filed US Patent Application US20260109738A1 for novel Staphylococcal Protein A ligands for affinity chromatography. The application covers two mutated ligand constructs — a single mutant Z(H18S)4 (histidine-to-serine substitution) and a double mutant Z(H18S, N28A)4 (histidine-to-serine and asparagine-to-alanine substitutions) — compared against the unmutated Z4 sequence used in commercial Protein A stationary phases. Testing reportedly demonstrated a >0.5 pH unit reduction in elution pH and a >30% yield improvement at pH 4.0 step-wise elution for the double mutant versus the wild-type ligand, with no decrease in dynamic binding capacity. The application was filed on October 21, 2025, and published on April 23, 2026.
About this source
USPTO classification C07K covers peptides: short amino-acid chains that form the backbone of antibodies, hormones, vaccines, and increasingly a wider class of therapeutic modalities. Every newly published application in C07K lands in this feed, around 175 a month. Applications publish 18 months after filing, so this feed reveals what antibody engineering groups, vaccine developers, and plant biotech researchers were working on in the prior year and a half. Watch this if you compete in biologics, file freedom-to-operate analyses on antibody drug candidates, scout acquisition targets in vaccine platforms, or track protein-based agricultural biotech filings.
What changed
The patent application discloses two novel Protein A ligand constructs — Z(H18S)4 and Z(H18S, N28A)4 — that introduce point mutations to reduce elution pH in Protein A affinity chromatography. The single mutant substitutes histidine with serine at position 18; the double mutant adds an asparagine-to-alanine substitution at position 28. When coupled to a chromatography support matrix and tested against antibodies and an Fc fusion protein, both mutants demonstrated milder elution pH, averaging more than 0.5 pH units lower than the unmutated Z4 control. The double mutant showed a greater than 30% yield increase at pH 4.0 step-wise elution with no observed reduction in dynamic binding capacity or selectivity. A potential application is noted for pH-sensitive molecules prone to aggregation under acidic conditions.
For biotechnology and pharmaceutical manufacturers using Protein A chromatography for Fc-domain antibody purification, these ligand variants may offer a pathway to reduce product degradation during elution and improve overall yield. Companies developing next-generation capture platforms or seeking to process aggregation-prone molecules should monitor this application's prosecution for potential licensing opportunities or freedom-to-operate considerations.
Archived snapshot
Apr 23, 2026GovPing captured this document from the original source. If the source has since changed or been removed, this is the text as it existed at that time.
POLYPEPTIDES COMPRISING PROTEIN DOMAINS LINKED VIA RIGID AMINO ACID LINKERS
Application US20260109738A1 Kind: A1 Apr 23, 2026
Assignee
Technische Universität München, in Vertretung des Freistaates Bayern
Inventors
Sonja BERENSMEIER, Yasmin Kaveh BAGHBADERANI, Sebastian SCHWAMINGER
Abstract
We describe novel Staphylococcal Protein A ligands that enable milder elution pH for use in affinity chromatography. The change in elution pH is the result of point mutations to the protein sequence. Two novel ligands are investigated in this study. The first, designated Z(H18S)4, represents a histidine to serine substitution single mutation. The second, designated Z(H18S, N28A)4, is a double mutant comprising histidine to serine and asparagine to alanine mutations. Both are compared against the unmutated sequence, designated Z4, which is currently utilized in a commercially available Protein A stationary phase for the purification of molecules containing Fc domains. The ligands are coupled to a chromatography support matrix and tested against a panel of antibodies and an Fc fusion protein for elution pH, dynamic binding capacity, step-wise elution, and capture from clarified culture media. Results demonstrate that the novel ligands result in milder elution pH, on average >0.5 pH units, when tested in a pH gradient. For step-wise elution at pH 4.0, the Z(H18S, N28A)4 ligand showed on average a greater than 30% increase in yield compared to Z4. Importantly, for the antibodies tested the mutations did not result in a decrease in dynamic binding capacity or other desirable attributes such as selectivity. A potential application of the novel ligands is shown with a pH sensitive molecule prone to aggregation under acidic conditions.
CPC Classifications
C07K 14/31 C07K 1/22
Filing Date
2025-10-21
Application No.
19364850
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