SC TO-T/A

SECURITIES AND EXCHANGE COMMISSION

WASHINGTON, D.C.  20549

SCHEDULE TO

(Rule 14d-100)

TENDER OFFER STATEMENT UNDER SECTION 14(d)(1) OR 13(e)(1)

OF THE SECURITIES EXCHANGE ACT OF 1934

(Amendment No. 12)

CYPRESS BIOSCIENCE, INC.

(Name of Subject Company (Issuer))

RAMIUS V&O ACQUISITION LLC

RAMIUS VALUE AND OPPORTUNITY ADVISORS LLC

RAMIUS VALUE AND OPPORTUNITY MASTER FUND LTD

RAMIUS NAVIGATION MASTER FUND LTD

RAMIUS OPTIMUM INVESTMENTS LLC

COWEN OVERSEAS INVESTMENT LP

RAMIUS ENTERPRISE MASTER FUND LTD

RAMIUS ADVISORS, LLC

COWEN GROUP, INC.

RCG HOLDINGS LLC

RAMIUS LLC

C4S & CO., L.L.C.

ROYALTY PHARMA US PARTNERS 2008, LP

ROYALTY PHARMA US PARTNERS, LP

ROYALTY PHARMA CAYMAN PARTNERS, LP

ROYALTY PHARMA CAYMAN PARTNERS 2008, L.P.

RP INVESTMENT CORP.

PHARMACEUTICAL INVESTORS, LP

PHARMA MANAGEMENT, LLC

RP MANAGEMENT, LLC

(Names of Filing Persons (Offerors))

Common Stock, Par Value $0.001 Per Share

(Title of Class of Securities)

232674507

(CUSIP Number of Class of Securities)

JEFFREY C. SMITH

RAMIUS VALUE AND OPPORTUNITY ADVISORS LLC

599 Lexington Avenue, 20th Floor

New York, New York 10022

(212) 845-7900

and

Pablo Legorreta

110 East 59th Street

Suite 3300

New York, NY 10022

(212) 883-0200

(Name, Address and Telephone Number of Person

Authorized to Receive Notices and Communications on Behalf of Filing Persons)

Copies to:

STEVE WOLOSKY, ESQ.

OLSHAN GRUNDMAN FROME ROSENZWEIG & WOLOSKY LLP

Park Avenue Tower

65 East 55th Street

New York, New York 10022

(212) 451-2300

and

GEORGE W. LLOYD, ESQ.

GOODWIN PROCTER LLP

Exchange Place

53 State Street

Boston, Massachusetts 02109

(617) 570-1000

CALCULATION OF FILING FEE

Transaction Valuation*	Amount of Filing Fee**
$226,025,735	$16,115.64

_________

* Estimated for purposes of calculating the amount of filing fee only. Transaction value  derived by multiplying 34,773,190 (the maximum number of shares of common stock of  subject company estimated to be acquired by Offeror) by $6.50 (the purchase price per  share offered by Offeror).  Such number of shares of common stock represents  38,588,190 shares issued and outstanding as of November 5, 2010 less 3,815,000 shares  of common stock already owned by Ramius V&O Acquisition LLC and its affiliates.

** The amount of the filing fee, calculated in accordance with Rule 0-11 of the Securities Exchange Act of 1934, as amended, equals $71.30 per $1,000,000 of the value of the transaction.

ý Check the box if any part of the fee is offset as provided by Rule 0-11(a)(2) and identify the filing with which the offsetting fee was previously paid.  Identify the previous filing by registration statement number, or the Form or Schedule and the date of its filing.

Amount Previously Paid:	$10,537.15
Form or Registration No.:	SC TO-T
Filing Party:	Ramius V&O Acquisition LLC
	Ramius Value and Opportunity Advisors LLC
Date Filed:	September 15, 2010
Amount Previously Paid:	$5,578.49
Form or Registration No.:	SC TO-T
Filing Party:	Ramius V&O Acquisition LLC
	Ramius Value and Opportunity Advisors LLC
Date Filed:	December 15, 2010

¨ Check the box if the filing relates solely to preliminary communications made before the commencement of a tender offer.

Check the appropriate boxes below to designate any transactions to which the statement relates:

ý third-party tender offer subject to Rule 14d-1.

¨ issuer tender offer subject to Rule 13e-4.

¨ going-private transaction subject to Rule 13e-3.

¨ amendment to Schedule 13D under Rule 13d-2.

Check the following box if the filing is a final amendment reporting the results of the tender offer:  ¨

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SCHEDULE TO

This Amendment No. 12 to Schedule TO (this “Amendment No. 12”) amends and supplements the Tender Offer Statement on Schedule TO filed with the Securities and Exchange Commission on September 15, 2010, as amended by Amendment No. 1 to Schedule TO filed on September 20, 2010, Amendment No. 2 to Schedule TO filed on September 21, 2010, Amendment No. 3 to Schedule TO filed on September 30, 2010, Amendment No. 4 to  Schedule TO filed on October 12, 2010, Amendment No. 5 to Schedule TO filed on October 14, 2010, Amendment No. 6 to Schedule TO filed on November 3, 2010, Amendment No. 7 to Schedule TO filed on December 10, 2010, Amendment No. 8 to the Schedule TO filed on December 14, 2010, Amendment No. 9 to the Schedule TO filed on December 15, 2010, Amendment No. 10 to the Schedule TO filed on December 20, 2010 a nd Amendment No. 11 to the Schedule TO filed on December 21, 2010 (collectively, the “Schedule TO”), by Ramius V&O Acquisition LLC, a Delaware limited liability company (“Purchaser”) owned by Ramius Value and Opportunity Advisors LLC, a Delaware limited liability company (“Ramius”), Royalty Pharma US Partners 2008, LP, a Delaware limited partnership (“RP US 2008”), Royalty Pharma US Partners, LP, a Delaware limited partnership (“RP US”), and RP Investment Corp., a Delaware corporation (“RP US Corp”), and certain of their affiliates, including Ramius Value and Opportunity Master Fund Ltd, Ramius Navigation Master Fund Ltd, Ramius Optimum Investments LLC, Cowen Overseas Investment LP, Ramius Enterprise Master Fund Ltd, Ramius Advisors, LLC, Cowen Group, Inc., RCG Holdings LLC, Ramius LLC, C4S & Co., L.L.C., Royalty Pharma Cayman Partners, LP, Royalty Pharma Cayman Partners 2008, L.P., Pharmaceutical Investors, LP, Pharma Management , LLC and RP Management, LLC (collectively, together with Ramius, RP US 2008, RP US, RP US Corp and Purchaser, the “Ramius/RP Group”), relating to the offer by Purchaser (the “Offer”) to purchase all issued and outstanding shares of Common Stock, par value $0.001 per share, together with the associated preferred stock purchase rights (the “Rights,” and together with such shares, the “Shares”), of Cypress Bioscience, Inc., a Delaware corporation (“Cypress”), at a price of $6.50 per Share, net to the seller in cash, without interest and subject to any required withholding of taxes, upon the terms and subject to the conditions set forth in the Amended and Restated Offer to Purchase (the “Offer to Purchase”) dated December 20, 2010, and in the related Letter of Transmittal (the “Letter of Transmittal”), each of which may be amended or supplemented from time to time.  This Amendment No. 12 is being filed on behalf of the Ramius/RP Group.

The information set forth in the Offer to Purchase, including Schedule I thereto, is hereby incorporated by reference in answer to all applicable items of this Amendment No. 12. This Amendment No. 12 should be read together with the Schedule TO.

The Offer is scheduled to expire at 12:00 Midnight, New York City time, on January 5, 2011 unless the Offer is extended.

The safe harbor protections for forward-looking statements contained in the Private Securities Litigation Reform Act of 1995 do not apply to any forward-looking statements Purchaser or its affiliates may make in connection with the Offer.

ITEMS 1 THROUGH 9; ITEM 11.

Item 11 of the Schedule TO is hereby amended and supplemented to add the following:

 “On January 3, 2011, the United States Federal Trade Commission notified the Ramius/RP Group that the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act of 1976, as amended (the “HSR Act”), relating to the Offer had been terminated. Accordingly, the condition to the Offer relating to there being no restrictions or prohibitions under any applicable antitrust laws that would make illegal the consummation of the Offer or the merger contemplated thereby has been satisfied.

The full text of the joint press release issued by Cypress and Ramius V&O Acquisition on January 4, 2011 announcing such early termination is filed as Exhibit (a)(5)(K) hereto and is incorporated by reference.”

ITEM 12. EXHIBITS.

Item 12 of the Schedule TO is hereby amended and supplemented to add the following:

(a)(5)(K) Joint press release issued by Ramius V&O Acquisition LLC and Cypress Bioscience, Inc., dated January 4, 2011.

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SIGNATURE

After due inquiry and to the best of my knowledge and belief, I hereby certify as of January 4, 2011 that the information set forth in this statement is true, complete and correct.

RAMIUS VALUE AND OPPORTUNITY MASTER FUND LTD By: Ramius Value and Opportunity Advisors LLC,        its investment manager   RAMIUS NAVIGATION MASTER FUND LTD By: Ramius Advisors, LLC,        its investment advisor   RAMIUS ENTERPRISE MASTER FUND LTD By: Ramius Advisors, LLC,        its investment advisor   RAMIUS VALUE AND OPPORTUNITY ADVISORS LLC By: Ramius LLC,        its sole member   RAMIUS OPTIMUM INVESTMENTS LLC By: Ramius Advisors, LLC,        its managing member RAMIUS V&O ACQUISITION LLC   COWEN OVERSEAS INVESTMENT LP By: Ramius Advisors, LLC,        its general partner   RAMIUS ADVISORS, LLC By: Ramius LLC,    its sole member   RAMIUS LLC By: Cowen Group, Inc.,         its sole member COWEN GROUP, INC. RCG HOLDINGS LLC By: C4S & Co., L.L.C.,        its managing member   C4S & CO., L.L.C.

By:	/s/ Jeffrey C. Smith
	Jeffrey C. Smith
	Authorized Signatory

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ROYALTY PHARMA US PARTNERS 2008, LP By: Pharmaceutical Investors, LP By: Pharma Management, LLC     ROYALTY PHARMA US PARTNERS, LP By: Pharmaceutical Investors, LP By: Pharma Management, LLC       ROYALTY PHARMA CAYMAN PARTNERS, LP By: Pharmaceutical Investors, LP By: Pharma Management, LLC   ROYALTY PHARMA CAYMAN PARTNERS 2008, L.P. By: Pharmaceutical Investors, LP By: Pharma Management, LLC   RP INVESTMENT CORP.     PHARMACEUTICAL INVESTORS, LP By: Pharma Management, LLC     PHARMA MANAGEMENT, LLC   RP MANAGEMENT, LLC    

By:	/s/ Pablo Legoretta
	Pablo Legoretta
	Authorized Signatory

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EXHIBIT INDEX

Exhibit No.	Description
(a)(1)(A)	Offer to Purchase, dated September 15, 2010.*
(a)(1)(B)	Letter of Transmittal (including Guidelines for Certification of Taxpayer Identification Number on Substitute Form W-9).*
(a)(1)(C)	Notice of Guaranteed Delivery.*
(a)(1)(D)	Letter to Brokers, Dealers, Commercial Banks, Trust Companies and other Nominees.*
(a)(1)(E)	Form of Letter to Clients for use by Brokers, Dealers, Commercial Banks, Trust Companies and Nominees.*
(a)(1)(F)	Summary Advertisement published on September 15, 2010.*
(a)(1)(G)	Amended and Restated Offer to Purchase, dated December 20, 2010. †
(a)(1)(H)	Amended and Restated Letter of Transmittal (including Guidelines for Certification of Taxpayer Identification Number on Substitute Form W-9). †
(a)(1)(I)	Amended and Restated Notice of Guaranteed Delivery. †
(a)(1)(J)	Amended and Restated Letter to Brokers, Dealers, Commercial Banks, Trust Companies and other Nominees. †
(a)(1)(K)	Amended and Restated Form of Letter to Clients for use by Brokers, Dealers, Commercial Banks, Trust Companies and Nominees. †
(a)(5)(A)	Press release issued by Ramius LLC, dated September 15, 2010, announcing the commencement of the Offer.*
(a)(5)(B)	Press release issued by Ramius Value and Opportunity Advisors LLC, dated September 17, 2010. *
(a)(5)(C)	Press release issued by Ramius Value and Opportunity Advisors LLC, dated September 21, 2010.*
(a)(5)(D)	Press release issued by Ramius Value and Opportunity Advisors LLC, dated September 30, 2010. *
(a)(5)(E)	Content of www.tenderforcypressbio.com. *
(a)(5)(F)	Press release issued by Ramius Value and Opportunity Advisors LLC, dated October 11, 2010. *
(a)(5)(G)	Press release issued by Ramius Value and Opportunity Advisors LLC, dated November 2, 2010. *
(a)(5)(H)	Press release issued by Ramius Value and Opportunity Advisors LLC, dated December 10, 2010 *
(a)(5)(I)	Joint press release issued by Ramius V&O Acquisition LLC and Cypress Bioscience, Inc., dated December 15, 2010 (incorporated by reference to Exhibit 99.1 to the Current Report on Form 8-K filed by Cypress Bioscience, Inc. with the Commission on December 15, 2010).
(a)(5)(J)	Press release issued by Ramius V&O Acquisition LLC, dated December 21, 2010.*
(a)(5)(K)	Joint press release issued by Ramius V&O Acquisition LLC and Cypress Bioscience, Inc., dated January 4, 2011. †
(d)(1)	Joint Filing Agreement by and among Ramius Value and Opportunity Master Fund Ltd, Ramius Navigation Master Fund Ltd, Ramius Optimum Investments LLC, Cowen Overseas Investment LP, Ramius Enterprise Master Fund Ltd, Ramius Advisors, LLC, RCG Starboard Advisors, LLC, Ramius LLC, Cowen Group, Inc., RCG Holdings LLC, C4S & Co., L.L.C., Peter A. Cohen, Morgan B. Stark, Thomas W. Strauss and Jeffrey M. Solomon, dated July 19, 2010 (incorporated by reference to the Schedule 13D filed by Ramius LLC with the Securities and Exchange Commission on July 19, 2010).
(d)(2)	Agreement and Plan of Merger, dated December 14, 2010, by and among Cypress Bioscience, Inc., Ramius Value and Opportunity Advisors LLC, Royalty Pharma US Partners, LP, Royalty Pharma US Partners 2008, LP, RP Investment Corp. and Ramius V&O Acquisition LLC (incorporated by reference to Exhibit 2.1 to the Current Report on Form 8-K filed by Cypress Bioscience, Inc. with the Commission on December 16, 2010).
(g)	None.
(h)	None.

* Previously filed with the Schedule TO.

† Filed herewith.

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EX-99.(A)(5)(K)

Exhibit (a)(5)(K)

Jan 04, 2011 08:30 ET

FTC Grants Early Termination of Waiting Period Under Hart-Scott-Rodino Act

SAN DIEGO, CA and NEW YORK, NY--(January 4, 2011) - Cypress Bioscience, Inc. (NASDAQ: CYPB) ("Cypress"), a pharmaceutical company engaged in the development of innovative drugs to treat central nervous system disorders, today announced that the Federal Trade Commission has granted early termination of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act of 1976, as amended ("HSR") applicable to the cash tender offer by Ramius V&O Acquisition LLC, an affiliate of Ramius LLC (collectively, "Ramius") and affiliates of Royalty Pharma ("Royalty Pharma" and together with Ramius, the "Ramius/RP Group"), to purchase all of the outstanding shares of common stock of Cypress not already owned by the Ramius/RP Group.

The early termination of the HSR waiting period satisfies one of the conditions necessary for the consummation of the tender offer. The tender offer is scheduled to expire at 11:59 p.m. Eastern time on Wednesday, January 5, 2011 (the end of the day on Wednesday), unless the tender offer is extended. Consummation of the tender offer remains subject to other customary conditions, including the tender of a majority of the outstanding shares of Cypress' common stock, determined on a fully diluted basis.

As previously announced, the Ramius/RP Group amended its tender offer on December 20, 2010, for all of the outstanding shares of common stock for $6.50 per share in cash. The tender offer was made pursuant to an Amended and Restated Offer to Purchase, dated December 20, 2010, and in connection with the Agreement and Plan of Merger, dated December 14, 2010, entered into by and among Cypress, Ramius and Royalty Pharma, which Cypress and the Ramius/RP Group announced on December 14, 2010.

About Cypress

Cypress is a pharmaceutical company dedicated to the development of innovative drugs targeting large unmet medical needs for patients suffering from a variety of disorders of the central nervous system. Since 1999, Cypress has received FDA approvals for both of the products it brought to the FDA during that period, including for Prosorba™, a medical device for rheumatoid arthritis, and Savella® (milnacipran HCl), for fibromyalgia. The Company focuses on generating stockholder value by reaching clinical development milestones as quickly and efficiently as possible. Cypress' development-stage assets include CYP-1020 for cognitive impairment in schizophrenia, Staccato® n icotine for smoking cessation and intranasal carbetocin for autism. More information on Cypress and its products and development assets is available at http://www.cypress.com/.

About Ramius

Ramius LLC is a registered investment advisor that manages assets in a variety of alternative investment strategies. Ramius LLC is headquartered in New York with offices located in London, Luxembourg, Tokyo, Hong Kong and Munich.

About Royalty Pharma

Royalty Pharma is the industry leader in acquiring revenue-producing intellectual property -- principally royalty interests in marketed and late stage biopharmaceutical products with a market value of over $2 billion. Royalty Pharma currently owns a diversified portfolio of royalty interests in several high-quality blockbuster biopharmaceutical products, including Amgen's Neupogen® and Neulasta®, Genentech's Rituxan®, Gilead's Emtriva®, Truvada® and Atripla®, Celgene's Thalomid®, and now Abbott's Humira®. The company has a ten year history of providing value to holders of royalty interests, including its joint $525 million acquisition with Gilead Sciences of Emory University's emtricitabine royalty interest and its acquisitions of approximately 80% of Memorial Sloan Kettering's U.S. and international royalty interests in Neupogen® and Neulasta® for over $400 million. The strong market position enjoyed by the products in which Royalty Pharma owns royalties -- generally the sole or number one product in their therapeuti c classes -- and its revenue diversification are some of the key attributes contributing to the investment grade rating of Royalty Pharma's finance trust, which is further wrapped by a mono-line insurer to "AAA"/"Aaa" by S&P and Moody's. More information on Royalty Pharma is available at www.royaltypharma.com.

Forward Looking Statement

The offer to buy shares of Cypress common stock will be made only pursuant to the amended and restated offer to purchase and related materials that the Ramius/RP Group has filed with the SEC. Cypress stockholders and other investors should read these materials carefully because they contain important information, including the terms and conditions of the offer. These materials and any other documents filed by the Ramius/RP Group or Cypress with the SEC may be obtained free of charge at the SEC's website at www.sec.gov and by contacting Cypress Investor Relations at 858-452-2323. In addition, investors and security holders will be able to obtain free copies of the documents filed with the SEC on Cypress' website at www.cypress.com. Investors and security holders are urged to read the Schedule TO, as amended, and the Schedule 14D-9, as amended, and the other relevant materials before making any investment decision with respect to the Ramius/RP Group tender offer.

Statements in this press release that relate to future results and events are forward-looking statements based on Cypress', Ramius' and Royalty Pharma's current expectations regarding tender offer and transactions contemplated by the merger agreement. Actual results and events in future periods may differ materially from those expressed or implied by these forward-looking statements because of a number of risks, uncertainties and other factors. There can be no assurances that a transaction will be consummated. Other risks, uncertainties and assumptions include the possibility that expected benefits may not materialize as expected; that the transaction may not be timely completed, if at all; that, prior to the completion of the transaction, if at all, Cypress may not satisfy one or more clo sing conditions and other risks that are described in Cypress' Annual Report on Form 10-K for the year ended December 31, 2009 and in its subsequently filed SEC reports. Cypress undertakes any obligation to update these forward-looking statements except to the extent otherwise required by law.

Contacts:

For Cypress

Matthew Sherman or

Dara Silverstein

212-355-4449

Joele Frank, Wilkinson Brimmer Katcher

Amy Bilbija or Bob Marese

212-929-5500

MacKenzie Partners, Inc.

For Ramius

Peter Feld

212-201-4878

or

Gavin Molinelli

212-201-4828

Ramius LLC

For Royalty Pharma

Pablo Legorreta

212-883-2289

Alexander V. Perfall

212-883-2298