IP Library › Granted Patent US 12,281,137
Granted Patent B2
US 12,281,137 · App. 18/112,952 · Granted Apr 22, 2025

Method for the site-specific enzymatic labelling of nucleic acids in vitro by incorporation of unnatural nucleotides

Inventors: Floyd E. Romesberg (La Jolla, CA); Denis A. Malyshev (Solana Beach, CA); Lingjun Li (San Diego, CA); Thomas Lavergne (Le Versoud, FR); Zhengtao Li (Pudong new district, CN)
Assignee: The Scripps Research Institute
C07H19/24C07H19/00C07H21/00C07H21/04C12N9/22C12N15/1024C12P19/34C12Q1/6832
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,281,137
App. No.
18/112,952
Granted
Apr 22, 2025
Kind
B2
Abstract

Provided herein are analogs of unnatural nucleotides bearing predominantly hydrophobic nucleobase analogs that form unnatural base pairs during DNA polymerase-mediated replication of DNA or RNA polymerase-mediated transcription of RNA. In this manner, the unnatural nucleobases can be introduced in a site-specific way into oligonucleotides (single or double stranded DNA or RNA), where they can provide for site-specific cleavage, or can provide a reactive linker than can undergo functionalization with a cargo-bearing reagent by means of reaction with a primary amino group or by means of click chemistry with an alkyne group of the unnatural nucleobase linker.

Claims (50)

1. A nucleobase pair comprising a first nucleobase analog having the structure β9b, and a second nucleobase analog having any of the structures α15a or α15b:

wherein each X is independently carbon or nitrogen,

wherein each R 1 is independently hydrogen, alkyl group, a reactive linker comprising a reactive center a linker coupled to a cargo,

wherein each R 2 is optional and when present is independently hydrogen, alkyl, alkenyl, alkynyl, methoxy, methanethiol, methaneseleno, halogen, cyano, azide, nitro group, a reactive linker comprising a reactive center, or a linker coupled to a cargo,

wherein each Y is independently sulfur, oxygen, selenium, or a secondary amine,

wherein each E is independently oxygen, sulfur or selenium,

and the wavy line indicates a point of bonding to a ribosyl, deoxyribosyl, or dideoxyribosyl moiety or an analog thereof, wherein the ribosyl, deoxyribosyl, or dideoxyribosyl moiety, or analog thereof is in free form, is bound to a mono-phosphate, diphosphate, triphosphate, α-thiotriphosphate, β-thiophosphate, or γ-thiophosphate group, or is included in an RNA or a DNA or in an RNA analog or a DNA analog.

2. A double-stranded oligonucleotide comprising the nucleobase pair of claim 1 .

3. The nucleobase pair of claim 1 , wherein the ribosyl, deoxyribosyl, or dideoxyribosyl moiety or analog thereof is included in an RNA.

4. The nucleobase pair of claim 1 , wherein the ribosyl, deoxyribosyl, or dideoxyribosyl moiety or analog thereof is included in a DNA.

5. The nucleobase pair of claim 1 , wherein each X in structure β9b is carbon.

6. The nucleobase pair of claim 1 , wherein each R 2 in structure β9b is hydrogen.

7. The nucleobase pair of claim 1 , wherein Y is sulfur.

8. The nucleobase pair of claim 7 , wherein E in structure β9b is sulfur.

9. The nucleobase pair of claim 1 , wherein the first nucleobase analog is

10. The nucleobase pair of claim 1 , wherein the first nucleobase analog is

11. The nucleobase pair of claim 1 , wherein each X in structure α15b and α15a is carbon.

12. The nucleobase pair of claim 1 , wherein the second nucleobase analog has the structure α15b.

13. The nucleobase pair of claim 12 , wherein R 1 in structure α15b is methyl.

14. The nucleobase pair of claim 13 , wherein E in structure α15b is oxygen.

15. The nucleobase pair of claim 12 , wherein each R 2 in structure α15b is hydrogen.

16. The nucleobase pair of claim 12 , wherein the second nucleobase analog is

17. The nucleobase pair of claim 1 , wherein the second nucleobase analog has the structure α15a.

18. The nucleobase pair of claim 17 , wherein at least one R 2 is CN.

19. The nucleobase pair of claim 17 , wherein R 1 in structure α15a is methyl.

20. The nucleobase pair of claim 19 , wherein E in structure α15a is oxygen.

21. The nucleobase pair of claim 17 , wherein the second nucleobase analog is

22. The nucleobase pair of claim 1 , wherein the second nucleobase analog has any of the structures

wherein each R is independently hydrogen, or the reactive linker.

23. The nucleobase pair of claim 1 , wherein the first nucleobase analog is

24. The nucleobase pair of claim 23 , wherein the second nucleobase analog is

25. The nucleobase pair of claim 1 , wherein the first nucleobase analog is

and the second nucleobase analog is

26. The nucleobase pair of claim 1 , wherein the first nucleobase analog is

and the second nucleobase analog is

27. The nucleobase pair of claim 1 , wherein the first nucleobase analog is

and the second nucleobase analog is

28. The nucleobase pair of claim 1, 7, or 8 , wherein at least one R 2 in structure β9b is halogen.

29. The nucleobase pair of claim 8 , wherein each X in structure β9b is carbon.

30. The nucleobase pair of claim 1 , wherein the first nucleobase analog is

31. The nucleobase pair of claim 1 , wherein the first nucleobase analog is

and the second nucleobase analog is

32. A nucleobase pair comprising a first nucleobase analog having the structure

and a second nucleobase analog having the structure

wherein the wavy line indicates a point of bonding to a ribosyl, deoxyribosyl, or dideoxyribosyl moiety, wherein the ribosyl, deoxyribosyl, or dideoxyribosyl moiety (i) has its 5′-hydroxy group in free form or bound to a mono-phosphate, diphosphate, triphosphate, α-thiotriphosphate, β-thiophosphate, γ-thiophosphate group, or (ii) is included in an RNA or a DNA.

33. A nucleobase pair comprising a first nucleobase analog having the structure

and a second nucleobase analog having the structure

wherein the wavy line indicates a point of bonding to a ribosyl, deoxyribosyl, or dideoxyribosyl moiety, wherein the ribosyl, deoxyribosyl, or dideoxyribosyl moiety (i) has its 5′-hydroxy group in free form or bound to a mono-phosphate, diphosphate, triphosphate, α-thiotriphosphate, β-thiophosphate, or γ-thiophosphate group, or (ii) is included in an RNA or a DNA.

34. A double-stranded oligonucleotide comprising the nucleobase pair of claim 32 .

35. A double-stranded oligonucleotide comprising the nucleobase pair of claim 33 .

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 22, 2023
From: ROMESBERG, FLOYD E.; MALYSHEV, DENIS A.; LI, LINGJUN; LAVERGNE, THOMAS; LI, ZHENGTAO
To: THE SCRIPPS RESEARCH INSTITUTE
Reel/Frame 062773/0013 →
Continuity (4)
Division 16518715 · Jul 22, 2019
Division 14910203
Provisional Application 61863649 · Aug 8, 2013
Related Publication 20240101590A1 · Mar 28, 2024
References Cited (400)
US 3687808A · Merigan, Jr. et al. · 1972 [cited by applicant]
US 4469863A · Ts'o et al. · 1984 [cited by applicant]
US 4476301A · Imbach et al. · 1984 [cited by applicant]
US 4587044A · Miller et al. · 1986 [cited by applicant]
US 4605735A · Miyoshi et al. · 1986 [cited by applicant]
US 4667025A · Miyoshi et al. · 1987 [cited by applicant]
US 4762779A · Snitman · 1988 [cited by applicant]
US 4789737A · Miyoshi et al. · 1988 [cited by applicant]
US 4824941A · Gordon et al. · 1989 [cited by applicant]
US 4828979A · Klevan et al. · 1989 [cited by applicant]
US 4835263A · Nguyen et al. · 1989 [cited by applicant]
US 4845205A · Huynh et al. · 1989 [cited by applicant]
US 4849513A · Smith et al. · 1989 [cited by applicant]
US 4876335A · Yamane et al. · 1989 [cited by applicant]
US 4904582A · Tullis · 1990 [cited by applicant]
US 4910300A · Urdea et al. · 1990 [cited by applicant]
US 4948882A · Ruth · 1990 [cited by applicant]
US 4958013A · Letsinger · 1990 [cited by applicant]
US 4981957A · Lebleu et al. · 1991 [cited by applicant]
US 5015733A · Smith et al. · 1991 [cited by applicant]
US 5023243A · Tullis · 1991 [cited by applicant]
US 5034506A · Summerton et al. · 1991 [cited by applicant]
US 5036066A · Fischer et al. · 1991 [cited by applicant]
US 5082830A · Brakel et al. · 1992 [cited by applicant]
US 5093232A · Urdea et al. · 1992 [cited by applicant]
US 5109124A · Ramachandran et al. · 1992 [cited by applicant]
US 5112963A · Pieles et al. · 1992 [cited by applicant]
US 5118800A · Smith et al. · 1992 [cited by applicant]
US 5118802A · Smith et al. · 1992 [cited by applicant]
US 5130302A · Spielvogel et al. · 1992 [cited by applicant]
US 5134066A · Rogers et al. · 1992 [cited by applicant]
US 5138045A · Cook et al. · 1992 [cited by applicant]
US 5166315A · Summerton et al. · 1992 [cited by applicant]
US 5175273A · Bischofberger et al. · 1992 [cited by applicant]
US 5177196A · Meyer, Jr. et al. · 1993 [cited by applicant]
US 5185444A · Summerton et al. · 1993 [cited by applicant]
US 5188897A · Suhadolnik et al. · 1993 [cited by applicant]
US 5214134A · Weis et al. · 1993 [cited by applicant]
US 5214136A · Lin et al. · 1993 [cited by applicant]
US 5216141A · Benner · 1993 [cited by applicant]
US 5218105A · Cook et al. · 1993 [cited by applicant]
US 5235033A · Summerton et al. · 1993 [cited by applicant]
US 5245022A · Weis et al. · 1993 [cited by applicant]
US 5254469A · Warren, III et al. · 1993 [cited by applicant]
US 5258506A · Urdea et al. · 1993 [cited by applicant]
US 5262536A · Hobbs, Jr. · 1993 [cited by applicant]
US 5264423A · Cohen et al. · 1993 [cited by applicant]
US 5264562A · Matteucci · 1993 [cited by applicant]
US 5264564A · Matteucci · 1993 [cited by applicant]
US 5272250A · Spielvogel et al. · 1993 [cited by applicant]
US 5276019A · Cohen et al. · 1994 [cited by applicant]
US 5278302A · Caruthers et al. · 1994 [cited by applicant]
US 5286717A · Cohen et al. · 1994 [cited by applicant]
US 5292873A · Rokita et al. · 1994 [cited by applicant]
US 5317098A · Shizuya et al. · 1994 [cited by applicant]
US 5319080A · Leumann · 1994 [cited by applicant]
US 5321131A · Agrawal et al. · 1994 [cited by applicant]
US 5359044A · Cook et al. · 1994 [cited by applicant]
US 5367066A · Urdea et al. · 1994 [cited by applicant]
US 5371241A · Brush · 1994 [cited by applicant]
US 5391723A · Priest · 1995 [cited by applicant]
US 5393878A · Leumann · 1995 [cited by applicant]
US 5399676A · Froehler · 1995 [cited by applicant]
US 5405938A · Summerton et al. · 1995 [cited by applicant]
US 5405939A · Suhadolnik et al. · 1995 [cited by applicant]
US 5414077A · Lin et al. · 1995 [cited by applicant]
US 5416203A · Letsinger · 1995 [cited by applicant]
US 5432272A · Benner · 1995 [cited by applicant]
US 5434257A · Matteucci et al. · 1995 [cited by applicant]
US 5446137A · Maag et al. · 1995 [cited by applicant]
US 5451463A · Nelson et al. · 1995 [cited by applicant]
US 5453496A · Caruthers et al. · 1995 [cited by applicant]
US 5455233A · Spielvogel et al. · 1995 [cited by applicant]
US 5457187A · Gmeiner et al. · 1995 [cited by applicant]
US 5459255A · Cook et al. · 1995 [cited by applicant]
US 5466677A · Baxter et al. · 1995 [cited by applicant]
US 5466786A · Buhr et al. · 1995 [cited by applicant]
US 5470967A · Huie et al. · 1995 [cited by applicant]
US 5476925A · Letsinger et al. · 1995 [cited by applicant]
US 5484908A · Froehler et al. · 1996 [cited by applicant]
US 5486603A · Buhr · 1996 [cited by applicant]
US 5489677A · Sanghvi et al. · 1996 [cited by applicant]
US 5502177A · Matteucci et al. · 1996 [cited by applicant]
US 5510475A · Agrawal et al. · 1996 [cited by applicant]
US 5512439A · Hornes et al. · 1996 [cited by applicant]
US 5512667A · Reed et al. · 1996 [cited by applicant]
US 5514785A · Van Ness et al. · 1996 [cited by applicant]
US 5519126A · Hecht · 1996 [cited by applicant]
US 5519134A · Acevedo et al. · 1996 [cited by applicant]
US 5525465A · Haralambidis et al. · 1996 [cited by applicant]
US 5525711A · Hawkins et al. · 1996 [cited by applicant]
US 5536821A · Agrawal et al. · 1996 [cited by applicant]
US 5539082A · Nielsen et al. · 1996 [cited by applicant]
US 5541306A · Agrawal et al. · 1996 [cited by applicant]
US 5541307A · Cook et al. · 1996 [cited by applicant]
US 5541313A · Ruth · 1996 [cited by applicant]
US 5545730A · Urdea et al. · 1996 [cited by applicant]
US 5550111A · Suhadolnik et al. · 1996 [cited by applicant]
US 5552538A · Urdea et al. · 1996 [cited by applicant]
US 5552540A · Haralambidis · 1996 [cited by applicant]
US 5561225A · Maddry et al. · 1996 [cited by applicant]
US 5563253A · Agrawal et al. · 1996 [cited by applicant]
US 5565552A · Magda et al. · 1996 [cited by applicant]
US 5567810A · Weis et al. · 1996 [cited by applicant]
US 5567811A · Misiura et al. · 1996 [cited by applicant]
US 5571799A · Tkachuk et al. · 1996 [cited by applicant]
US 5574142A · Meyer, Jr. et al. · 1996 [cited by applicant]
US 5576427A · Cook et al. · 1996 [cited by applicant]
US 5578717A · Urdea et al. · 1996 [cited by applicant]
US 5578718A · Cook et al. · 1996 [cited by applicant]
US 5580731A · Chang et al. · 1996 [cited by applicant]
US 5585481A · Arnold, Jr. et al. · 1996 [cited by applicant]
US 5587361A · Cook et al. · 1996 [cited by applicant]
US 5587371A · Sessler et al. · 1996 [cited by applicant]
US 5587469A · Cook et al. · 1996 [cited by applicant]
US 5591584A · Chang et al. · 1997 [cited by applicant]
US 5591722A · Montgomery et al. · 1997 [cited by applicant]
US 5594121A · Froehler et al. · 1997 [cited by applicant]
US 5595726A · Magda et al. · 1997 [cited by applicant]
US 5595899A · Sato et al. · 1997 [cited by applicant]
US 5596086A · Matteucci et al. · 1997 [cited by applicant]
US 5596091A · Switzer · 1997 [cited by applicant]
US 5597696A · Linn et al. · 1997 [cited by applicant]
US 5597909A · Urdea et al. · 1997 [cited by applicant]
US 5599923A · Sessler et al. · 1997 [cited by applicant]
US 5599928A · Hemmi et al. · 1997 [cited by applicant]
US 5602240A · De Mesmaeker et al. · 1997 [cited by applicant]
US 5608046A · Cook et al. · 1997 [cited by applicant]
US 5610289A · Cook et al. · 1997 [cited by applicant]
US 5610300A · Altmann et al. · 1997 [cited by applicant]
US 5614617A · Cook et al. · 1997 [cited by applicant]
US 5618704A · Sanghvi et al. · 1997 [cited by applicant]
US 5623070A · Cook et al. · 1997 [cited by applicant]
US 5625050A · Beaton et al. · 1997 [cited by applicant]
US 5627053A · Usman et al. · 1997 [cited by applicant]
US 5633360A · Bischofberger et al. · 1997 [cited by applicant]
US 5639873A · Barascut et al. · 1997 [cited by applicant]
US 5645985A · Froehler et al. · 1997 [cited by applicant]
US 5646265A · McGee · 1997 [cited by applicant]
US 5648247A · Picataggio et al. · 1997 [cited by applicant]
US 5658873A · Bertsch-Frank et al. · 1997 [cited by applicant]
US 5663312A · Chaturvedula · 1997 [cited by applicant]
US 5670633A · Cook et al. · 1997 [cited by applicant]
US 5677437A · Teng et al. · 1997 [cited by applicant]
US 5677439A · Weis et al. · 1997 [cited by applicant]
US 5681941A · Cook et al. · 1997 [cited by applicant]
US 5688941A · Cook et al. · 1997 [cited by applicant]
US 5700920A · Altmann et al. · 1997 [cited by applicant]
US 5714331A · Buchardt et al. · 1998 [cited by applicant]
US 5719262A · Buchardt et al. · 1998 [cited by applicant]
US 5750692A · Cook et al. · 1998 [cited by applicant]
US 5763588A · Matteucci et al. · 1998 [cited by applicant]
US 5830653A · Froehler et al. · 1998 [cited by applicant]
US 6005096A · Matteucci et al. · 1999 [cited by applicant]
US 6268490B1 · Imanishi et al. · 2001 [cited by applicant]
US 6525191B1 · Ramasamy · 2003 [cited by applicant]
US 6670461B1 · Wengel et al. · 2003 [cited by applicant]
US 6770748B2 · Imanishi et al. · 2004 [cited by applicant]
US 6794499B2 · Wengel et al. · 2004 [cited by applicant]
US 6955807B1 · Shanafelt et al. · 2005 [cited by applicant]
US 7034133B2 · Wengel et al. · 2006 [cited by applicant]
US 7053207B2 · Wengel · 2006 [cited by applicant]
US 7399845B2 · Seth et al. · 2008 [cited by applicant]
US 7427672B2 · Imanishi et al. · 2008 [cited by applicant]
US 7718374B2 · Belousov et al. · 2010 [cited by applicant]
US 8383792B2 · Okamoto et al. · 2013 [cited by applicant]
US 8501805B2 · Seth et al. · 2013 [cited by applicant]
US 8546556B2 · Seth et al. · 2013 [cited by applicant]
US 10626138B2 · Romesberg et al. · 2020 [cited by applicant]
US 10696719B2 · Romesberg et al. · 2020 [cited by applicant]
US 10696720B2 · Romesberg et al. · 2020 [cited by applicant]
US 11466279B2 · Romesberg et al. · 2022 [cited by applicant]
US 11634451B2 · Romesberg et al. · 2023 [cited by applicant]
US 11879145B2 · Romesberg · 2024 [cited by examiner]
US 20040171570A1 · Allerson et al. · 2004 [cited by applicant]
US 20050118623A1 · Belousov et al. · 2005 [cited by applicant]
US 20050130923A1 · Bhat et al. · 2005 [cited by applicant]
US 20060074035A1 · Hong et al. · 2006 [cited by applicant]
US 20070287831A1 · Seth et al. · 2007 [cited by applicant]
US 20080039618A1 · Allerson et al. · 2008 [cited by applicant]
US 20080300163A1 · Cho et al. · 2008 [cited by applicant]
US 20090155844A1 · Yokoyama et al. · 2009 [cited by applicant]
US 20120077252A1 · Picataggio et al. · 2012 [cited by applicant]
US 20120244112A1 · Ast et al. · 2012 [cited by applicant]
US 20140314864A1 · Cheng et al. · 2014 [cited by applicant]
US 20140328791A1 · Bossard et al. · 2014 [cited by applicant]
US 20170369871A1 · Ptacin et al. · 2017 [cited by applicant]
US 20190218257A1 · Romesberg et al. · 2019 [cited by applicant]
US 20190376054A1 · Ptacin et al. · 2019 [cited by applicant]
US 20200017540A1 · Romesberg et al. · 2020 [cited by applicant]
US 20200024597A1 · Ptacin et al. · 2020 [cited by applicant]
US 20200131555A1 · Ptacin et al. · 2020 [cited by applicant]
US 20200224234A1 · Romesberg et al. · 2020 [cited by applicant]
US 20200277342A1 · Romesberg et al. · 2020 [cited by applicant]
US 20200318122A1 · Romesberg et al. · 2020 [cited by applicant]
US 20200377877A1 · Romesberg et al. · 2020 [cited by applicant]
US 20200392550A1 · Romesberg et al. · 2020 [cited by applicant]
US 20210222147A1 · Ptacin et al. · 2021 [cited by applicant]
US 20220228148A1 · Romesberg et al. · 2022 [cited by applicant]
US 20220243244A1 · Romesberg et al. · 2022 [cited by applicant]
EP 0614907A1 · 1994 [cited by applicant]
EP 0629633A2 · 1994 [cited by applicant]
EP 2130835A1 · 2009 [cited by applicant]
JP 2007510401A · 2007 [cited by applicant]
WO WO9213869A1 · 1992 [cited by applicant]
WO WO9422890A1 · 1994 [cited by applicant]
WO WO9735869A1 · 1997 [cited by applicant]
WO WO9831697A1 · 1998 [cited by applicant]
WO WO9914226A2 · 1999 [cited by applicant]
WO WO9962923A2 · 1999 [cited by applicant]
WO WO0023456A1 · 2000 [cited by applicant]
WO WO0105801A1 · 2001 [cited by applicant]
WO WO0132887A1 · 2001 [cited by applicant]
WO WO02062816A1 · 2002 [cited by applicant]
WO WO02070533A2 · 2002 [cited by applicant]
WO WO03055898A1 · 2003 [cited by applicant]
WO WO2004007713A1 · 2004 [cited by applicant]
WO WO2004106356A1 · 2004 [cited by applicant]
WO WO2005021570A1 · 2005 [cited by applicant]
WO WO2005026187A1 · 2005 [cited by applicant]
WO WO2005045015A2 · 2005 [cited by applicant]
WO WO2006049297A1 · 2006 [cited by applicant]
WO WO2007015557A1 · 2007 [cited by applicant]
WO WO2007066737A1 · 2007 [cited by applicant]
WO WO2007085485A2 · 2007 [cited by applicant]
WO WO2007093599A1 · 2007 [cited by applicant]
WO WO2007134181A2 · 2007 [cited by applicant]
WO WO2008067825A1 · 2008 [cited by applicant]
WO WO2008101157A1 · 2008 [cited by applicant]
WO WO2008150729A2 · 2008 [cited by applicant]
WO WO2008154401A2 · 2008 [cited by applicant]
WO WO2009006478A2 · 2009 [cited by applicant]
WO WO2009123216A1 · 2009 [cited by applicant]
WO WO2011043385A1 · 2011 [cited by applicant]
WO WO2011139699A2 · 2011 [cited by applicant]
WO WO2015021432A1 · 2015 [cited by applicant]
WO WO2016115168 · 2016 [cited by applicant]
WO WO2017106767A1 · 2017 [cited by applicant]
WO WO2017223528A1 · 2017 [cited by applicant]
WO WO2019014262A1 · 2019 [cited by applicant]
WO WO2019133883A1 · 2019 [cited by applicant]
WO WO2021067313A1 · 2021 [cited by applicant]
WO WO2022087475A1 · 2022 [cited by applicant]
Acsadi et al. Human Dystrophin Expression in mdx Mice After Intramuscular Injection of DNA Constructs. Nature 352:815-818 (1991). [cited by applicant]
Adhikary et al. Adaptive Mutations Alter Antibody Structure and Dynamics During Affinity Maturation. Biochemistry 54(11):2085-93 (2015). [cited by applicant]
Agris. Decoding the genome: a modified view. Nucleic Acids Res 32:223-238 (2004). [cited by applicant]
Ambrogelly et al. Pyrrolysine is not hardwired for cotranslational insertion at UAG condons. PNAS 104(9):3141-3146 (2007). [cited by applicant]
Amiri et al. Deep origin of plastid/parasite ATP/ADP translocases. J. Mol. Evol. 56:137-150 (2003). [cited by applicant]
Arenas-Ramirez et al. Improved cancer immunotherapy by a CD25-mimobody conferring selectivity to human interleukin-2. Sci Transl Med 8:367ra166 (Nov. 30, 2016). 13 pages. [cited by applicant]
Arie et al. Phylogenetic identification of n-alkane assimilating Candida yeasts based on nucleotide divergence in the 59 end of LSU rDNA gene. J Gen Appl Microbiol. 46(5):257-262 (2000). [cited by applicant]
Ast et al. Diatom plastids depend on nucleotide import from the cytosol. PNAS USA 106:3621-3626 (2009). [cited by applicant]
Beigelman et al. Synthesis of 5′-C-Methyl-D-allo- & L-Talo-ribonucleoside 3′-O-Phosphoramidites & Their Incorporation into Hammerhead Ribozymes. Nucleosides and Nucleotides 14(3-5):901-905 (1995). [cited by applicant]
Bentebibel et al. The Novel IL-2 Cytokine Immune Agonist NKTR-214 Harnesses the Adaptive and Innate Immune System for the Treatment of Solid Cancers. Poster #P77. Society for Immunotherapy of Cancer 2017 Annual Meeting … [cited by applicant]
Berger et al. Stability and selectivity of unnatural DNA with five-membered-ring nucleobase analogues. J Am Chem Soc 124(7):1222-6 (2002). [cited by applicant]
Berger et al. Stable and selective hybridization of oligonucleotides with unnatural hydrophobic bases. Angew Chem Int Ed Engl 39:2940-2942 (2000). [cited by applicant]
Berger et al. Universal bases for hybridization, replication and chain termination. Nucleic Acids Res 28(15):2911-2914 (2000). [cited by applicant]
Betz et al. KlenTaq polymerase replicates unnatural base pairs by inducing a Watson-Crick geometry. Nat Chem Biol 8:612-614 (2012). [cited by applicant]
Betz et al. Structural insights into DNA replication without hydrogen bonds. J Am Chem Soc 135:18637-18643 (2013). [cited by applicant]
Bhatt et al. Peripheral Blood Lymphocyte Responses in Patients with Renal Cell Carcinoma treated with High-Dose Interleukin-2. Poster (SITC 2018). [cited by applicant]
Biocentury Innovations publication Oct. 27, 2016 (26 pgs). [cited by applicant]
Bohringer et al. Synthesis of 5′-deoxy-5′-methylphosphonate linked thymidine oligonucleotides. Tet Lett 34:2723-2726 (1993). [cited by applicant]
Bordo et al. Suggestions for “safe” residue substitutions in site-directed mutagenesis. J Mol Biol 217:721-729 (1991). [cited by applicant]
Boyman et al. Selective Stimulation of T Cell subsets with Antibody-Cytokine Immune Complexes. Science 311:1924-1927 (2006). [cited by applicant]
Boyman et al. Selectively Expanding Subsets of T Cells in Mice by Injection of Interleukin-2/Antibody Complexes: Implications for Transplantation Tolerance. Transplantation Proceedings 44:1032-1034 (2012). [cited by applicant]
Boyman et al. The role of interleukin-2 during homeostatis and activation of the immune system. Nature 12:180-190 (2012). [cited by applicant]
Braasch et al. Locked nucleic acid (LNA): fine-tuning the recognition of DNA and RNA. Chem Bio 8:1-7 (2001). [cited by applicant]
Branca. Rekindling cancer vaccines. Nat Biotechnol 34(10):1019-1025 (2016). [cited by applicant]
Cann et al. A heterodimeric DNA polymerase: Evidence that members of Euryarchaeota possess a distinct DNA polymerase. PNAS USA 95:14250 (1998). [cited by applicant]
Cariello et al. Fidelity of Thermococcus litoralis DNA polymerase (VentTM) in PCR determined by denaturing gradient gel electrophoresis Nucl Acid Res 19:4193-4198 (1991). [cited by applicant]
Charych et al. Combining Complementary Mechanisms of Immune Activation: NKTR-214, a biased IL-2 Pathway Agonist and Immune Checkpoint Antagonists. Poster Abstract 3018. ESMO Annual Meeting (Oct. 9, 2016, Copenhagen, Den… [cited by applicant]
Chastgner et al. Lack of intermediate-affinity interleukin-2 receptor in mice leads to dependence on interkeukin-2 receptor α,β and γ chain expression for T cell growth. Eur J Immunol 26:201-206 (1996). [cited by applicant]
Chatterjee et al. A Versatile Platform for Single- and Multiple-Unnatural Amino Acid Mutagenesis in [cited by applicant]
Chaturvedi et al. Stabilization of triple-stranded oligonucleotide complexes: use of probes containing alternating phosphodiester and stereo-uniform cationic phosphoramidate linkages. Nucleic Acids Res. 24:2318-2323 (19… [cited by applicant]
Chen et al. A novel human IL-2 mutein with minimal systemic toxicity exerts greater antitumor efficacy than wild-type IL-2. Cell Death& Disease 9:989 (2018). [cited by applicant]
Chen et al. Directed polymerase evolution. FEBS Lett. 588(2):219-229 (2014). [cited by applicant]
Chen et al. Phosphonate Analogues of Cytosine Arabinoside Monophosphate. Phosphorus, Sulfur and Silicon 177:1783-1786 (2002). [cited by applicant]
Chen et al. The expanding world of DNA and RNA. Curr Opin Chem Biol 34:80-87 (2016). [cited by applicant]
Chien et al. Deoxyribonucleic acid polymerase from the extreme thermophile Thermus aquaticus. J Bacteriol 127:1550-1557 (1976). [cited by applicant]
Collingwood et al. The Synthesis and Incorporation in Oligonucleotides of a Thymidine Dimer Containing an Internucleoside Phosphinate Linkage. Synlett 7:703-705 (1995). [cited by applicant]
Crooke et al. Pharmacokinetic properties of several novel oligonucleotide analogs in mice. J Pharmacol Exp Ther 277:923-937 (1996). [cited by applicant]
Dahl et al. Discovery and validation of a series of aryl sulfonamides as selective inhibitors of tissue-nonspecific alkaline phosphatase (TNAP). J Med Chem 52(21):6919-6925 (2009). [cited by applicant]
De Mesmaeker et al. Amide-Modified Oligonucleotides with Preorganized Backbone and Furanose Rings: Highly Increased Thermodynamic Stability of the Duplexes Formed with their RNA and DNA Complements. Synlett 1997(11)1287… [cited by applicant]
Diab et al. NKTR-214 (CD-122-biased agonist) plus nivolumab in patients with advanced solid tumors: Preliminary phase 1/2 results of PIVOT. Powerpoint presentation. ClinicalTrials.gov NCT02983045. 2018 ASCO Annual Meeti… [cited by applicant]
Diab et al. Pivot-02: Preliminary safety, efficacy and biomarker results from dose escalation of the Phase 1/2 study of CD-122-biased agonist NKTR-214 plus nivolumab in patients with locally advanced/metastatic melanoma… [cited by applicant]
Diaz et al. Accuracy of replication in the polymerase chain reaction. Comparison between Thermotoga maritima DNA polymerase and Thermus aquaticus DNA polymerase. Braz J Med Res 31:1239-1242 (1998). [cited by applicant]
Dien et al. Eight-Letter DNA. Biochemistry 58:2581-2583 (2019). [cited by applicant]
Dien et al. Expansion of the genetic code via expansion of the genetic alphabet. Curr Opin Chem Biol 46:196-202 (2018). [cited by applicant]
Dien et al. Progress Toward a Semi-Synthetic Organism with an Unrestricted Expanded Genetic Alphabet. J Am Chem Soc. 140:16115-16123 (2018). [cited by applicant]
Dranoff. Cytokines in cancer pathogenesis and cancer therapy. Nature Reviews Cancer 4:11-22 (2004). [cited by applicant]
Dupradeau et al. Differential solvation and tautomer stability of a model base pair within the minor and major grooves of DNA. J Am Chem Soc 127(44):15612-7 (2005). [cited by applicant]
Egholm et al. PNA hybridizes to complementary oligonucleotides obeying the Watson-Crick hydrogen-bonding rules. Nature 365(6446):566-568 (1993). [cited by applicant]
El Yacoubi et al. Biosynthesis and function of posttranscriptional modifications of transfer RNAs. Annu Rev Genet 46:69-95 (2012). [cited by applicant]
Elayadi et al. Application of PNA and LNA oligomers to chemotherapy. Curr Opinion Invens Drugs 2:558-561 (2001). [cited by applicant]
Ellington et al. In vitro selection of RNA molecules that bind specific ligands. Nature 346:818-822 (1990). [cited by applicant]
Englisch et al. Chemically Modified Oligonucleotides as Probes and Inhibitors. Angew. Chem. Int. Ed. Eng. 30:613-629 (1991). [cited by applicant]
Eppacher et al. Synthesis and Incorporation of C(5′)-Ethynylated Uracil-Derived Phosphoramidites into RNA. Helvetica Chimica Acta 87:3004-3020 (2004). [cited by applicant]
Fa et al. Expanding the substrate repertoire of a DNA polymerase by directed evolution. J Am Chem Soc 126(6):1748-54 (2004). [cited by applicant]
Fairhurst et al. Synthesis and Hybridisation Properties of Phosphonamidate Ester Modified Nucleic Acid. Synlett 4:467-472 (2001). [cited by applicant]
Fan et al. Rationally evolving tRNAPyl for efficient incorporation of noncanonical amino acids. Nucleic Acids Res 43(22):e156 (2015). [cited by applicant]
Feldman et al. A Tool for the Import of Natural and Unnatural Nucleoside Triphosphates into Bacteria. J Am Chem Soc 140(4):1447-1454 (2018). [cited by applicant]
Feldman et al. Chemical Stabilization of Unnatural Nucleotide Triphosphates for the in Vivo Expansion of the Genetic Alphabet. J Am Chem Soc 139(6):2464-2467 (2017). [cited by applicant]
Feldman et al. In Vivo Structure-Activity Relationships and Optimization of an Unnatural Base Pair for Replication in a Semi-Synthetic Organism. J Am Chem Soc 139:11427-11433 (2017). [cited by applicant]
Feldman et al. Optimization of Replication, Transcription, and Translation in a Semi-Synthetic Organism. J Am Chem Soc 141:10644-10653 (2019). [cited by applicant]
Feldman. Expansion of the Genetic Alphabet: A Chemist's Approach to Synthetic Biology. Acc Chem Res 51(2):394-403 (2018). [cited by applicant]
Fersht. Enzyme Structure and Mechanism, 2nd ed., W. H. Freeman & Co., New York (pp. 350-351) (1985). [cited by applicant]
Fidanza et al. Functionalization of oligonucleotides by the incorporation of thio-specific reporter groups. In Protocols for Oligonucleotide Conjugates. Protocols for Oligonucleotide Conjugates: Synthesis and Analytical… [cited by applicant]
Fidanza et al. Site-specific labeling of DNA sequences containing phosphorothioate diesters. JACS 114(14):5509-5517 (2002). [cited by applicant]
Floros et al. Anticancer Cytokines: Biology and Clinical Effects of Interferon-α2, Interleukin (IL)-2, IL-15, IL-21, and IL-12. Semin Oncol 42(4):539-548 (2015). [cited by applicant]
Fourrey et al. Photo Rearrangement of Phenyl Selenide Derivatives Access to Selenium Substituted C Nucleosides. Tetrahedron Letters 21:455-458 (1980). [cited by applicant]
Fourrey et al. S-Nucleoside photorearrangement. Access to pyridine pseudonucleosides. J. Org. Chem. 44(11):1902-1894 (1979). [cited by applicant]
Gallier et al. Ex-Chiral-Pool Synthesis of β-Hydroxyphosphonate Nucleoside Analogues. Eur J Org Chem 6:925-933 (2007). [cited by applicant]
Gardner et al. Comparative Kinetics of Nucleotide Analog Incorporation by Vent DNA Polymerase. J Biol Chem 279(12):11834-11842 (2004). [cited by applicant]
Gardner et al. Determinants of nucleotide sugar recognition in an archaeon DNA polymerase. Nucleic Acids Research 27(12):2545-2553 (1999). [cited by applicant]
Geze et al. Synthesis of sinefungin and its C-6′ epimer. J Am Chem Soc 105(26):7638-7640 (1983). [cited by applicant]
Gillies et al. A Low-Toxicity IL-2-based Immunocytokine Retains Antitumor Activity Despite Its High Degree of IL-2 receptor Selectivity. Clin Cancer Res 17(11):3673-3686 (2011). [cited by applicant]
Goldberg et al. Re: Z. Ram et al. In situ retroviral-mediated gene transfer for the treatment of brain tumors in rats. Cancer Res. 53:83-88 (1993). [cited by applicant]
Haferkamp et al. Functional expression and characterisation of membrane transport proteins. Plant Biol. 14:675-690 (2012). [cited by applicant]
Haferkamp et al. Tapping the nucleotide pool of the host: novel nucleotide carrier proteins of Protochlamydia amoebophila. Mol. Microbiol. 60:1534-1545 (2006). [cited by applicant]
Hampton et al. Design of substrate-site-directed inhibitors of adenylate kinase and hexokinase. Effect of substrate substituents on affinity on affinity for the adenine nucleotide sites. J Med Chem 19:1371-1377 (1976). [cited by applicant]
Hampton et al. Design of substrate-site-directed irreversible inhibitors of adenosine 5′-phosphate aminohydrolase. Effect of substrate substituents on affinity for the substrate site. J Med Chem 19(8):1029-1033 (1976). [cited by applicant]
Hampton et al. Synthesis of 6′-cyano-6′-deoxyhomoadenosine-6′-phosphonic acid and its phosphoryl and pyrophosphoryl anhydrides and studies of their interactions with adenine nucleotide utilizing enzymes. J Am Chem Soc 9… [cited by applicant]
Hancock et al. Expanding the Genetic Code of Yeast for Incorporation of Diverse Unnatural Amino Acids via a Pyrrolysyl-tRNA Synthetase/tRNA Pair. JACS 132:14819-14824 (2010). [cited by applicant]
Hari et al. Optimization of the pyridyl nucleobase scaffold for polymerase recognition and unnatural base pair replication. Chembiochem 9(17):2796-2799 (2008). [cited by applicant]
Hatch et al. Adenine nucleotide and lysine transport in Chlamydia psittaci. J. Bacteriol. 150:662-670 (1982). [cited by applicant]
Hayes et al. Combining computational and experimental screening for rapid optimization of protein properties. PNAS USA 99:15926-15931 (2002). [cited by applicant]
Heaton et al. Characterization of lymphokine-activated killing by human peripheral blood mononuclear cells stimulated with interleukin 2 (IL-2) analogs specific for the intermediate affinity IL-2 receptor. Cell Immunol … [cited by applicant]
Heaton et al. Human interleukin 2 analogues that preferentially bind the intermediate-affinity interleukin 2 receptor lead to reduced secondary cytokine secretion: implications for the use of these interleukin 2 analogu… [cited by applicant]
Henry et al. Beyond A, C, G and T: augmenting nature's alphabet. Curr Opin Chem Biol 7(6):727-33 (2003). [cited by applicant]
Henry et al. Determinants of unnatural nucleobase stability and polymerase recognition. J Am Chem Soc 125(32):9638-9646 (2003). [cited by applicant]
Henry et al. Efforts to expand the genetic alphabet: identification of a replicable unnatural DNA self-pair. J Am Chem Soc 126(22):6923-31 (2004). [cited by applicant]
Hinnisdaels et al. Direct cloning of PCR products amplified with Pwo DNA polymerase. Biotechniques 20:186-188 (1996). [cited by applicant]
Hirao et al., Unnatural base pair systems toward the expansion of the genetic alphabet in the central dogma. Proceedings of the Japan Academy, Series B, Phys Biol Sci. 88:345-367 (2012). [cited by applicant]
Horn et al. Bacterial endosymbionts of free-living amoebae. J. Eukaryot. Microbiol. 5:509-514 (2004). [cited by applicant]
Hu et al. The Generation of Low Toxicity Interleukin-2 Fusion Proteins Devoid of Vasopermeability Activity. Blood 101(12):4853-61 (2003). [cited by applicant]
Hurwitz et al. A Novel Immune Agonist, NKTR-214, Increases the Number of Activity of CD8+ Tumor Infiltrating Lymphocytes in Patients with Advance Renal Cell Carcinoma. Poster Abstract #454. Poster Session C. ASCO Feb. 1… [cited by applicant]
Hutter et al. From Phosphate to Bis(methylene) Sulfone: Non-Ionic Backbone Linkers in DNA. Helvetica Chimica Acta 85:2777-2806 (2002). [cited by applicant]
Hwang et al. Polymerase recognition and stability of fluoro-substituted pyridone nucleobase analogues. Chembiochem 8:1606-1611 (2007). [cited by applicant]
Hwang et al. Substituent effects on the pairing and polymerase recognition of simple unnatural base pairs. Nucleic Acids Res 34(7):2037-45 (2006). [cited by applicant]
Hwang et al. The effects of unnatural base pairs and mispairs on DNA duplex stability and solvation. Nucleic Acids Res 37(14):4757-4763 (2009). [cited by applicant]
Hwang et al. Unnatural substrate repertoire of A, B, and X family DNA polymerases. J Am Chem Soc 130(44):14872-14882 (2008). [cited by applicant]
Insight-Esprit Study Group et al. Interleukin-2 Therapy in Patients with HIV Infection. N Engl J Med. 361(16):1548-59 (2009). [cited by applicant]
Ishizuka et al. Site-specific functionalization of RNA molecules by an unnatural base pair transcription system via click chemistry. Chem. Comm. 48:10835-10837 (2012). [cited by applicant]
Jager et al. Oligonucleotide N-alkylphosphoramidates: synthesis and binding to polynucleotides. Biochemistry 27:7247-7246 (1988). [cited by applicant]
Jones et al. A Subset of Latency-Reversing Agents Expose HIV-Infected Resting CD4+ T-Cells to Recognition by Cytotoxic T-Lymphocytes. PLoS Pathogens 12(4):e1005545 (2016). [cited by applicant]
Juncosa-Ginesta et al. Improved efficiency in site-directed mutagenesis by PCR using a [cited by applicant]
Jung et al. Synthesis of phosphonate derivatives of uridine, cytidine, and cytosine arabinoside. Bioorg Med Chem 8:2501-2509 (2000). [cited by applicant]
Kabanov et al. A new class of antivirals: antisense oligonucleotides combined with a hydrophobic substituent effectively inhibit influenza virus reproduction and synthesis of virus-specific proteins in MDCK cells. FEBS … [cited by applicant]
Kandimalla et al. Effect of chemical modifications of cytosine and guanine in a CpG-motif of oligonucleotides: structure-immunostimulatory activity relationships. Bioorg. Med. Chem. 9:807-813 (2001). [cited by applicant]
Kappler et al. Isozyme-specific enzyme inhibitors. 11. L-homocysteine-ATP S-C5′ covalent adducts as inhibitors of rat methionine adenosyltransferases. J Med Chem 29:1030-1038 (1986). [cited by applicant]
Kappler et al. Species- or isozyme-specific enzyme inhibitors. 8. Synthesis of disubstituted two-substrate condensation products as inhibitors of rat adenylate kinases. J Med Chem 25:1179-1184 (1982). [cited by applicant]
Kaur et al. Thermodynamic, Counterion, and Hydration Effects for the Incorporation of Locked Nucleic Acid Nucleotides into DNA Duplexes. Biochemistry 45(23):7347-7344 (2006). [cited by applicant]
Khalili et al. Mechanistic modeling of a new kinetically-controlled CD122 agonist for cancer immunotherapy: NKTR-214 pharmacokinetics, pharmacodynamics, and receptor pharmacology. Poster Abstract 1614. AACR Annual Meeti… [cited by applicant]
Kim et al. Stability and polymerase recognition of pyridine nucleobase analogues: role of minor-groove H-bond acceptors. Angew Chem Int Ed Engl 45(46):7809-12 (2006). [cited by applicant]
Kimoto et al. Generation of high-affinity DNA aptamers using an expanded genetic alphabet. Nat. Biotech. 31(5):453-458 (2013). [cited by applicant]
Kivimäe et al. Comprehensive Antitumor Immune Activation by a Novel TLR 7/8 Targeting Agent NKTR-262 Combined With CD122-Biased Immunostimulary Cytokine NKTR-214. Poster #3755 (AACR Apr. 14-18, 2018). [cited by applicant]
Kivimäe et al. Harnessing the innate and adaptive immune system to eradicate treated and distant untreated solid tumors. Poster #P275. Immunotherapy of Cancer 2017 Annual Meeting (2017). [cited by applicant]
Klein et al. Cergutuzumab amunaleukin (CEA-IL2v), a CEA-targeted IL-2 variant-based immunocytokine for combination cancer immunotherapy: Overcoming limitations of aldesleukin and conventional IL-2-based immunocytokines.… [cited by applicant]
Koshkin et al. LNA (locked nucleic acids): synthesis of the adenine, cytosine, guanine 5-methylcytosine, thymine and uracil bicyclonucleoside monomers, oligomerisation, and unprecedented nucleic acid recognition. Tetrah… [cited by applicant]
Kranaster et al. Increased single-nucleotide discrimination in allele-specific polymerase chain reactions through primer probes bearing nucleobase and 2′-deoxyribose modifications. Chem Eur J 13(21):6115-6122 (2007). [cited by applicant]
Krieg et al. Improved IL-2 immunotherapy by selective stimulation of IL-2 receptors on lymphocytes and endothelial cells. PNAS USA 107(26):11906-11911 (Jun. 29, 2010). [cited by applicant]
Kroschwitz. The Concise Encyclopedia of Polymer Science and Engineering. (pp. 858-859) (1990). [cited by applicant]
Kubelka et al. Synthesis of 2,6-disubstituted pyridin-3-y1 C-2′-deoxyribonucleosides through chemoselective transformations of bromo-chloropyridine C-nucleosides. Org. Biomol. Chem. 11:4702-4718 (2013). [cited by applicant]
Kumar et al. The First Analogues of LNA (Locked Nucleic Acids): Phosphorothioate LNA and 2′-Thio-LNA. Bioorg Med Chem Lett 8:2219-2222 (1998). [cited by applicant]
Langowski et al. The CD122-biased immunostimulatory cytokine NKTR-214 combined with checkpoint blockade leads to mobilization of anti-tumor immunity and synergistic activity. Poster Abstract 311. 2016 CR-CIMT-EATIR-AACR… [cited by applicant]
Lavergne et al. Expanding the scope of replicable unnatural DNA: Stepwise optimization of a predominantly hydrophobic base pair. JACS 135:5408-5419 (2013). [cited by applicant]
Lavergne et al. FRET Characterization of Complex Conformational Changes in a Large 16S Ribosomal RNA Fragment Site-Specifically Labeled Using Unnatural Base Pairs. ACS Chem Biol 11(5):1347-53 (2016). [cited by applicant]
Lavergne et al. Major groove substituents and polymerase recognition of a class of predominantly hydrophobic unnatural base pairs. Chem. Eur. J. 18:1231-1239 (2012). [cited by applicant]
Lazear et al. Targeting of IL-2 to cytotoxic lymphocytes as an improved method of cytokine-driven immunotherapy. Oncoimmunology 6(2):e1265721 (2017). [cited by applicant]
Lecomte et al. Selective Inactivation of the 3′ to 5′ exonuclease activity of [cited by applicant]
Leconte et al. Amplify this! DNA and RNA get a third base pair. Nat Meth 3:667-668 (2006). [cited by applicant]
Leconte et al. An efficiently extended class of unnatural base pairs. J Am Chem Soc 128(21):6780-1 (2006). [cited by applicant]
Leconte et al. Chemical biology: a broader take on DNA. Nature 444:553-555 (2006). [cited by applicant]
Leconte et al. Directed Evolution of DNA Polymerases for Next-Generation Sequencing. Angew Chem Int Ed Engl 49(34):5921-5924 (2010). [cited by applicant]
Leconte et al. Discovery, characterization, and optimization of an unnatural base pair for expansion of the genetic alphabet. J Am Chem Soc 130(7):2336-2343 (2008). [cited by applicant]
Leconte et al. Efforts towards expansion of the genetic alphabet: pyridone and methyl pyridone nucleobases. Angew Chem Int Ed Engl 45(26):4326-9 (2006). [cited by applicant]
Leconte et al. Polymerase evolution: efforts toward expansion of the genetic code. J Am Chem Soc 127(36):12470-1 (2005). [cited by applicant]
Ledbetter et al. Editorial overview: Expanding the genetic alphabet and code. Curr Opin Chem Biol 46:A1-A2 (2018). [cited by applicant]
Ledbetter et al. Reprograming the Replisome of a Semisynthetic Organism for the Expansion of the Genetic Alphabet. J Am Chem Soc. 140:758-765 (2018). [cited by applicant]
Ledbetter et al. Site-Specific Labeling of DNA via PCR with an Expanded Genetic Alphabet. Methods Mol Biol 1973:193-212 (2019). [cited by applicant]
Letourneau et al. IL-2/anti-IL-2 antibody complexes show strong biological activity by avoiding interaction with IL-2 receptor alpha subunit CD25. PNAS USA 107:2171-2176 (2010). [cited by applicant]
Letsinger et al. Cholesteryl-conjugated oligonucleotides: Synthesis, properties, and activity as inhibitors of replication of human immunodeficiency virus in cell culture. PNAS 86:6553-6556 (1989). [cited by applicant]
Levin. It's prime time for reverse transcriptase. Cell 88:5-8 (1997). [cited by applicant]
Li et al. Improved Inhibition of Tumor Growth by Diabody-Drug Conjugates via Half-Life Extension. Bioconjugate Chem 30:1232-1243 (2019). [cited by applicant]
Li et al. Natural-like Replication of an Unnatural Base Pair for the Expansion of the Genetic Alphabet and Biotechnology Applications. J Am Chem Soc 136:826-829 (2014). [cited by applicant]
Li et al. Site-Specifically Arraying Small Molecules or Proteins on DNA Using an Expanded Genetic Alphabet. Chem Eur J 19:14205-14209 (2013). [cited by applicant]
Liu et al. Adding new chemistries to the genetic code. Annu Rev Biochem 79:413-444 (2010). [cited by applicant]
Lopes et al. Characterization of the Pharmacodynamic Immune Response to a Novel Immunotherapeutic Agent, ALKS 4230, in Mice and Non-Human Primates. Poster 22 (Abstract #2663) (AACR 2017). [cited by applicant]
Lopes et al. Ex Vivo Expansion and Activation of Human Lymphocytes With a Selective Activator of Effector Cells. Abstract #3158 Poster (AACR 2015). [cited by applicant]
Losey et al. Abstract #4280: Utilizing a Selective Agonist of the Intermediate-Affinity IL-2 Receptor With an Improved Pharmacokinetic Profile Leads to an Enhanced Immunostimulatory Response With Reduced Toxicity in Mic… [cited by applicant]
Losey et al. Efficacy of ALKS 4230, a Novel Immunotherapeutic Agent, in Murine Syngeneic Tumor Models Alone and in Combination with Immune checkpoint Inhibitors. Poster 25 (Abstract #591) (AACR 2017). [cited by applicant]
Losey et al. Utilizing a Selective Agonist of the Intermediate-Affinity IL-2 Receptor With an Improved Pharmacokinetic Profile Leads to an Enhanced Immunostimulatory Response With Reduced Toxicity in Mice. Poster for Ab… [cited by applicant]
Lou et al. Fixing vascular leak in IL-2 immunotherapy. SciBX 3(27):2 pgs (2010). [cited by applicant]
Ludwig et al. Rapid and efficient synthesis of nucleoside 5′-0-(1-thiotriphosphates), 5′-triphosphates and 2′,3′-cyclophosphorothioates using 2-chloro-4H-1,3,2-benzodioxaphosphorin-4-one. J. Org. Chem. 54:631-635 (1989). [cited by applicant]
Lundberg et al. High-fidelity amplification using a thermostable DNA polymerase isolated from Pyrococcus furiosus. Gene 108:1-6 (1991). [cited by applicant]
Malyshev et al. A semi-synthetic organism with an expanded genetic alphabet. Nature 509(7500):385-388 (2014). [cited by applicant]
Malyshev et al. Efficient and sequence-independent replication of DNA containing a third base pair establishes a functional six-letter genetic alphabet. PNAS USA 109:12005-12010 (2012). [cited by applicant]
Malyshev et al. PCR with an Expanded Genetic Alphabet. JACS 131(41):14620-14621 (2009). [cited by applicant]
Malyshev et al. Solution structure, mechanism of replication, and optimization of an unnatural base pair. Chem Eur J 16:12650-12659 (2010). [cited by applicant]
Manoharan et al. Chemical Modifications to Improve Uptake and Bioavailability of Antisense Oligonucleotides. Ann. N.Y. Acad. Scie 660:306-309 (1992). [cited by applicant]
Manoharan et al. Cholic Acid-Oligonucleotide Conjugates for Antisense Applications. Bioorg. Med. Chem. Let 4:1053-1060 (1994). [cited by applicant]