L I F E S C I E N C E S

NittoPhase®HL Solid Support

High Loaded Polymeric Solid Supports for Oligonucleotide Synthesis

A Revolutionary Solid Support with Loading as high as

400 µmol/g for DNA and 250 µmol/g for RNA Synthesis
• Maximal Loading Capacity—Robust design enables maximum
loading capacity on the market, delivering synthesis yields at
unprecedented levels.

• Reduced Oligonucleotide Synthesis Costs­—High loading allows

greater synthesis scale per column volume, resulting in outstanding
per micromole synthesis cost savings.

• Proven Performance in Large Scale Therapeutic Oligonucleotide

Synthesis—NittoPhase®HL has shown excellent results in small
to large scale GMP (up to 900 mmole) synthesis of therapeutic Figure 1. SEM image of NittoPhase®HL Solid
oligonucleotides. Support.

• Superior Flexibility—NittoPhase®HL has been widely applied for

syntheses of RNA, longmers and modified oligonucleotides at higher
Table 1. NittoPhase®HL Solid Support properties.
loadings than ever before.
Properties Characteristics
• Outstanding Quality—NittoPhase®HL is manufactured and loaded in Cross-linked
Polymer Matrix
compliance with ISO9001:2008 quality managment system standards. polystyrene

Functionality Hydroxyl group

• Diversified Product Offering— NittoPhase®HL solid supports are
# of Hydroxyl Group 550 μmol/g
available in a variety of loading levels with all standard deoxy and ribo
Average Particle Size 85 μm
bases, Universal Linker, and a wide range of modified custom linkers.
Average Pore Size 45 nm

Since its launch in 2004, NittoPhase® has become the leading solid support in Dry Volume 2.7 ml/g
the therapeutic oligonucleotide synthesis market, with a strong track record of Optimal Loading Capacity 200-400 μmol/g
proven performance in large scale GMP synthesis.
Swelling Volume
4.0 ml/g
(in acetonitrile)
Kinovate has redefined the boundaries of solid phase oligonucleotide synthesis
with the introduction of NittoPhase®HL High Loading Support, which has Swelling Volume
6.1 ml/g
(in toluene)
superb results at scales as high as 900 mmol.
Leaching None
Improved yields and purities, together with the elevated loading capacities,
undoubtedly empower NittoPhase®HL to offer superior performance at lower unit
cost for oligonucleotide synthesis.
Superior Performance from Lab to Commercial Scale
i) Lab Scale
0.18 * Sequence: 21mer RNA
Table 2. Results of lab scale DNA & RNA oligo synthesis with
Backbone: PO
NittoPhase®HL Solid Support.
0.14 Synthesizer: ÄKTA™ OligoPilot™100
NittoPhase®HL Synthesis Scale Crude Yield Purity Column: 6.3 ml fixed bed column
Sequence
Loading (µmol) (OD260/µmol) (%)

AU260
0.10
T200 RNA 21mer 165 106 79

T250* RNA 21mer 176 99 84 0.06

T350 DNA 20mer 283 128 83

0.02

T400 DNA 20mer 307 135 83

0 5 10 15 20 25 30
UnyLinker™350 DNA 20mer 290 134 83
Minutes

Figure 2. IP-HPLC Trace for NittoPhase®HL T250 RNA synthesis.

ii) Medium Scale

Table 3. Results of mid-scale DNA & highly modified RNA oligo synthesis
0.30 * Sequence: Isis 3-10-3 MOE Gapmer
with NittoPhase®HL Solid Support.
Backbone: PS
0.25
NittoPhase®HL Synthesis Scale Crude Yield Purity Synthesizer: ÄKTA™ OligoPilot™100
Sequence
Loading (mmol) (OD260/µmol) (%) Column: FineLine 35 mm Column
0.20
S 145 79 AU260
Modified250** RNA 21mer 2
AS 142 84 0.15

UnyLinker™330* ‡ DNA 16mer 2 105 83 0.10

UnyLinker™350‡ DNA 20mer 2 101 80 0.05

UnyLinker™400‡ DNA 20mer 2 94 73

** In collaboration with Quark Pharmaceuticals, Inc. 0 5 10 15 20 25
‡ Data Courtesy of Isis Pharmaceuticals, Inc. Minutes
S = Sense strand, AS = Antisense strand
Figure 3. IP-HPLC Trace for NittoPhase®HL UnyLinker™330 DNA synthesis.

iii) Clinical Scale

0.40 * Sequence: Isis 5-10-5 MOE Gapmer
Table 4. Results of clinical-scale DNA & highly modified RNA oligo
Backbone: PS
synthesis with NittoPhase®HL Solid Support.
Synthesizer: ÄKTA™ OligoProcess™
0.30
NittoPhase®HL Synthesis Scale Crude Yield Purity Column: TechniKrom® 60 cm Column
Sequence
Loading (mmol) (OD260/µmol) (%)
AU260

S 151 76 0.20
Modified250*** RNA 21mer 65
AS 136 79
UnyLinker™315‡ DNA 20mer 550 111 86 0.10

UnyLinker™315‡ DNA 20mer 700 112 90

UnyLinker™315*‡ DNA 20mer 900 105 83

0 5 10 15 20 25 30
*** In collaboration with NITTO DENKO Avecia Inc. & Quark Pharmaceuticals, Inc. Minutes
‡ Data Courtesy of Isis Pharmaceuticals, Inc.
S = Sense strand, AS = Antisense strand Figure 4. IP-HPLC Trace for NittoPhase®HL UnyLinker™ DNA synthesis.

For more information, please visit www.kinovate.com or contact [email protected]

NittoPhase® is a trademark of Nitto Denko Corporation and UnyLinker™ is a trademark

of Isis Pharmaceuticals, Inc. © 2015 Kinovate Life Sciences Inc. All rights reserved. The
trademarks mentioned herein are the property of Kinovate Life Sciences Inc., or their
respective owners. Printed in the USA. KLS F001 0415
L I F E S C I E N C E S

Kinovate Life Sciences, Inc. 501 Via del Monte, Oceanside, CA 92058 Phone: +1-866-258-3221 Fax: +1-760-435-7050
www.kinovate.com