IP Library › Granted Patent US 12,391,689
Granted Patent B2
US 12,391,689 · App. 17/689,741 · Granted Aug 19, 2025

Synthesis of key intermediate of KRAS G12C inhibitor compound

Inventors: Andrew Thomas Parsons (Cambridge, MA); Brian McNeil Cochran (San Diego, CA); William Powazinik, IV (Thousand Oaks, CA); Marc Anthony Caporini (Belmont, MA)
Assignee: AMGEN INC.
C07D471/04C07C69/76C07C309/24
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 12,391,689
App. No.
17/689,741
Granted
Aug 19, 2025
Kind
B2
Abstract

The present invention relates to an improved, efficient, scalable process to prepare intermediate compounds, such as compound 5M, having the structure useful for the synthesis of compounds that target KRAS G12C mutations, such as

Claims (14)

1. A composition, the composition comprising a compound of Formula 4:

and a compound of Formula B:

2. The composition of claim 1 , wherein the compound of Formula 4 is:

3. The composition of claim 1 , wherein the compound of Formula 4 is:

4. The composition of claim 1 , wherein the compound of Formula B is:

5. The composition of claim 1 , wherein the compound of Formula B is:

6. The composition of claim 1 , wherein the composition comprises a 2 to 1 ratio of the compound of Formula 4 to the compound of Formula B.

7. The composition of claim 1 , wherein the composition further comprises 2-methyltetrahydrofuran having the formula:

8. The composition of claim 7 , wherein the ratio of the 2-methyltetrahydrofuran to the compound of formula B is 2 to 1.

9. The composition of claim 7 , wherein the composition comprises:

10. The composition of claim 9 , wherein the composition comprises:

11. The composition of claim 9 , wherein the composition comprises:

12. The composition of claim 9 , wherein the composition comprises:

13. The composition of claim 9 , wherein the composition comprises:

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 21, 2022
From: PARSONS, ANDREW THOMAS; COCHRAN, BRIAN MCNEIL; POWAZINIK, WILLIAM, IV; CAPORINI, MARC ANTHONY
To: AMGEN INC.
Reel/Frame 061503/0368 →
Continuity (3)
Continuation 16685841 · Nov 15, 2019
Provisional Application 62768802 · Nov 16, 2018
Related Publication 20220220112A1 · Jul 14, 2022
References Cited (400)
US 4232027A · Turk et al. · 1980 [cited by applicant]
US 5100883A · Schiehser · 1992 [cited by applicant]
US 5118677A · Caufield · 1992 [cited by applicant]
US 5118678A · Kao et al. · 1992 [cited by applicant]
US 5120842A · Failli et al. · 1992 [cited by applicant]
US 5151413A · Caufield et al. · 1992 [cited by applicant]
US 5256790A · Nelson · 1993 [cited by applicant]
US 5258389A · Goulet et al. · 1993 [cited by applicant]
US 5521184A · Zimmerman · 1996 [cited by applicant]
US 5650415A · Tang et al. · 1997 [cited by applicant]
US 5656643A · Spada et al. · 1997 [cited by applicant]
US 5712291A · D'Amato · 1998 [cited by applicant]
US 5728813A · Lyman et al. · 1998 [cited by applicant]
US 5747498A · Schnur et al. · 1998 [cited by applicant]
US 5770599A · Gibson · 1998 [cited by applicant]
US 5789427A · Chen et al. · 1998 [cited by applicant]
US 5792783A · Tang et al. · 1998 [cited by applicant]
US 5861510A · Piscopio et al. · 1999 [cited by applicant]
US 5863949A · Robinson et al. · 1999 [cited by applicant]
US 5892112A · Levy et al. · 1999 [cited by applicant]
US 5969110A · Beckmann et al. · 1999 [cited by applicant]
US 5981245A · Fox et al. · 1999 [cited by applicant]
US 5990141A · Hirth et al. · 1999 [cited by applicant]
US 6057124A · Bartley et al. · 2000 [cited by applicant]
US 6111090A · Gorman et al. · 2000 [cited by applicant]
US 6232447B1 · Cerretti · 2001 [cited by applicant]
US 6235764B1 · Larson et al. · 2001 [cited by applicant]
US 6258812B1 · Bold et al. · 2001 [cited by applicant]
US 6413932B1 · Cerretti et al. · 2002 [cited by applicant]
US 6515004B1 · Misra et al. · 2003 [cited by applicant]
US 6596852B2 · Cerretti et al. · 2003 [cited by applicant]
US 6630500B2 · Gingrich et al. · 2003 [cited by applicant]
US 6656963B2 · Firestone et al. · 2003 [cited by applicant]
US 6713485B2 · Carter et al. · 2004 [cited by applicant]
US 6727225B2 · Wiley · 2004 [cited by applicant]
US 7025962B1 · Gorman et al. · 2006 [cited by applicant]
US 7358384B2 · Morii et al. · 2008 [cited by applicant]
US 7361760B2 · Sircar et al. · 2008 [cited by applicant]
US 7618632B2 · Collins et al. · 2009 [cited by applicant]
US 7812135B2 · Smith et al. · 2010 [cited by applicant]
US 7838700B2 · Martin et al. · 2010 [cited by applicant]
US 8388967B2 · Smith et al. · 2013 [cited by applicant]
US 8586023B2 · Shiku et al. · 2013 [cited by applicant]
US 8591886B2 · Ponath et al. · 2013 [cited by applicant]
US 10519146B2 · Lanman et al. · 2019 [cited by applicant]
US 10532042B2 · Lanman et al. · 2020 [cited by applicant]
US 10640504B2 · Lanman et al. · 2020 [cited by applicant]
US 10988485B2 · Minatti et al. · 2021 [cited by applicant]
US 11045484B2 · Wurz et al. · 2021 [cited by applicant]
US 11053226B2 · Shin et al. · 2021 [cited by applicant]
US 11090304B2 · Allen et al. · 2021 [cited by applicant]
US 11096939B2 · Booker et al. · 2021 [cited by applicant]
US 11299491B2 · Parsons · 2022 [cited by examiner]
US 11905281B2 · Lanman et al. · 2024 [cited by applicant]
US 20020042368A1 · Fanslow, III et al. · 2002 [cited by applicant]
US 20030105091A1 · Riedl et al. · 2003 [cited by applicant]
US 20030162712A1 · Cerretti et al. · 2003 [cited by applicant]
US 20090012085A1 · Baum et al. · 2009 [cited by applicant]
US 20140288045A1 · Ren et al. · 2014 [cited by applicant]
US 20150239900A1 · Li et al. · 2015 [cited by applicant]
US 20160159738A1 · Ren et al. · 2016 [cited by applicant]
US 20160166571A1 · Janes et al. · 2016 [cited by applicant]
US 20160297774A1 · Li et al. · 2016 [cited by applicant]
US 20180015087A1 · Liu et al. · 2018 [cited by applicant]
US 20180072723A1 · Blake et al. · 2018 [cited by applicant]
US 20180334454A1 · Lanman et al. · 2018 [cited by applicant]
US 20190077801A1 · Lanman et al. · 2019 [cited by applicant]
US 20190336514A1 · Wurz et al. · 2019 [cited by applicant]
US 20190343838A1 · Allen et al. · 2019 [cited by applicant]
US 20190345169A1 · Minatti et al. · 2019 [cited by applicant]
US 20190374542A1 · Allen et al. · 2019 [cited by applicant]
US 20190375749A1 · Chen et al. · 2019 [cited by applicant]
US 20200030324A1 · Booker et al. · 2020 [cited by applicant]
US 20200055845A1 · Lanman et al. · 2020 [cited by applicant]
US 20200069657A1 · Lanman et al. · 2020 [cited by applicant]
US 20200165231A1 · Shin et al. · 2020 [cited by applicant]
US 20200207766A1 · Lanman et al. · 2020 [cited by applicant]
US 20200222407A1 · Lipford et al. · 2020 [cited by applicant]
US 20200360374A1 · Henary et al. · 2020 [cited by applicant]
US 20200369662A1 · Chaves et al. · 2020 [cited by applicant]
US 20210009577A1 · Lanman et al. · 2021 [cited by applicant]
CN 101239913 · 2008 [cited by applicant]
DE 19629652A1 · 1998 [cited by applicant]
EP 0090505A2 · 1983 [cited by applicant]
EP 0520722A1 · 1992 [cited by applicant]
EP 0566226A1 · 1993 [cited by applicant]
EP 0606046A1 · 1994 [cited by applicant]
EP 0682027A1 · 1995 [cited by applicant]
EP 0407122A1 · 1996 [cited by applicant]
EP 0770622A2 · 1997 [cited by applicant]
EP 0780386A1 · 1997 [cited by applicant]
EP 0787772A2 · 1997 [cited by applicant]
EP 0818442A2 · 1998 [cited by applicant]
EP 0837063A1 · 1998 [cited by applicant]
EP 0931788A2 · 1999 [cited by applicant]
EP 0970070B1 · 2000 [cited by applicant]
EP 1004578A2 · 2000 [cited by applicant]
EP 1181017B1 · 2002 [cited by applicant]
EP 1786785B9 · 2007 [cited by applicant]
EP 1866339B1 · 2007 [cited by applicant]
EP 1947183A1 · 2008 [cited by applicant]
EP 1446372B1 · 2009 [cited by applicant]
EP 3401314A1 · 2019 [cited by applicant]
EP 3055290B1 · 2019 [cited by applicant]
JP 02233610A · 1990 [cited by applicant]
JP 2019031476A · 2019 [cited by applicant]
WO 1990005719A1 · 1990 [cited by applicant]
WO 1992005179A1 · 1992 [cited by applicant]
WO 1992020642A1 · 1992 [cited by applicant]
WO 1993011130A1 · 1993 [cited by applicant]
WO 1994002136A1 · 1994 [cited by applicant]
WO 1994002485A1 · 1994 [cited by applicant]
WO 1994009010A1 · 1994 [cited by applicant]
WO 1995009847A1 · 1995 [cited by applicant]
WO 1995014023A1 · 1995 [cited by applicant]
WO 1995016691A1 · 1995 [cited by applicant]
WO 1995019774A1 · 1995 [cited by applicant]
WO 1995019970A1 · 1995 [cited by applicant]
WO 1996027583A1 · 1996 [cited by applicant]
WO 1996030347A1 · 1996 [cited by applicant]
WO 1996031510A1 · 1996 [cited by applicant]
WO 1996033172A1 · 1996 [cited by applicant]
WO 1996033980A1 · 1996 [cited by applicant]
WO 1996041807A1 · 1996 [cited by applicant]
WO 1997002266A1 · 1997 [cited by applicant]
WO 1997013771A1 · 1997 [cited by applicant]
WO 1997019065A1 · 1997 [cited by applicant]
WO 1997027199A1 · 1997 [cited by applicant]
WO 1997030034A1 · 1997 [cited by applicant]
WO 1997030044A1 · 1997 [cited by applicant]
WO 1997032880A1 · 1997 [cited by applicant]
WO 1997032881A1 · 1997 [cited by applicant]
WO 1997034895A1 · 1997 [cited by applicant]
WO 1997038983A1 · 1997 [cited by applicant]
WO 1997038994A1 · 1997 [cited by applicant]
WO 1997049688A1 · 1997 [cited by applicant]
WO 1998002434A1 · 1998 [cited by applicant]
WO 1998002437A1 · 1998 [cited by applicant]
WO 1998002438A1 · 1998 [cited by applicant]
WO 1998002441A2 · 1998 [cited by applicant]
WO 1998003516A1 · 1998 [cited by applicant]
WO 1998007697A1 · 1998 [cited by applicant]
WO 1998007726A1 · 1998 [cited by applicant]
WO 1998014449A1 · 1998 [cited by applicant]
WO 1998014450A1 · 1998 [cited by applicant]
WO 1998014451A1 · 1998 [cited by applicant]
WO 1998017662A1 · 1998 [cited by applicant]
WO 1998030566A1 · 1998 [cited by applicant]
WO 1998033768A1 · 1998 [cited by applicant]
WO 1998033798A2 · 1998 [cited by applicant]
WO 1998034915A1 · 1998 [cited by applicant]
WO 1998034918A1 · 1998 [cited by applicant]
WO 1999007675A1 · 1999 [cited by applicant]
WO 1999007701A1 · 1999 [cited by applicant]
WO 1999020758A1 · 1999 [cited by applicant]
WO 1999029667A1 · 1999 [cited by applicant]
WO 1999035132A1 · 1999 [cited by applicant]
WO 1999035146A1 · 1999 [cited by applicant]
WO 1999040196A1 · 1999 [cited by applicant]
WO 1999045009A1 · 1999 [cited by applicant]
WO 1999052889A1 · 1999 [cited by applicant]
WO 1999052910A1 · 1999 [cited by applicant]
WO 1999061422A1 · 1999 [cited by applicant]
WO 2000002871A1 · 2000 [cited by applicant]
WO 2000012089A1 · 2000 [cited by applicant]
WO 2000059509A1 · 2000 [cited by applicant]
WO 2001003720A2 · 2001 [cited by applicant]
WO 2001014387A1 · 2001 [cited by applicant]
WO 2001032651A1 · 2001 [cited by applicant]
WO 2001037820A2 · 2001 [cited by applicant]
WO 2002055501A2 · 2002 [cited by applicant]
WO 2002059110A1 · 2002 [cited by applicant]
WO 2002066470A1 · 2002 [cited by applicant]
WO 2002068406A2 · 2002 [cited by applicant]
WO 2003042132A1 · 2003 [cited by applicant]
WO 2004005279A2 · 2004 [cited by applicant]
WO 2004007458A1 · 2004 [cited by applicant]
WO 2004007481A2 · 2004 [cited by applicant]
WO 2004009784A2 · 2004 [cited by applicant]
WO 2005005434A1 · 2005 [cited by applicant]
WO 2005007190A1 · 2005 [cited by applicant]
WO 2005011700A1 · 2005 [cited by applicant]
WO 2005016252A2 · 2005 [cited by applicant]
WO 2005021546A1 · 2005 [cited by applicant]
WO 2005055808A2 · 2005 [cited by applicant]
WO 2005115451A2 · 2005 [cited by applicant]
WO 2006044453A1 · 2006 [cited by applicant]
WO 2006083289A2 · 2006 [cited by applicant]
WO 2006121168A1 · 2006 [cited by applicant]
WO 2006122806A2 · 2006 [cited by applicant]
WO 2007133822A1 · 2007 [cited by applicant]
WO 2008070740A1 · 2008 [cited by applicant]
WO 2009036082A2 · 2009 [cited by applicant]
WO 2009055730A1 · 2009 [cited by applicant]
WO 2010003118A1 · 2010 [cited by applicant]
WO 2011028683A1 · 2011 [cited by applicant]
WO 2011051726A2 · 2011 [cited by applicant]
WO 2011090754A1 · 2011 [cited by applicant]
WO 2012142498A2 · 2012 [cited by applicant]
WO 2013039954A1 · 2013 [cited by applicant]
WO 2013155223A1 · 2013 [cited by applicant]
WO 2014143659A1 · 2014 [cited by applicant]
WO 2014152588A1 · 2014 [cited by applicant]
WO 2015001076A1 · 2015 [cited by applicant]
WO 2015054572A1 · 2015 [cited by applicant]
WO 2015075483A1 · 2015 [cited by applicant]
WO 2016044772A1 · 2016 [cited by applicant]
WO 2016049524A1 · 2016 [cited by applicant]
WO 2016049565A1 · 2016 [cited by applicant]
WO 2016049568A1 · 2016 [cited by applicant]
WO 2016164675A1 · 2016 [cited by applicant]
WO 2016168540A1 · 2016 [cited by applicant]
WO 2017015562A1 · 2017 [cited by applicant]
WO 2017058728A1 · 2017 [cited by applicant]
WO 2017058768A1 · 2017 [cited by applicant]
WO 2017058792A1 · 2017 [cited by applicant]
WO 2017058805A1 · 2017 [cited by applicant]
WO 2017058807A1 · 2017 [cited by applicant]
WO 2017058902A1 · 2017 [cited by applicant]
WO 2017058915A1 · 2017 [cited by applicant]
WO 2017087528A1 · 2017 [cited by applicant]
WO 2017100546A1 · 2017 [cited by applicant]
WO 2017172979A1 · 2017 [cited by applicant]
WO 2017201161A1 · 2017 [cited by applicant]
WO 2018064510A1 · 2018 [cited by applicant]
WO 2018068017A1 · 2018 [cited by applicant]
WO 2018119183A3 · 2018 [cited by applicant]
WO 2018140598A1 · 2018 [cited by applicant]
WO 2018217651A1 · 2018 [cited by applicant]
WO 2018218069A1 · 2018 [cited by applicant]
WO 2019051291A1 · 2019 [cited by applicant]
WO 2019213516A1 · 2019 [cited by applicant]
WO 2019213526A1 · 2019 [cited by applicant]
WO 2019217691A1 · 2019 [cited by applicant]
WO 2019232419A1 · 2019 [cited by applicant]
WO 2019241157A1 · 2019 [cited by applicant]
WO 2019243533A1 · 2019 [cited by applicant]
WO 2019243535A1 · 2019 [cited by applicant]
WO 2020050890A2 · 2020 [cited by applicant]
WO 2020102730A1 · 2020 [cited by applicant]
WO 2020106640A1 · 2020 [cited by applicant]
WO 2020232130A1 · 2020 [cited by applicant]
WO 2020236947A1 · 2020 [cited by applicant]
WO 2020236948A1 · 2020 [cited by applicant]
WO 2021081212A1 · 2021 [cited by applicant]
WO 2021097207A1 · 2021 [cited by applicant]
WO 2021097212A1 · 2021 [cited by applicant]
WO 2021126816A1 · 2021 [cited by applicant]
WO 2022076623A1 · 2022 [cited by applicant]
WO 2022109242A1 · 2022 [cited by applicant]
WO 2023172858A1 · 2023 [cited by applicant]
“A Phase 1, Study Evaluating the Safety, Tolerability, PK, and Efficacy of AMG 510 in Subjects With Solid Tumors With a S Mutation.” NCT03600883, comparison of version submitted Oct. 29, 2018 and Oct. 9, 2019 (update po… [cited by applicant]
“Acute Leukemia,” [cited by applicant]
“KRASG12C Inhibitor,” Mirati Therapeutics, retrieved on Nov. 27, 2018, from https://www.mirati.com/mrtx849/, 5 pages. [cited by applicant]
Ahmadian, et al., “Guanosine triphosphatase stimulation of oncogenic Ras mutants,” [cited by applicant]
Airoldi, et al., “Glucose-Derived Ras Pathway Inhibitors: Evidence of Ras-Ligand Binding and Ras-GEF (Cdc25) Interaction Inhibition,” [cited by applicant]
ATTC “Organism: [cited by applicant]
Barnett, et al., “Identification and characterization of pleckstrin-holomogy-domain-dependent and isoenzyme specific Akt inhibitors,” [cited by applicant]
Bhatia, et al., “A Review on Bioisosterism: A Rational Approach for Drug Design and Molecular Modification,” [cited by applicant]
Bull, et al., “Isoquino[2,1-c][1,3,2] Benzodiazaphosphorine Derivatives: New Potential Agents for Cancer Chemotherapy,” [cited by applicant]
Campillo, et al., “Novel Bronchodilators: Synthesis, Transamination Reactions, and Pharmacology of a Series of Pyrazino[2,3-c][1,2,6]thiadiazine 2,2-Dioxides,” [cited by applicant]
Canon, et al., “The clinical KRAS(G12C) inhibitor AMG 510 drives anti-tumour immunity,” [cited by applicant]
Cee, et al., “Discovery of AMG 510, a first-in-humancovalent inhibitor of KRAS [cited by applicant]
Cohen, “The development and therapeutic potential of protein kinase inhibitors,” [cited by applicant]
Cowen Slide deck—Warp Drive Bio, slides 1-32, “Corporate Overview Exploiting the Molecules and Mechanisms of Nature to Create Transformative Medicines” http://www.warpdrivebio.com/news/cowen%202016.pdf (last visited Apr… [cited by applicant]
Dasmahapatra, et al., “In vitro Combination Treatment with Perifosine and UCN-01 Demonstrates Synergism Against Prostate (PC-3) and Lung (A549) Epithelial Adenocarcinoma Cell Lines,” [cited by applicant]
Dermer, et al., “Another Anniversary for the War on Cancer,” [cited by applicant]
Douelle, et al., “Highly Diastereoselective Synthesis of vicinal Quaternary and Tertiary Stereocenters Using the Iodo-aldol Cyclization,” [cited by applicant]
Erkkilä, et al., “Mild Organocatalytic α-Methylenation of Aldehydes,” [cited by applicant]
Extended European Search Report for European Patent Application No. 19208193.2, dated Jun. 3, 2020, pp. 1-8. [cited by applicant]
Fakih, et al., “Phase 1 study evaluating the safety, tolerability, pharmacokinetics (PK), and efficacy of AMG 510, a novel small molecule KRASG12C inhibitor, in advanced solid tumors,” [cited by applicant]
Fakih, et al., “Phase 1 study evaluating the safety, tolerability, pharmacokinetics (PK), and efficacy of AMG 510, a novel small molecule KRASG12C inhibitor, in advanced solid tumors,” Presentation, ASCO, Chicago, IL, U… [cited by applicant]
Final Office Action for U.S. Appl. No. 15/984,855, mailed Mar. 28, 2019, 7 pages. [cited by applicant]
Final Office Action for U.S. Appl. No. 16/661,907, mailed Mar. 27, 2020, 29 pages. [cited by applicant]
Freshney, et al., Culture of Animal Cells, [cited by applicant]
Gentile, et al., “Discovery and Structural Investigation of Novel Binders to the Ras Switch II Pocket,” NCI Initiative Symposium Poster (2015). [cited by applicant]
Gills and Dennis, “The development of phosphatidylinositol ether lipid analogues as inhibitors of the serine/threonine kinase, Akt,” [cited by applicant]
Goldberg, et al., “Role of PD-1 and its ligand, B7-H1, in early fate decisions of CD8 T cells,” [cited by applicant]
Goldstein, et al., “Biological efficacy of a chimeric antibody to the epidermal growth factor receptor in a human tumor xenograft model,” [cited by applicant]
Golub, et al., “Molecular Classification of Cancer: Class Discovery and Class Prediction by Gene Expression Monitoring,” [cited by applicant]
Govindan, et al., “Safety, Efficacy, and Pharmacokinetics of AMG 510, a Novel KRASG12C Inhibitor, in Patients with Non-Small Cell Lung Cancer,” Abstract and Presentation, North American Conference on Lung Cancer (NACLC)… [cited by applicant]
Govindan, et al., “Phase 1 Study of AMG 510, a Novel KRAS G12C Inhibitor, in Advanced Solid Tumors with KRAS p.G12C Mutation,” Abstract, ESMO Congress, Barcelona, Spain, Sep. 27-Oct. 1, 2019. [cited by applicant]
Govindan, et al., “Phase 1 Study of AMG 510, a Novel KRAS G12C Inhibitor, in Advanced Solid Tumors with KRAS p.G12C Mutation,” Poster, ESMO Congress, Barcelona, Spain, Sep. 27, 2019-Oct. 1, 2019. [cited by applicant]
Govindan, et al., “Phase 1 Study of Safety, Tolerability, Pharmacokinetics, and Efficacy of AMG510, a Novel KRASG12C Inhibitor, in Non-Small Cell Lung Cancer,” Abstract and Presentation, World Conference on Lung Cancer … [cited by applicant]
Gura, “Cancer Models: Systems for Identifying New Drugs Are Often Faulty,” [cited by applicant]
Halford, “Amgen unveils its Kras covalent inhibitor AMG 510,” [cited by applicant]
Hallin, et al., “The KRAS [cited by applicant]
Hansen, et al., “Abstract 686: Drugging an undruggable pocket: the biochemical mechanism of covalent KRAS [cited by applicant]
Hichri, et al., “A Convenient Synthesis of 1,3,2-Benzodiazaphophorine-2-Oxide,” [cited by applicant]
Hichri, et al., CAPLUS Abstract, 162:245378 (2015). [cited by applicant]
Hocker, et al., “Andrographolide derivatives inhibit guanine nucleotide exchange and abrogate oncogenic Ras function,” [cited by applicant]
Huang, et al., “Epidermal Growth Factor Receptor Blockade with C225 Modulates Proliferation, Apoptosis, and Radiosensitivity in Squamous Cell Carcinomas of the Head and Neck,” [cited by applicant]
International Search Report for PCT/US2017/067801, mailed Jul. 25, 2018, 6 pages. [cited by applicant]
International Search Report for PCT/US2018/033714, mailed Jul. 17, 2018, 3 pages. [cited by applicant]
International Search Report for PCT/US2018/050044, mailed Oct. 30, 2018, 7 pages. [cited by applicant]
International Search Report for PCT/US2019/030593, mailed Aug. 6, 2019, 4 pages. [cited by applicant]
International Search Report for PCT/US2019/030606, mailed Jul. 23, 2019, 5 pages. [cited by applicant]
International Search Report for PCT/US2019/031535, mailed Jul. 25, 2019, 7 pages. [cited by applicant]
International Search Report for PCT/US2019/034974, mailed Aug. 9, 2019, 5 pages. [cited by applicant]
International Search Report for PCT/US2019/036397, mailed Aug. 26, 2019, 5 pages. [cited by applicant]
International Search Report for PCT/US2019/036626, mailed Jun. 2, 2020, 5 pages. [cited by applicant]
International Search Report for PCT/US2019/061815, mailed Mar. 5, 2020, 6 pages. [cited by applicant]
International Search Report for PCT/US2019/062051, mailed Mar. 2, 2020, 3 pages. [cited by applicant]
International Search Report for PCT/US2020/032686, mailed Aug. 14, 2020, 4 pages. [cited by applicant]
International Search Report for PCT/US2020/033831, mailed Jul. 9, 2020, 6 pages. [cited by applicant]
International Search Report for PCT/US2020/033832, mailed Jul. 8, 2020, 4 pages. [cited by applicant]
Janes, et al., “Targeting KRAS Mutant Cancers with a Covalent G12C-Specific Inhibitor,” [cited by applicant]
Jarvis, “Notorious KRAS: Taking down cancer researchers' biggest foe,” [cited by applicant]
Jin, et al., “Inhibition of AKT survival pathway by a small molecule inhibitor in human endometrial cancer cells,” [cited by applicant]
Johnson et al., “Relationships between drug activity in NCI preclinical in vitro and in vivo models and early clinical trials,” [cited by applicant]
Lanman, et al., “Abstract 4455: Discovery of AMG 510, a first-in-human covalent inhibitor of KRAS [cited by applicant]
Lanman, et al., “Abstract 4455: Discovery of AMG 510, a first-in-human covalent inhibitor of KRAS [cited by applicant]
Lanman, et al., “Discovery of a Covalent Inhibitor of KRAS [cited by applicant]
Li, et al., “Targeting Protein-Protein Interaction with Covalent Small-Molecule Inhibitors,” [cited by applicant]
Lim, et al., “Therapeutic Targeting of Oncogenic K-Ras by a Covalent Catalytic Site Inhibitor,” [cited by applicant]
Lipford, et al., “Pre-Clinical Development of AMG 510: The First Inhibitor of KRAS [cited by applicant]
Liu, Y., “Session SY28—Transformative Small Molecule Therapies—Targeting KRAS mutant cancers with a covalent G12C—specific inhibitor,” Presentation on Apr. 4, 2017, AACR Annual Meeting Presentation, Apr. 1-5, 2017, Wash… [cited by applicant]
Lopez, et al., “Optimization of quinazolinone-based covalent inhibitors of KRAS [cited by applicant]
Lu, et al., “KRAS G12C Drug Development: Discrimination between Switch II Pocket Configurations Using Hydrogen/Deuterium-Exchange Mass Spectrometry,” [cited by applicant]
Maurer, et al., “Small-molecule ligands bind to a distinct pocket in Rad and inhibit SOS-mediated nucleotide exchange activity,” [cited by applicant]
McGregor, et al., “Expanding the Scope of Electrophiles Capable of Targeting K-Ras Oncogenes,” [cited by applicant]
Mirati Therapeutics, “Corporate Presentation Nov. 2017,” Slides 1-41 (2017). [cited by applicant]
Modjtahedi, et al., “The human EGF receptor as a target for cancer therapy: six new rat mAbs AGainst the receptor on the breast carcinoma MDA-MB 468,” [cited by applicant]
Morrissey et al., “Immunotherapy and Novel Combinations in Oncology: Current Landscape, Challenges, and Opportunities,” [cited by applicant]
National Cancer Institute identifier: NSC 154020, retrieved on Nov. 29, 2018, from https://cactus.nci.nih.gov/ncidb2.2/. [cited by applicant]
NCBI Reference Sequence, “GTPase KRas isoform a [ [cited by applicant]
Non-Final Office Action (Corrected) for U.S. Appl. No. 16/125,359, mailed Apr. 8, 2019, 13 pages. [cited by applicant]
Non-Final Office Action for U.S. Appl. No. 15/849,905, mailed Mar. 20, 2019, 18 pages. [cited by applicant]
Non-Final Office Action for U.S. Appl. No. 15/984,855, mailed Sep. 27, 2018, 25 pages. [cited by applicant]
Non-Final Office Action for U.S. Appl. No. 16/125,359, mailed Apr. 5, 2019, 13 pages. [cited by applicant]
Non-Final Office Action for U.S. Appl. No. 16/402,538, mailed Oct. 30, 2019, 12 pages. [cited by applicant]
Non-Final Office Action for U.S. Appl. No. 16/402,589, mailed Mar. 6, 2020, 17 pages. [cited by applicant]
Non-Final Office Action for U.S. Appl. No. 16/407,889, mailed Jul. 1, 2020, 6 pages. [cited by applicant]
Non-Final Office Action for U.S. Appl. No. 16/428,163, mailed Sep. 15, 2020, 6 pages. [cited by applicant]
Non-Final Office Action for U.S. Appl. No. 16/436,647, mailed Aug. 7, 2020, 19 pages. [cited by applicant]
Non-Final Office Action for U.S. Appl. No. 16/438,349, mailed Dec. 13, 2019, 15 pages. [cited by applicant]
Non-Final Office Action for U.S. Appl. No. 16/661,907, mailed Nov. 18, 2019, 20 pages. [cited by applicant]
Notice of Allowance mailed Jul. 24, 2020 for U.S. Appl. No. 16/402,538, 8 pages. [cited by applicant]
Notice of Allowance mailed Sep. 16, 2020 for U.S. Appl. No. 16/402,589, 5 pages. [cited by applicant]
Notice of Allowance mailed Sep. 9, 2020 for U.S. Appl. No. 16/438,349, 9 pages. [cited by applicant]
Ostrem, et al., “Development of mutant-specific small molecule inhibitors of K-Ras,” Poster, AACR 104th Annual Meeting 2013; Apr. 6-10, 2013; Washington, D.C. (2013). [cited by applicant]
Ostrem, et al., “K-Ras(G12C) inhibitors allosterically control GTP affinity and effector interactions,” [cited by applicant]
Paez, et al., “EGFR Mutations in Lung Cancer Correlation with Clinical Response to Gefitinib Therapy,” [cited by applicant]
Palmioli, et al., “First experimental identification of Ras-inhibitor binding interface using a water-soluble Ras ligand,” [cited by applicant]
Patricelli, et al., “Selective Inhibition of Oncogenic KRAS Output with Small Molecules Targeting the Inactive State,” [cited by applicant]
Pearce, et al., “Failure modes in anticancer drug discovery and development,” [cited by applicant]
Peri, et al., “Design, Synthesis and Biological Evaluation of Sugar-Derived Ras Inhibitors,” [cited by applicant]
Peri, et al., “Sugar-Derived Ras Inhibitors: Group Epitope Mapping by NMR Spectroscopy and Biological Evaluation,” [cited by applicant]
Peters, et al., “Selective inhibition of K-Ras G12C through allosteric control of GTP affinity and effector interactions,” EORTC Poster (2013). [cited by applicant]
Remington's Pharmaceutical Sciences, 1435-1712 (18th ed., Mack Publishing Co, Easton, Pennsylvania, 1990 (Table of Contents Only). [cited by applicant]
Rex et al., “KRAS—AACR 2018,” Amgen Collection of Information published at Proceedings of the American Association for Cancer Research Annual Meeting 2018; Apr. 14-18, 2018; Chicago, IL; AACR; slides 1-24 (2018). [cited by applicant]
Rex, et al., “Abstract 3090: In vivo characterization of AMG 510—a potent and selective KRAS [cited by applicant]
Rex, et al., “Abstract 3090: In vivo characterization of AMG 510—a potent and selective KRAS [cited by applicant]
Saiki, et al., “Abstract 4484: Discovery and in vitro characterization of AMG 510—a potent and selective covalent small-molecule inhibitor of KRAS [cited by applicant]
Saiki, et al., “Abstract 4484: Discovery and in vitro characterization of AMG 510—a potent and selective covalent small-molecule inhibitor of KRAS [cited by applicant]
Sarkar, et al., “Indole-3-Carbinol and Prostate Cancer [cited by applicant]
Shima, et al., “In silico discovery of small-molecule Ras inhibitors that display antitumor activity by blocking the Ras-effector interaction,” [cited by applicant]
Simone, “Part XIV Oncology: Introduction,” [cited by applicant]
Singh, et al., “Improving Prospects for Targeting RAS,” [cited by applicant]
Statsyuk, “Let K-Ras activate its own inhibitor,” [cited by applicant]
Sun, et al., “Discovery of Small Molecules that Bind to K-Ras and Inhibit Sos-Mediated Activation,” [cited by applicant]
Taveras, et al., “Ras Oncoprotein Inhibitors: The Discovery of Potent, Ras Nucleotide Exchange Inhibitors and the Structural Determination of a Drug-Protein Complex,” [cited by applicant]
Teramoto, et al., 1996, Cancer 77 (4):639-645. [cited by applicant]
The ASCO Post Staff, “AACR-NCI-EORTC: Investigational KRAS G12C Inhibitor for KRAS-Mutant Solid Tumors,” The ASCO Post (2019). [cited by applicant]
Thompson, et al., “PD-1 Is Expressed by Tumor-Infiltrating Immune Cells and Is Associated with Poor Outcome for Patients with Renal Cell Carcinoma,” [cited by applicant]
Traxler, “Tyrosine kinase inhibitors in cancer treatment (Part II),” [cited by applicant]
U.S. Appl. No. 60/528,340, filed Dec. 9, 2003. [cited by applicant]
Wang, et al., “Ras inhibition via direct Ras binding—is there a path forward?,” [cited by applicant]
Written Opinion for PCT/US2017/067801, mailed Jul. 25, 2018, 10 pages. [cited by applicant]
Written Opinion for PCT/US2018/033714, mailed Jul. 17, 2018, 5 pages. [cited by applicant]
Written Opinion for PCT/US2018/050044, mailed Oct. 30, 2018, 7 pages. [cited by applicant]
Written Opinion for PCT/US2019/030593, mailed Aug. 6, 2019, 5 pages. [cited by applicant]
Written Opinion for PCT/US2019/030606, mailed Jul. 23, 2019, 6 pages. [cited by applicant]
Written Opinion for PCT/US2019/031535, mailed Jul. 25, 2019, 7 pages. [cited by applicant]
Written Opinion for PCT/US2019/034974, mailed Aug. 9, 2019, 5 pages. [cited by applicant]
Written Opinion for PCT/US2019/036397, mailed Aug. 26, 2019, 5 pages. [cited by applicant]
Written Opinion for PCT/US2019/036626, mailed Jun. 2, 2020, 12 pages. [cited by applicant]
Written Opinion for PCT/US2019/061815, mailed Mar. 5, 2020, 4 pages. [cited by applicant]
Written Opinion for PCT/US2019/062051, mailed Mar. 2, 2020, 5 pages. [cited by applicant]
Written Opinion for PCT/US2020/032686, mailed Aug. 14, 2020, 6 pages. [cited by applicant]
Written Opinion for PCT/US2020/033831, mailed Jul. 9, 2020, 7 pages. [cited by applicant]
Written Opinion for PCT/US2020/033832, mailed Jul. 8, 2020, 6 pages. [cited by applicant]
Xiong, et al., “Covalent Guanosine Mimetic Inhibitors of G12C KRAS,” [cited by applicant]
Yan, et al., “Pharmacogenetics and pharmacogenomics in oncology therapeutic antibody development,” [cited by applicant]
Yang, et al., “Akt/Protein Kinase B Signaling Inhibitor-2, a Selective Small Molecule Inhibitor of Akt Signaling with Antitumor Activity in Cancer Cells Overexpressing Akt,” [cited by applicant]
Yang, et al., “Eradication of Established Tumors by a Fully Human Monoclonal Antibody to the Epidermal Growth Factor Receptor without Concomitant Chemotherapy,” [cited by applicant]
Zeng, et al., “Potent and Selective Covalent Quinazoline Inhibitors of KRAS G12C,” [cited by applicant]
Zimmerman, et al., “Small molecule inhibition of the KRAS-PDEδ interaction impairs oncogenic KRAS signaling,” [cited by applicant]
International Search Report for PCT/US2019/62064, mailed Oct. 29, 2020, 9 pages. [cited by applicant]
Written Opinion for PCT/US2019/62064, mailed Oct. 29, 2020, 13 pages. [cited by applicant]
Hong, et al., “KRAS [cited by applicant]
AMG-510; CS-0081316; Source: AbaChemScene (CS-0081316); Deposit Date: May 13, 2019 Available Date: May 13, 2019; SID: 384060804[CID: 137278711] (available at https://pubchem.ncbi.nlm.nih.gov/substance/384060804/). [cited by applicant]
AMG-510; HY-114277; Source: MedChemexpress MCE (HY-114277); Deposit Date: May 13, 2019 Available Date: May 13, 2019; SID: 384060569[CID: 137278711] (available at https://pubchem.ncbi.nlm.nih.gov/substance/384060569). [cited by applicant]
Canon, et al., “The clinical KRAS(G12C) inhibitor AMG 510 drives anti-tumour immunity,” [cited by applicant]
Database Registry [Online], Chemical Abstracts Service, Columbus, Ohio, US; Jul. 31, 2017 (Jul. 31, 2017), XP002801805, retrieved from STN Database accession No. 2105944-09-8. [cited by applicant]
Final Office Action for U.S. Appl. No. 16/436,647, mailed Mar. 24, 2021, 7 pages. [cited by applicant]
Meanwell, “Synopsis of Some Recent Tactical Application of Bioisosteres in Drug Design,” [cited by applicant]
Non-Final Office Action for U.S. Appl. No. 16/675,121, mailed Feb. 2, 2021, 10 pages. [cited by applicant]
Non-Final Office Action for U.S. Appl. No. 16/817,109, mailed Mar. 3, 2021, 12 pages. [cited by applicant]
Notice of Allowance mailed Jan. 14, 2021 for U.S. Appl. No. 16/402,589, 5 pages. [cited by applicant]
Cited By (2)
US 12,692,266 US 12,735,419