| Date | Name | Title | Type | Security | Shares | Price | Value | Ownership | Reported |
| 10/03/2017 | JENKINSON PAUL L | CFO | Disposition | Common Stock | 9.5k | $0.00 | $0 | | 10/03/2017 |
| 10/03/2017 | JENKINSON PAUL L | CFO | Disposition | Common Stock | 3k | $180.00 | $540k | See footnote | 10/03/2017 |
| 10/03/2017 | JENKINSON PAUL L | CFO | Disposition | Employee Stock Option (Right to Buy) | 41.7k | $45.04 | $1.9M | | 10/03/2017 |
| 10/03/2017 | JENKINSON PAUL L | CFO | Disposition | Employee Stock Option (Right to Buy) | 83.3k | $45.04 | $3.8M | | 10/03/2017 |
| 10/03/2017 | JENKINSON PAUL L | CFO | Disposition | Employee Stock Option (Right to Buy) | 24.2k | $46.09 | $1.1M | | 10/03/2017 |
| 10/03/2017 | DOUMANI ROY | Director | Other | Common Stock | 150.6k | $180.00 | $27.1M | | 10/03/2017 |
| 10/03/2017 | DOUMANI ROY | Director | Disposition | Common Stock | 1.8k | $0.00 | $0 | | 10/03/2017 |
| 10/03/2017 | DOUMANI ROY | Director | Other | Common Stock | 25.1k | $180.00 | $4.5M | By spouse | 10/03/2017 |
| 10/03/2017 | DOUMANI ROY | Director | Disposition | Director Stock Option (Right to Buy) | 30k | $6.89 | $206.7k | | 10/03/2017 |
| 10/03/2017 | DOUMANI ROY | Director | Disposition | Director Stock Option (Right to Buy) | 10k | $59.23 | $592.3k | | 10/03/2017 |
| 10/03/2017 | DOUMANI ROY | Director | Disposition | Director Stock Option (Right to Buy) | 7k | $50.87 | $356.1k | | 10/03/2017 |
| 10/03/2017 | DOUMANI ROY | Director | Disposition | Director Stock Option (Right to Buy) | 8.8k | $91.21 | $803.6k | | 10/03/2017 |
| 09/25/2017 | Chang David D | EVP, R&D, Chief Medical Off. | Grant | Common Stock | 15k | $0.00 | $0 | | 09/25/2017 |
| 09/25/2017 | Chang David D | EVP, R&D, Chief Medical Off. | Sale | Common Stock | 7.9k | $179.66 | $1.4M | | 09/25/2017 |
| 09/25/2017 | JENKINSON PAUL L | CFO | Grant | Common Stock | 2.5k | $0.00 | $0 | | 09/25/2017 |
| 09/25/2017 | JENKINSON PAUL L | CFO | Sale | Common Stock | 948 | $179.66 | $170.3k | | 09/25/2017 |
| 09/25/2017 | Tomasello Shawn | Chief Commercial Officer | Grant | Common Stock | 4.5k | $0.00 | $0 | | 09/25/2017 |
| 09/25/2017 | Tomasello Shawn | Chief Commercial Officer | Sale | Common Stock | 4.2k | $179.66 | $755.1k | | 09/25/2017 |
| 09/25/2017 | Wiezorek Jeffrey | SVP Clinical Development | Grant | Common Stock | 10k | $0.00 | $0 | | 09/25/2017 |
| 09/25/2017 | Wiezorek Jeffrey | SVP Clinical Development | Sale | Common Stock | 5.3k | $179.66 | $949.2k | | 09/25/2017 |
| 09/25/2017 | MOORE TIMOTHY L. | EVP, Technical Operations | Grant | Common Stock | 8k | $0.00 | $0 | | 03/15/2017 |
| 09/25/2017 | MOORE TIMOTHY L. | EVP, Technical Operations | Sale | Common Stock | 4.2k | $179.66 | $759.6k | | 03/15/2017 |
| 08/10/2017 | BUTITTA CYNTHIA M | COO | Sale | Common Stock | 5.8k | $121.03 | $702k | | 08/10/2017 |
| 08/10/2017 | BUTITTA CYNTHIA M | COO | Exercise | Employee Stock Option (Right to Buy) | 15k | $1.35 | $20.2k | | 08/10/2017 |
| 08/10/2017 | BUTITTA CYNTHIA M | COO | Sale | Common Stock | 9.2k | $120.52 | $1.1M | | 08/10/2017 |
| 08/10/2017 | Kim Helen Susan | EVP, Business Development | Sale | Common Stock | 6.3k | $120.09 | $750.7k | | 08/10/2017 |
| 08/10/2017 | Kim Helen Susan | EVP, Business Development | Exercise | Employee Stock Option (Right to Buy) | 3.6k | $53.90 | $193.8k | | 08/10/2017 |
| 08/10/2017 | Kim Helen Susan | EVP, Business Development | Exercise | Employee Stock Option (Right to Buy) | 2.7k | $51.43 | $136.6k | | 08/10/2017 |
| 08/08/2017 | Kim Helen Susan | EVP, Business Development | Sale | Common Stock | 11.1k | $115.02 | $1.3M | | 08/08/2017 |
| 08/08/2017 | Kim Helen Susan | EVP, Business Development | Sale | Common Stock | 1.7k | $117.27 | $199.4k | | 08/08/2017 |
| 08/08/2017 | Kim Helen Susan | EVP, Business Development | Sale | Common Stock | 3.8k | $118.61 | $450.7k | | 08/08/2017 |
| 08/08/2017 | Kim Helen Susan | EVP, Business Development | Sale | Common Stock | 18.9k | $119.94 | $2.3M | | 08/08/2017 |
| 08/08/2017 | Kim Helen Susan | EVP, Business Development | Sale | Common Stock | 31.2k | $120.40 | $3.8M | | 08/08/2017 |
| 08/08/2017 | Kim Helen Susan | EVP, Business Development | Sale | Common Stock | 13.3k | $121.37 | $1.6M | | 08/08/2017 |
| 08/08/2017 | Kim Helen Susan | EVP, Business Development | Exercise | Employee Stock Option (Right to Buy) | 79.9k | $53.90 | $4.3M | | 08/08/2017 |
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