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                                                                     Exhibit 4.1

                                 SUPERGEN, INC.
                          REGISTRATION RIGHTS AGREEMENT

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                  THIS REGISTRATION RIGHTS AGREEMENT (this "Registration Rights
Agreement") is entered into as of the 15th day of December, 1999, by and among
SUPERGEN, INC., a Delaware corporation (the "Company"), and AVI BIOPHARMA, INC.,
an Oregon corporation ("Investor"), in connection with the purchase of certain
shares of the Company's common stock (the "Common Shares") under the terms of
that certain Subscription Agreement of even date herewith (the "Subscription
Agreement"). The Common Shares shall be referred to hereinafter as the
"Registrable Securities."



                                    RECITALS

                  WHEREAS, the Company proposes to sell the Shares pursuant to
the Subscription Agreement;

                  WHEREAS, as a condition of entering into the Subscription
Agreement, the Investor has requested that the Company extend to it certain
registration rights and other rights as set forth below; and

                  WHEREAS, promptly after the Closing under the Subscription
Agreement, the Company shall file a registration statement with the Securities
and Exchange Commission relating to the Shares.

                  NOW, THEREFORE, in consideration of the mutual promises,
representations, warranties, covenants and conditions set forth in this
Registration Rights Agreement and in the Subscription Agreement, the parties
mutually agree as follows:

             1.   DEFINITIONS. As used in this Registration Rights Agreement the
following terms shall have the following respective meanings:

                  "CLOSING" has the meaning ascribed thereto in the Subscription
Agreement.

                  "EXCHANGE ACT" means the Securities Exchange Act of 1934, as
amended.

                  "FORM S-3" means such form under the Securities Act as in
effect on the date hereof or any successor registration form under the
Securities Act subsequently adopted by the SEC which permits inclusion or
incorporation of substantial information by reference to other documents filed
by the Company with the SEC.

                  "REGISTER," "REGISTERED," and "REGISTRATION" refer to a
registration effected by preparing and filing a registration statement in
compliance with the Securities Act, and the declaration or ordering of
effectiveness of such registration statement.

                  "REGISTRABLE SECURITIES" means the Shares.


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                  "REGISTRATION STATEMENT" means any registration statement of
the Company that covers the Shares pursuant to the provisions of this
Registration Rights Agreement, including the Prospectus included therein, all
amendments and supplements thereto (including post-effective amendments) and all
exhibits and material incorporated by reference or deemed to be incorporated by
reference therein.

                  "SEC" or "COMMISSION" means the Securities and Exchange
Commission.

                  "SECURITIES ACT" shall mean the Securities Act of 1933, as
amended.

         2.       REGISTRATION OF SHARES.

                  2.1 REGISTRATION STATEMENT. Promptly after the Closing, the
Company shall prepare and file with the Commission a Registration Statement on
Form S-3 pursuant to Rule 415 under the Securities Act. In addition, the Company
shall:

                           (a) Use its best efforts to cause such Registration
Statement to become effective as promptly as practicable after the Closing and
to keep such Registration Statement continuously effective for a period of two
years following the date on which the Registration Statement becomes effective
under the Securities Act, or such shorter period ending on the earlier of the
date (i) when all Registrable Securities covered by this Registration Statement
have been sold or (ii) when all Registrable Securities covered by the
Registration Statement may be sold without registration under the Securities Act
pursuant to the exemptions provided by Rule 144 under the Securities Act (and
are not restricted as to volume) (the "Registration Period").

                           (b) Prepare and file with the SEC such pre-effective
and post-effective amendments and supplements to such Registration Statement and
the prospectus used in connection with such Registration Statement as may be
necessary to cause the Registration Statement to become effective, to keep the
Registration Statement continuously effective during the Registration Period and
not misleading, and as may otherwise be required or applicable under, and to
comply with the provisions of, the Securities Act with respect to the
disposition of all securities covered by such Registration Statement during the
Registration Period.

                           (c) Furnish to the Investor such number of copies of
a prospectus, including a preliminary prospectus, and each amendment or
supplement thereto, in conformity with the requirements of the Securities Act,
and such other documents as they may reasonably request in order to facilitate
the disposition of Registrable Securities owned by them.

                           (d) Use its best efforts to register and qualify the
securities covered by such Registration Statement under such other securities or
Blue Sky laws of such jurisdictions as shall be necessary to permit the sale of
the Registrable Securities.

                           (e) Notify promptly the Investor (and in the case of
(i)(A) in no event less than two business days prior to such filing) and (if
requested) confirm such notice in writing, (i)(A) when a prospectus or any
prospectus supplement or post-effective amendment is proposed to be filed, and
(B) with respect to a Registration Statement or any post-effective amendment,
when the same has become effective, (ii) of any request by the SEC or any other
federal or state governmental authority for amendments or supplements to a
Registration Statement or related prospectus or for additional information,
(iii) of the issuance by the SEC of any stop order suspending the effectiveness
of a Registration Statement or the initiation of any proceedings for that
purpose, (iv) of the receipt by the Company of any notification with respect to
the suspension of the


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qualification or exemption from qualification of any of the Registrable
Securities for sale in any jurisdiction, or the initiation or threatening of any
proceeding for such purpose, and (v) of the happening of any event that makes
any statement made in such Registration Statement or related prospectus or any
document incorporated or deemed to be incorporated therein by reference untrue
in any material respect or that requires the making of any changes in such
Registration Statement, prospectus or documents so that, in the case of the
Registration Statement, it will not contain any untrue statement of a material
fact or omit to state any material fact required to be stated therein or
necessary to make the statements therein not misleading, and that in the case of
the prospectus, it will not contain any untrue statement of a material fact or
omit to state any material fact required to be stated therein or necessary to
make the statements therein, in light of the circumstances under which they were
made, not misleading.

                           (f) Use its reasonable best efforts to avoid the
issuance of, or, if issued, obtain the withdrawal of, any order suspending the
effectiveness of a Registration Statement, or the lifting of any suspension of
the qualification (or exemption from qualification) of any of the Registrable
Securities for sale in any jurisdiction, at the earliest practicable moment.

                           (g) If requested by the Investor, (i) promptly
incorporate in a prospectus supplement or post-effective amendment such
information as the Investor reasonably requests should be included therein
regarding Investor or the plan of distribution of the Registrable Securities,
and (ii) make all required filings of the prospectus supplement or such
post-effective amendment as soon as practicable after the Company has received
notification of such matters to be incorporated in such prospectus supplement or
post-effective amendment: PROVIDED, HOWEVER, that the Company shall not be
required to take any action pursuant to this Section 2.1(g) that would, in the
opinion of outside counsel for the Company, violate applicable law.

                           (h) Upon the occurrence of any event contemplated by
Section 2.1(e)(v), as promptly as practicable, prepare a supplement or
amendment, including a post-effective amendment, to each Registration Statement
or a supplement to the related prospectus or any document incorporated or deemed
to be incorporated therein by reference, and file any other required document so
that, as thereafter delivered, such prospectus will not contain an untrue
statement of a material fact or omit to state a material fact required to be
stated therein or necessary to make the statements therein, in light of the
circumstances under which they were made, not misleading.

                           (i) Use its reasonable best efforts to cause all
Registrable Securities relating to such Registration Statement to be listed on
each securities exchange or automated quotation system, if any, on which similar
securities issued by the Company are then listed.

                  2.2 SELLER INFORMATION. The Company may require Investor as to
which any registration is being effected to furnish to the Company such
information regarding Investor, such Investor's Registrable Securities and
Investor's intended method of disposition as the Company may from time to time
reasonably request; PROVIDED that such information shall be used only in
connection with such registration.

                           If the Registration Statement refers to Investor,
then Investor shall promptly (i) notify the Company and its counsel of the
existence of any fact of which Investor becomes aware and the happening of any
event which relates to Investor or the distribution of the securities owned by
Investor which results in the Registration Statement containing an untrue
statement of material fact or omitting to state a material fact required to be
stated therein or necessary to make any statements therein not misleading, or
the Prospectus included in such Registration Statement


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containing an untrue statement of material fact or omitting to state a material
fact required to be stated therein or necessary to make any statements therein,
in light of the circumstances under which they were made, not misleading, and
(ii) provide to the Company such information which relates to Investor or the
distribution of the securities owned by Investor as shall be necessary to enable
the Company to prepare a supplement or post-effective amendment to such
Registration Statement or related Prospectus or any document incorporated
therein by reference or file any other documents required so that such
Registration Statement will not contain any untrue statement of a material fact
or omit to state a material fact required to be stated therein or necessary to
make the statements therein not misleading, and such Prospectus shall not
include an untrue statement of a material fact or omit to state a material fact
required to be stated therein or necessary to make the statements therein, in
light of the circumstances under which they were made, not misleading.

                  2.3 NOTICE TO DISCONTINUE. Investor agrees that, upon receipt
of any notice from the Company of the happening of any event of the kind
described in Section 2.1(e)(ii) through (v), Investor shall forthwith
discontinue disposition of Registrable Securities pursuant to the Registration
Statement covering such Registrable Securities until Investor's receipt of the
copies of the supplemented or amended prospectus contemplated by Section 2.1(h)
and, if so directed by the Company, Investor shall deliver to the Company (at
the Company's expense) all copies, other than permanent file copies, then in
Investor's possession of the Prospectus covering such Registrable Securities
which is current at the time of receipt of such notice.

                  2.4 EXPENSES OF REGISTRATION. Except only as specifically
provided herein, all expenses incident to the performance under or compliance
with this Registration Rights Agreement by the Company shall be borne by the
Company, regardless of whether the Registration Statement becomes effective,
including, without limitation, (i) all registration and filing fees and expenses
(including filings made with the National Association of Securities Dealers
("NASD"), if applicable); (ii) fees and expenses (including fees and expenses of
counsel for the Company) of compliance with federal securities and state Blue
Sky or other securities laws; (iii) expenses of printing, messenger and delivery
services, duplication, word processing and telephone incurred by the Company
(but not by Investor); (iv) fees and disbursements of counsel for the Company;
(v) all application and filing fees in connection with listing Common Shares on
a national securities exchange or automated quotation system pursuant to the
requirements hereof; and (vi) all fees and disbursements of independent
certified public accountants of the Company (including the expenses of any
special audit and "cold comfort" letters required by or incident to such
performance). The Company will, in any event, bear its own internal expenses
(including, without limitation, all salaries and expenses of its officers and
employees performing legal or accounting duties), the expenses of any annual
audit and the fees and expenses of any person, including special experts,
retained by the Company. Investor shall bear its own legal fees and expenses and
any underwriting fees or brokerage commissions incident to their disposition of
the Registered Securities.

                  2.5      INDEMNIFICATION.

                           (a) INDEMNIFICATION BY COMPANY. To the extent
permitted by law, the Company will indemnify and hold harmless Investor, the
partners, officers and directors of Investor and each person, if any, who
controls Investor within the meaning of the Securities Act or the Exchange Act,
against any losses, claims, damages, or liabilities (joint or several) to which
they may become subject under the Securities Act, the Exchange Act or other
federal or state law, insofar as such losses, claims, damages or liabilities (or
actions in respect thereof) arise out of or are based upon any of the following
statements, omissions or violations (collectively a "Violation") by the Company:
(i) any untrue statement or alleged untrue statement of a material fact
contained in the


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Registration Statement or any amendments or supplements thereto, or the omission
or alleged omission to state therein a material fact required to be stated
therein, or necessary to make the statements therein not misleading, (ii) any
untrue statement or alleged untrue statement of a material fact contained in the
Prospectus (including any preliminary, final or summary prospectus, amendment or
supplement thereto) included in such Registration Statement or any omission or
alleged omission to state a material fact required to be stated therein or
necessary to make any statement therein, in light of the circumstances under
which they were made, not misleading, or (iii) any violation or alleged
violation by the Company of the Securities Act, the Exchange Act, any state
securities law or any rule or regulation promulgated under the Securities Act,
the Exchange Act or any state securities law in connection with the offering
covered by the Registration Statement; PROVIDED, HOWEVER, that the Company will
not be liable for indemnification in any such case to the extent that any
losses, claims, damages or liabilities arise out of or are based upon any untrue
statement or alleged untrue statement of a material fact or omission or alleged
omission of a material fact so made in reliance upon and in conformity with
information furnished to the Company by or on behalf of Investor. The Company
will pay to Investor, partner, officer, director or controlling person any legal
or other expenses reasonably incurred by them in connection with investigating
or defending any such loss, claim, damage, liability or action if it is finally
judicially determined (which determination is not subject to appeal) that there
was such a violation.

                           (b) INDEMNIFICATION BY INVESTOR. To the extent
permitted by law, Investor will, if Registrable Securities held by Investor are
included in the securities as to which such registration, qualification or
compliance is being effected, indemnify and hold harmless the Company, each of
its directors, its officers, agents and each person, if any, who controls the
Company within the meaning of the Securities Act or the Exchange Act against any
losses, claims, damages or liabilities (joint or several) to which the Company
or any such director, officer, agent or controlling person may become subject
under the Securities Act, the Exchange Act or other federal or state law,
insofar as such losses, claims, damages or liabilities (or actions in respect
thereto) arise out of or are based upon any Violation, in each case to the
extent (and only to the extent) that such Violation occurs in reliance upon and
in conformity with written information furnished by or on behalf of Investor
under an instrument executed by Investor and stated to be specifically for use
in connection with such registration; and Investor will pay as incurred any
legal or other expenses reasonably incurred by the Company or any such director,
officer, agent, controlling person or other person in connection with
investigating or defending any such loss, claim, damage, liability or action if
it is finally judicially determined (which determination is not subject to
appeal) that there was such a Violation; PROVIDED, HOWEVER, that in no event
shall any indemnity under this Section 2.5(b) exceed the dollar amount of
proceeds from the offering received by Investor.

                           (c) CONDUCT OF INDEMNIFICATION PROCEEDINGS. Promptly
after receipt by an indemnified party under this Section 2.5 of notice of the
commencement of any action (including any governmental action), such indemnified
party will, if a claim in respect thereof is to be made against any indemnifying
party under this Section 2.5, deliver to the indemnifying party a written notice
of the commencement thereof and the indemnifying party shall have the right to
participate in, and, to the extent the indemnifying party so desires, jointly
with any other indemnifying party similarly noticed, to assume the defense
thereof with counsel mutually satisfactory to the parties; PROVIDED, HOWEVER,
that an indemnified party shall have the right to retain its own counsel, with
the fees and expenses to be paid by the indemnifying party, if, in the
reasonable judgment of such indemnified party, based upon advice of counsel, a
conflict of interest may exist between such indemnified party and the
indemnifying party with respect to such claims (in which case, if the
indemnified party notifies the indemnifying party in writing that it elects to
employ separate counsel at the expense of the indemnifying party, the
indemnifying party shall not have the right to assume


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the defense of such claim on behalf of such indemnified party; PROVIDED,
HOWEVER, that the indemnified party shall be entitled to select only one counsel
at the expense of the indemnifying party and such counsel shall be reasonably
acceptable to the indemnifying party). The failure to deliver written notice to
the indemnifying party within a reasonable time of the commencement of any such
action, if it is finally determined in a court of competent jurisdiction (which
determination is not subject to appeal) that such failure is materially
prejudicial to its ability to defend such action, shall relieve such
indemnifying party of any liability to the indemnified party under this Section
2.5, but the omission so to deliver written notice to the indemnifying party
will not relieve it of any liability that it may have to any indemnified party
otherwise than under this Section 2.5. No indemnifying party shall be liable for
any settlement of any claim or action effected without its written consent.

                           (d) CONTRIBUTION. If the indemnification provided for
in this Section 2.5 is held by a court of competent jurisdiction to be
unavailable to an indemnified party with respect to any losses, claims, damages
or liabilities referred to herein, the indemnifying party, in lieu of
indemnifying such indemnified party thereunder, shall to the extent permitted by
applicable law contribute to the amount paid or payable by such indemnified
party as a result of such loss, claim, damage or liability in such proportion as
is appropriate to reflect the relative fault of the indemnifying party on the
one hand and of the indemnified party on the other in connection with the
Violation(s) that resulted in such loss, claim, damage or liability, as well as
any other relevant equitable considerations. The relative fault of the
indemnifying party and of the indemnified party shall be determined by a court
of law by reference to, among other things, whether the untrue or alleged untrue
statement of a material fact or the omission to state a material fact relates to
information supplied by the indemnifying party or by the indemnified party and
the parties' relative intent, knowledge, access to information and opportunity
to correct or prevent such statement or omission; PROVIDED, that in no event
shall any contribution by Investor hereunder exceed the dollar amount of
proceeds from the offering received by Investor.

                           (e) SURVIVAL; SETTLEMENT. The obligations of the
Company and Investor under this Section 2.5 shall survive completion of any
offering of Registrable Securities in a registration statement and the
termination of this Registration Rights Agreement. No indemnifying party, in the
defense of any such claim or litigation, shall, except with the consent of each
indemnified party, consent to entry of any judgment or enter into any settlement
which does not include as an unconditional term thereof the giving by the
claimant or plaintiff to such indemnified party of a release from all liability
in respect to such claim or litigation.

         3. RULE 144. The Company covenants that it will file the reports
require to be filed by it (if so required) under the Securities Act and the
Exchange Act and the Rules and Regulations adopted by the SEC thereunder in a
timely manner and, if at any time the Company is not required to file such
reports, it will, upon the request of Investor, make publicly available other
information so long as necessary to permit sales pursuant to Rule 144 under the
Securities Act. The Company further covenants that it will take such further
action as Investor may reasonably request, all to the extent required from time
to time to enable Investor to sell Registrable Securities without registration
under the Securities Act pursuant to the exemptions provided by Rule 144 under
the Securities Act. Upon the request of Investor, the Company will deliver to
Investor a written statement as to whether it has complied with such information
requirements.

         4.       MISCELLANEOUS.

                  4.1 GOVERNING LAW. This  Registration  Rights Agreement shall
be governed by and construed under the laws of the State of Delaware.


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                  4.2 SURVIVAL. The representations, warranties, covenants, and
agreements made herein shall survive any investigation made by Investor and the
closing of the transactions contemplated hereby.

                  4.3 ENTIRE AGREEMENT. This Registration Rights Agreement,
including any exhibits hereto, the Purchase Agreement and the other documents
delivered pursuant thereto constitute the full and entire understanding and
agreement between the parties with regard to the subjects hereof and no party
shall be liable or bound to any other in any manner by any representations,
warranties, covenants and agreements except as specifically set forth herein and
therein.

                  4.4 SEVERABILITY. In case any provision of the Agreement shall
be invalid, illegal, or unenforceable, the validity, legality, and
enforceability of the remaining provisions shall not in any way be affected or
impaired thereby.

                  4.5 AMENDMENT AND WAIVER. The provisions of this Registration
Rights Agreement, including the provisions of this sentence, may not be amended,
modified or supplemented, and waivers or consents to departures from the
provisions hereof may not be given, unless the Company has obtained the written
consent of Investor.

                  4.6 DELAYS OR OMISSIONS. It is agreed that no delay or
omission to exercise any right, power or remedy accruing to Investor, upon any
breach, default or noncompliance of the Company under this Registration Rights
Agreement shall impair any such right, power or remedy, nor shall it be
construed to be a waiver of any such breach, default or noncompliance, or any
acquiescence therein, or of any similar breach, default or noncompliance
thereafter occurring. It is further agreed that any waiver, permit, consent or
approval of any kind or character on Investor's part of any breach, default or
noncompliance under the Agreement or any waiver on Investor's part of any
provisions or conditions of this Registration Rights Agreement must be in
writing and shall be effective only to the extent specifically set forth in such
writing. All remedies, either under this Registration Rights Agreement, by law,
or otherwise afforded to Investor, shall be cumulative and not alternative.

                  4.7 NOTICES. All notices, requests, consents and other
communications hereunder shall be in writing and shall be deemed effectively
given: (a) upon personal delivery to the party to be notified, (b) when sent by
confirmed facsimile if sent during normal business hours of the recipient; if
not, then on the next business day, (c) upon receipt when sent by first-class
registered or certified mail, return receipt requested, postage prepaid, or (d)
upon receipt after deposit with a nationally recognized overnight express
courier, postage prepaid, specifying next day delivery with written verification
of receipt. All communications shall be sent to the party to be notified at the
address as set forth below or at such other address as such party may designate
by ten (10) days advance written notice to the Company. All communications shall
be addressed as follows:


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                           (a)      if to the Company, to:

                                    Dr. Joseph Rubinfeld
                                    President & CEO
                                    SuperGen, Inc.
                                    Two Annabel Lane
                                    San Ramon,  CA   94583
                                    Telephone: 925-327-0200
                                    Facsimile: 925-327-7347

                                    and to:

                                    John Roos, Esq.
                                    Wilson Sonsini Goodrich & Rosati,
                                    Professional Corporation
                                    650 Page Mill Road
                                    Palo Alto,  CA  94304-1050
                                    Telephone: 650-493-9300
                                    Facsimile: 650-493-6811


                           (b)      if to the Investor, at the address as set
                                    forth on the Execution Page of this
                                    Registration Rights Agreement.

                  4.8 ATTORNEYS' FEES. In the event that any dispute among the
parties to this Registration Rights Agreement should result in litigation, the
prevailing party in such dispute shall be entitled to recover from the losing
party all fees, costs and expenses of enforcing any right of such prevailing
party under or with respect to this Registration Rights Agreement, including
without limitation, such reasonable fees and expenses of attorneys and
accountants, which shall include, without limitation, all fees, costs and
expenses of appeals.

                  4.9 TITLES AND SUBTITLES. The titles of the sections and
subsections of this Registration Rights Agreement are for convenience of
reference only and are not to be considered in construing this Registration
Rights Agreement.

                  4.10 COUNTERPARTS. This Registration Rights Agreement may be
executed in any number of counterparts, each of which shall be an original, but
all of which together shall constitute one instrument.



                                      SUPERGEN, INC.
                                      A Delaware corporation



                                      By: /s/ Joseph Rubinfeld
                                          --------------------
                                      Name: Joseph Rubinfeld, Ph.D.
                                            -----------------------
                                      Title: President & Chief Executive Officer
                                             -----------------------------------


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                  By signing below, the undersigned agrees to the terms of the
SUPRGEN, INC. Registration Rights Agreement.




                   INVESTOR:




                   By: /s/ Alan P. Timmins
                       -------------------
                   Name: Alan P. Timmins

                   Title: Chief Operating Officer & Chief Financial Officer

                   Address: One SW Columbia, Suite 1105 Portland, OR 97258

                   Facsimile: (503) 227-0751


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