AMENDMENT NO. 1 TO SECURITIES PURCHASE AGREEMENT

Exhibit 10.4

EXECUTION COPY

AMENDMENT NO. 1
TO
SECURITIES PURCHASE AGREEMENT

THIS AMENDMENT NO. 1 (the “ Amendment ”), dated January 16, 2009, amends that certain Securities Purchase Agreement, dated as of January 4, 2009 (the “ Agreement ”), by and between La Jolla Pharmaceutical Company, a Delaware corporation (the “ Company ”), and BioMarin Pharmaceutical Inc., a Delaware corporation (the “ Purchaser ”).

RECITALS

A. WHEREAS, the Purchaser and the Company are parties to the Agreement, which provides for the issuance of shares of the Company’s Series B Convertible Preferred Stock on the terms set forth therein;

B. WHEREAS, Exhibit A to the Agreement sets forth the form of Certificate of Designation to be filed with the Delaware Secretary of State to designate the rights, preferences and privileges of the Company’s Series B-1 Convertible Preferred Stock (the “ Certificate ”);

C. WHEREAS, the Certificates of Designation to be filed with respect to the Company’s Series B-2 Convertible Preferred Stock and Series B-3 Convertible Preferred Stock are to be in substantially the form of the Certificate, with any appropriate adjustments needed to reflect the issuance price for such shares;

D. WHEREAS, under the terms of the Certificate, the Series B Convertible Preferred Stock is convertible into Common Stock at an initial ratio of one-for-three ( i.e., three shares of Common Stock for every one share of Series B Convertible Preferred Stock); and

E. WHEREAS, the Company and the Purchaser wish to amend the form of Certificate and certain related terms of the Agreement to change the initial conversion ratio for the Common Stock to one-for-thirty ( i.e., thirty shares of Common Stock for every one share of Series B Convertible Preferred Stock).

Now therefore, in consideration of the foregoing, the parties agree as follows:

1. Section 1.2 of the Agreement is amended and restated in its entirety as follows:

“1.2 Purchase and Sale . Subject to the terms and conditions of this Agreement and the Collaboration Agreement, on the date hereof, the Company agrees to sell to the Purchaser, and the Purchaser agrees to purchase from the Company, 339,104 Shares (the “ Initial Investment ”) at a purchase price per share of $22.1171, in the case of the Initial Closing, or, in the case of a Subsequent Closing (as defined below) at a price per common share equivalent (based on the conversion ratio provided for in the applicable Certificate of Designation, as adjusted) equal to one hundred ten percent (110%) of the average closing price of the Common Stock of the Company as reported on the NASDAQ stock market or such other reporting service as the stock is then quoted if not then quoted on NASDAQ (and if not then traded at the value determined by an investment bank selected consistent with the provisions of Section 14.3 of the Collaboration Agreement), for the ten (10) consecutive trading days commencing five (5) trading days immediately prior to the date the Company has publicly announced the event that triggered such payment ( i.e., the P-Value Achievement, or in the case of such payment where there is no P-Value Achievement, the Company’s first public announcement of the results of the Second Interim Efficacy Analysis or the first public announcement of the approval of an NDA for the Product under Section 7.13 of the Collaboration Agreement (the “ Announcement of Results ”)). Notwithstanding the foregoing, in no event will the price per common equivalent for the Shares issued in a Subsequent Closing (based on the conversion ratio provided for in the applicable Certificate of Designation, as adjusted) be less than $0.73724.

2. Exhibit A, as attached to the Agreement, is hereby amended and restated in its entirety and is replaced with Exhibit A attached to this Amendment. The defined term “ Certificate of Designation ,” as used in the Agreement, shall hereafter be deemed to refer to the Certificate of Designation for the Series B-1 Convertible Preferred Stock attached as Exhibit A to this Amendment.

3. Section 3.3 is hereby amended to substitute 37,301,327 for 37,301,387.

4. Undefined capitalized terms used in this Amendment shall have the meanings ascribed to them in the Agreement.

5. Except as expressly set forth in this Amendment, all other terms of the Agreement shall remain in full force and effect and once this Amendment is executed by the parties hereto, all references in the Agreement to “the Agreement” or “this Agreement,” as applicable, shall refer to the Agreement, as modified by this Amendment.

6. This Amendment shall be governed by and construed in accordance with the laws of the State of California applicable to contracts made and to be performed entirely within such State without regard to conflict of laws principles thereof.

7. This Amendment may be executed in any number of counterparts and each of such counterparts shall for all purposes be deemed to be an original, and all such counterparts shall together constitute but one and the same instrument.

* * *

IN WITNESS WHEREOF, the parties hereto have executed and delivered this Amendment as of the date first above written.

EXHIBIT A

Certificate of Designation

LA JOLLA PHARMACEUTICAL COMPANY

CERTIFICATE OF DESIGNATIONS
OF
SERIES B-1 CONVERTIBLE PREFERRED STOCK

(Pursuant to Section 151 of the Delaware General Corporation Law)

La Jolla Pharmaceutical Company, a Delaware corporation (the “ Corporation ”), in accordance with the provisions of Section 103 of the Delaware General Corporation Law (the “ DGCL ”) does hereby certify that, in accordance with Section 151(g) of the DGCL, the following resolution was duly adopted by the Board of Directors of the Corporation as of December 18, 2008:

RESOLVED, that the Board of Directors of the Corporation pursuant to authority expressly vested in it by the provisions of the Amended and Restated Certificate of Incorporation of the Corporation, hereby authorizes the issuance of a series of preferred stock designated as the Series B-1 Convertible Preferred Stock, par value $0.01 per share, of the Corporation and hereby fixes the designation, number of shares, powers, preferences, rights, qualifications, limitations and restrictions thereof (in addition to any provisions set forth in the Amended and Restated Certificate of Incorporation of the Corporation which are applicable to the preferred stock of all classes and series) as follows:

SERIES B-1 CONVERTIBLE PREFERRED STOCK

1.  Designation, Amount and Par Value . The series of preferred stock shall be designated as the Corporation’s Series B-1 Convertible Preferred Stock (the “ Series B-1 Preferred Stock ”), and the number of shares so designated shall be 339,104. Each share of Series B-1 Preferred Stock shall have a par value of $0.01 per share.

2.  Liquidation; Dissolution or Winding Up . In the event of any liquidation (other than a liquidation following an M&A Event (as defined below)), dissolution or winding up (either voluntary or involuntary) of the Corporation, subject to the rights of any series of Preferred Stock or other class of stock of the Corporation whose terms expressly provide that it ranks senior to the Series B-1 Preferred Stock as to dividends and distributions, upon dissolution or winding up of the Corporation (the “ Senior Stock ”), the holders of Series B-1 Preferred Stock shall be entitled to receive, prior and in preference to any distribution of any of the assets of the Corporation to the holders of the Corporation’s common stock, par value $0.01 per share (the “ Common Stock ”) and pari passu with any distribution of any of the assets of the Corporation to the holders of any other series of Preferred Stock or other class of stock of the Corporation whose terms expressly provide that they rank pari passu with the Series B-1 Preferred Stock as to dividends and distributions upon the liquidation, dissolution or winding up of the Corporation (“ Parity Stock ”) by reason of their ownership thereof, an amount per share equal to the sum of (i) $22.1171, plus (ii) an amount equal to accrued but unpaid dividend