<PAGE>   1





                       SECURITIES AND EXCHANGE COMMISSION
                             Washington, D.C. 20549

                                  ---------

                                  FORM 10-K/A
                                Amendment No. 2

                 ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d)
                     OF THE SECURITIES EXCHANGE ACT OF 1934

                                  ---------

For the fiscal year ended December 31, 1997       Commission File Number 0-22962

                          HUMAN GENOME SCIENCES, INC.
                           (Exact name of registrant)

      Delaware                                          22-3178468
(State of organization)                  (I.R.S. employer identification number)

                9410 Key West Avenue, Rockville, Md. 20850-3338
             (address of principal executive offices and zip code )

                                 (301) 309-8504
                        (Registrant's telephone number)

       Securities registered pursuant to Section 12(b) of the Act:  NONE

                Securities pursuant to Section 12(g) of the Act:

                     Common stock, par value $.01 per share

Indicate by check mark whether the registrant (1) has filed all reports
required to be filed by Section 13 or 15(d) of the Securities Exchange Act of
1934 during the preceding 12 months (or for such shorter period that the
registrant was required to file such reports), and (2) has been subject to such
filing requirements for the past 90 days.  Yes X  No__

Indicate by check mark if disclosure of delinquent filers pursuant to Item 405
of regulation S-K is not contained herein, and will not be contained, to the
best of the registrant's knowledge, in definitive proxy or information
statements incorporated by reference in Part III of this Form 10-K or any
amendment to this Form 10-K. [  ]

The number of shares of the registrant's common stock outstanding on February
28, 1998 was 22,361,639.

As of February 28, 1998, the aggregate market value of the common stock held by
non-affiliates of the registrant based on the closing price reported on the
National Association of Securities Dealers Automated Quotations System was
approximately $ 576,000,000.*

                      DOCUMENTS INCORPORATED BY REFERENCE

Portions of Human Genome Sciences, Inc.'s Notice of Annual Stockholder's
Meeting and Proxy Statement, to be filed within 120 days after the end of the
registrant's fiscal year, are incorporated into Part III of this Annual Report.

*Excludes 8,805,932 shares of common stock deemed to be held by officers and
directors, and stockholders whose ownership exceeds five percent of the shares
outstanding at February 28, 1998.  Exclusion of shares held by any person
should not be construed to indicate that such person possesses the power,
direct or indirect, to direct or cause the direction of the management or
policies of the registrant, or that such person is controlled by or under
common control with the registrant.
<PAGE>   2





                                    PART IV

        The Registrant hereby amends Part IV, Item 14 of its 10-K for the
fiscal year ended December 31, 1997 to refile Exhibit 10.66, revised to include
certain previously redacted information on page 16, in response to the
Securities and Exchange Commission's comments to the Registrant's Applicantion 
for Confidential Treatment.


           



<PAGE>   3





                                    PART IV

ITEM 14.         EXHIBITS, FINANCIAL STATEMENT SCHEDULES, AND REPORTS ON FORM
                 8-K

(a)      The following documents are filed as part of this Annual Report:

(1)      Index to Financial Statements
<TABLE>
<CAPTION>
                                                                                                                  PAGE
                                                                                                                 NUMBER
                                                                                                                -------
                                        <S>                                                                       <C>
                                        Report of Ernst & Young LLP, Independent Auditors                         F-2
                                        Balance Sheets at December 31, 1997 and 1996                              F-3
                                        Statements of Operations for the years ended December 31, 1997, 1996      F-4
                                        and 1995                                                              
                                        Statements of Stockholders' Equity for the years ended December 31,
                                        1997, 1996 and 1995                                                       F-5
                                        Statements of Cash Flows for the years ended December 31, 1997, 1996      F-6
                                        and 1995  
                                        Notes to Financial Statements                                             F-7
</TABLE>

(2)      Financial Statement Schedules

         Financial statement schedules are omitted because they are not
         required.

(3)      Exhibits

<TABLE>
<CAPTION>
Exhibit No.
-----------

            <S>              <C>
             3.1*            Restated Certificate of Incorporation (Fifth) of the Registrant (Filed as Exhibit 3.1 to
                             the Registrant's Form 10-K for the fiscal year ended December 31, 1993 and incorporated
                             herein by reference).

             3.2*            By-laws of the Registrant (Filed as Exhibit 3.2 to the Registrant's Form 10-K for the
                             fiscal year ended December 31, 1993 and incorporated herein by reference).

             3.3$            Certificate of Amendment of the Certificate of Incorporation of Registrant

             4.1*            Form of Common Stock certificate.

            10.1*+           Collaboration Agreement, dated May 19, 1993, between the Registrant and SmithKline Beecham
                             Corporation ("SmithKline Beecham"), as amended on May 19, 1993 and August 19, 1993 (Filed
                             as Exhibit 10.1 to the Registrant's Form S-1 Registration Statement, as amended (Commission
                             File No. 33-69850), originally filed October 1, 1993 and incorporated herein by reference).

            10.2*            Second Amendment to HGS-SB Collaboration Agreement, effective September 1, 1993, between
                             the Registrant and SmithKline Beecham (Filed as exhibit 10.2 to the Registrant's Form 10-K
                             for the fiscal year ended December 31, 1993 and incorporated herein by reference).

            10.3*            Amendment to HGS-SB Collaboration Agreement, effective March 17, 1994, between the
                             Registrant and SmithKline Beecham (Filed as Exhibit 10.3 to the Registrant's Form 10-K for
                             the fiscal year ended December 31, 1993 and incorporated herein by reference).
</TABLE>





<PAGE>   4




<TABLE>
            <S>              <C>
            10.4*+           License Agreement between the Registrant and SmithKline Beecham Corporation dated September
                             15, 1994 (Filed as Exhibit 10.8 to the Registrant's Form 10-Q filed November 14, 1994 and
                             incorporated herein by reference).

            10.5*+           Amendment to HGS-SB Collaboration Agreement (Therapeutic Protein Amendment), effective
                             December 23, 1994, between the Registrant and SmithKline Beecham (Filed as Exhibit 10.4 to
                             the Registrant's Form 10-K for the fiscal year ended December 31, 1994 and incorporated
                             herein by reference).

            10.6*+           Amendment to HGS-SB Collaboration Agreement (Milestone III Amendment), effective December
                             29, 1994, between the Registrant and SmithKline Beecham (Filed as Exhibit 10.5 to the
                             Registrant's Form 10-K for the fiscal year ended December 31, 1994 and incorporated herein
                             by reference).

            10.7*            Amendment to the Series B Convertible Preferred Stock Purchase Agreement between the
                             Registrant and SmithKline Beecham Corporation, dated December 29, 1994.  (Filed as Exhibit
                             10.96 to the Registrant's form S-3 Registration Statement, as amended (Commission File No.
                             33-96206) originally filed August 25, 1995 and incorporated herein by reference).

            10.8*+           Amendment to HGS-SB Collaboration Agreement, effective April 24, 1995, between the
                             Registrant and SmithKline Beecham Corporation.  (Filed as Exhibit 10.6 to the Registrant's
                             form S-3 Registration Statement, as amended (Commission File No. 33-96206), originally
                             filed August 25, 1995 and incorporated herein by reference).

            10.9*+           Amendment to HGS-SB Collaboration Agreement, effective May 31, 1995, between the Registrant
                             and SmithKline Beecham. (Filed as Exhibit 10.1 to the Registrant's Form 10-Q filed August
                             14, 1995 and incorporated herein by reference).

            10.10*+          Amendment and Restated License Agreement between the Registrant and SmithKline Beecham
                             effective May 31, 1995 (Filed as Exhibit 10.1 to the Registrant's Form 10-Q filed August
                             14, 1995 and incorporated herein by reference).

            10.11*+          Amendment to SmithKline Beecham and Human Genome Sciences, Inc. Collaboration Agreement and
                             License Agreement and Amended and Restated License Agreement dated June 28, 1996. (Filed as
                             Exhibit 10.1 to the Registrants 10-Q filed August 14, 1996 and incorporated herein by
                             reference).

            10.12*+          SmithKline Beecham and Human Genome Sciences, Inc. License Agreement Dated June 28, 1996. 
                             (Filed as Exhibit 10.2 to the Registrants 10-Q filed August 14, 1996 and incorporated
                             herein by reference).

            10.13*+          Therapeutic Collaboration and License Agreement by and among Human Genome Sciences, Inc.,
                             Schering Corporation, Schering Plough Ltd., and SmithKline Beecham Corporation dated June
                             28, 1996. ( Filed as Exhibit 10.3 to the Registrants 10-Q filed August 14, 1996 and
                             incorporated herein by reference).

            10.14*+          Gene Therapy Collaboration and License Agreement by and among Human Genome Sciences, Inc.,
                             Schering Corporation, and Schering Plough Ltd., June 28, 1996. ( Filed as Exhibit 10.4 to
                             the Registrants 10-Q filed August 14, 1996 and incorporated herein reference).

            10.15*+          Collaboration and License Agreement by and among Human Genome Sciences, Inc. SmithKline
                             Beecham Corporation and Synthelabo dated June 30, 1996. ( Filed as Exhibit 10.5 to the
                             Registrants 10-Q filed August 14, 1996 and incorporated herein by reference).

            10.16*+          Collaboration and License Agreement between SmithKline Beecham Corporation, Human Genome
                             Sciences, Inc. and Merck KGaA effective July 10, 1996. ( Filed as Exhibit 10.6 to the
                             Registrants 10-Q filed November 14, 1996 and incorporated herein by reference).
</TABLE>





<PAGE>   5




<TABLE>
            <S>              <C>
            10.17*+          Research Collaboration Agreement between the Registrant and Genetic Therapy, Inc. dated
                             September 13, 1994 (Filed as Exhibit 10.7 to the Registrant's Form 10-Q filed November 14,
                             1994 and incorporated herein by reference).

            10.18*+          Option and License Agreement between the Company and Takeda Chemical Industries, Ltd. dated
                             June 12, 1995 (Filed as Exhibit 10.3 to the Registrant's Form 10-Q filed August 14, 1995
                             and incorporated herein by reference).

            10.19*+          Collaboration and License Agreement between the Registrant and MedImmune, Inc. dated July
                             27, 1995 (Filed as Exhibit 10.5 to the Registrant's Form 10-Q filed August 14, 1995 and
                             incorporated herein by reference).

            10.20*+          Research Collaboration Agreement, dated January 19, 1996, between Registrant and Pioneer
                             Hi-Bred International, Inc. ("Pioneer"). (Filed as Exhibit 10.15 to the Registrants Form
                             10-K filed March 31,1996 and incorporated herein by reference).

            10.21*+          License Agreement between Registrant and F. Hoffmann-La Roche, Ltd. ("Roche"). (Filed as
                             Exhibit 10.16 to the Registrants Form 10-K filed March 31,1996 and incorporated herein by
                             reference).

            10.22*+          Research Services Agreement, dated October 1, 1992, between the Registrant and The
                             Institute for Genomic Research ("TIGR") (Filed as Exhibit 10.4 to the Registrant's Form S-1
                             Registration Statement, as amended (Commission File No. 33-69850), originally filed October
                             1, 1993 and incorporated herein by reference).

            10.23*+          Intellectual Property Agreement, dated October 2, 1992, between the Registrant and TIGR
                             (Filed as Exhibit 10.5 to the Registrant's Form S-1 Registration Statement, as amended
                             (Commission File No. 33-69850), originally filed October 1, 1993 and incorporated herein by
                             reference).

            10.24*           Lease Funding Agreement and Assignment, dated March 2, 1993, between the Registrant and
                             TIGR (Filed as Exhibit 10.6 to the Registrant's Form S-1 Registration Statement, as amended
                             (Commission File No. 33-69850), originally filed October 1, 1993 and incorporated herein by
                             reference).

            10.25*           Letter Agreement, dated March 31, 1993, between the Registrant and TIGR (Filed as Exhibit
                             10.7 to the Registrant's Form S-1 Registration Statement, as amended (Commission File No.
                             33-69850), originally filed October 1, 1993 and incorporated herein by reference).

            10.26*+          Letter Agreement, dated April 19, 1993, between the Registrant and TIGR (Filed as Exhibit
                             10.8 to the Registrant's Form S-1 Registration Statement, as amended (Commission File No.
                             33-69850), originally filed October 1, 1993 and incorporated herein by reference).

            10.27*           Stock Purchase, Restriction and Repurchase Agreement, dated April 26, 1993, between the
                             Registrant and TIGR (Filed as Exhibit 10.47 to the Registrant's Form S-1 Registration
                             Statement, as amended (Commission File No. 33-69850), originally filed October 1, 1993 and
                             incorporated herein by reference).

            10.28*           Letter Agreement, dated May 7, 1993, between the Registrant and TIGR (Filed as Exhibit 10.9
                             to the Registrant's Form S-1 Registration Statement, as amended (Commission File No.
                             33-69850), originally filed October 1, 1993 and incorporated herein by reference).
</TABLE>





<PAGE>   6




<TABLE>
            <S>              <C>
            10.29*+          Human cDNA Database Agreement among the Registrant, SmithKline Beecham Corporation, and The
                             Institute for Genomic Research dated July 7, 1994 (Filed as Exhibit 10.5 to the
                             Registrant's Form 10-Q filed November 14, 1994 and incorporated herein by reference).

            10.30*+          Amendment to the Human cDNA Database Agreement between the Registrant and SmithKline
                             Beecham Corporation and the Institute for Genomic Research dated October 26, 1994 (Filed as
                             Exhibit 10.6 to the Registrant's Form 10-Q filed November 14, 1994 and incorporated herein
                             by reference).

            10.31*+          Second Amendment to the Human cDNA Database Agreement between the Registrant and SmithKline
                             Beecham Corporation and the Institute for Genomic Research dated as of April 14, 1995
                             (Filed as Exhibit 10.87 to the Registrant's Form 10-K for the fiscal year ended December
                             31, 1994 and incorporated herein by reference).

            10.32*           Common Stock Purchase Warrant, dated June 8, 1993, granted to HCV III (Filed as Exhibit
                             10.33 to the Registrant's Form S-1 Registration Statement, as amended (Commission File No.
                             33-69850), originally filed October 1, 1993 and incorporated herein by reference).

            10.33*           Common Stock Purchase Warrant, dated June 8, 1993, granted to HCV IV (Filed as Exhibit
                             10.34 to the Registrant's Form S-1 Registration Statement, as amended (Commission File No.
                             33-69850), originally filed October 1, 1993 and incorporated herein by reference).

            10.34*           Common Stock Purchase Warrant, dated June 8, 1993, granted to Everest (Filed as Exhibit
                             10.36 to the Registrant's Form S-1 Registration Statement, as amended (Commission File No.
                             33-69850), originally filed October 1, 1993 and incorporated herein by reference).

            10.35*           Master Lease Agreement, dated January 31, 1993, between the Registrant and MMC/GATX
                             Partnership No. I (Filed as Exhibit 10.25 to the Registrant's Form S-1 Registration
                             Statement, as amended (Commission File No. 33-69850), originally filed October 1, 1993 and
                             incorporated herein by reference).

            10.36*           Warrant Agreement, dated January 31, 1993, between the Registrant and MMC/GATX Partnership
                             No. I (Filed as Exhibit 10.26 to the Registrant's Form S-1 Registration Statement, as
                             amended (Commission File No. 33- 69850), originally filed October 1, 1993 and incorporated
                             herein by reference).

            10.37*           Master Lease Agreement, dated as of January 31, 1993, between the Registrant and Dominion
                             Ventures, Inc. (Filed as Exhibit 10.27 to the Registrant's Form S-1 Registration Statement,
                             as amended (Commission File No. 33-69850), originally filed October 1, 1993 and
                             incorporated herein by reference).

            10.38*           Master Lease Agreement, dated January 31, 1993, between the Registrant and Comdisco, Inc.
                             (Filed as Exhibit 10.29 to the Registrant's Form S-1 Registration Statement, as amended
                             (Commission File No. 33-69850), originally filed October 1, 1993 and incorporated herein by
                             reference).

            10.39*           Master Lease Agreement (Equipment) between the Registrant and Comdisco, Inc., dated June
                             30, 1994 (Filed as Exhibit 10.12 to the Registrant's Form 10-Q filed August 12, 1994 and
                             incorporated herein by reference).

            10.40*           Lease of Premises at 9620 Medical Center Drive, Rockville, Maryland (Filed as Exhibit 10.42
                             to the Registrant's Form S-1 Registration Statement, as amended (Commission File No.
                             33-69850), originally filed October 1, 1993 and incorporated herein by reference).
</TABLE>





<PAGE>   7




<TABLE>
            <S>              <C>
            10.41*           Lease of Premises at 9430 Key West Avenue, Rockville, Maryland (Filed as Exhibit 10.44 to
                             the Registrant's Form S-1 Registration Statement, as amended (Commission File No.
                             33-69850), originally filed October 1, 1993 and incorporated herein by reference).

            10.42*           Office Lease between the Registrant and Key West IV Limited Partnership, dated June 14,
                             1994 (Filed as Exhibit 10.11 to the Registrant's Form 10-Q filed August 12, 1994 and
                             incorporated herein by reference).

            10.43*           Stock Purchase and Restriction Agreement, dated December 31, 1992, between the Registrant
                             and William A. Haseltine, Ph.D. (Filed as Exhibit 10.15 to the Registrant's Form S-1
                             Registration Statement, as amended (Commission File No. 33-69850), originally filed October
                             1, 1993 and incorporated herein by reference).

            10.44*           Employment Agreement, dated February 25, 1997, with William A. Haseltine, Ph.D. (Filed as
                             Exhibit 10.44 to the Registrant's Form 10 K for the fiscal year ended December 31, 1996 and
                             incorporated herein by reference).

            10.45*           Restricted Stock Purchase Agreement, dated May 18, 1993, between the Registrant and William
                             A. Haseltine, Ph.D. (Filed as Exhibit 10.24 to the Registrant's Form S-1 Registration
                             Statement, as amended (Commission File No. 33-69850), originally filed October 1, 1993 and
                             incorporated herein by reference).

            10.46*           Promissory Note, dated March 4, 1994, given by William A. Haseltine, Ph.D. to the
                             Registrant (Filed as Exhibit 10.58 to the Registrant's Form 10-K for the fiscal year ended
                             December 31, 1993 and incorporated herein by reference).

            10.47*           First Allonge to Promissory Note, dated December 16, 1994, given by William A. Haseltine,
                             Ph.D. to the Registrant (Filed as Exhibit 10.65 to the Registrant's Form 10-K for the
                             fiscal year ended December 31, 1994 and incorporated herein by reference).

            10.48*           Pledge Agreement, dated March 4, 1994, between William A. Haseltine, Ph.D. and Registrant
                             (Filed as Exhibit 10.59 to the Registrant's Form 10-K for the fiscal year ended December
                             31, 1993 and incorporated herein by reference).

            10.49*           First Amendment to Pledge Agreement, dated December 16, 1994, between William A. Haseltine,
                             Ph.D. and Registrant (Filed as Exhibit 10.67 to the Registrant's Form 10-K for the fiscal
                             year ended December 31, 1994 and incorporated herein by reference).

            10.50*           Employment Agreement, dated October 1992, with Craig A. Rosen, Ph.D. (Filed as Exhibit
                             10.17 to the Registrant's Form S-1 Registration Statement, as amended (Commission File No.
                             33-69850), originally filed October 1, 1993 and incorporated herein by reference).

            10.51*           Restricted Stock Purchase Agreement, dated April 21, 1993, between the Registrant and Craig
                             A. Rosen, Ph.D. (Filed as Exhibit 10.22 to the Registrant's Form S-1 Registration
                             Statement, as amended (Commission File No. 33-69850), originally filed October 1, 1993 and
                             incorporated herein by reference).

            10.52*           Employment Agreement, dated March 14, 1994, with Bradley G. Lorimier (Filed as Exhibit
                             10.22 to the Registrant's Form 10-K for the Fiscal year ended December 31, 1993 and
                             incorporated herein by reference).
</TABLE>





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<TABLE>
            <S>              <C>
            10.53*           Promissory Note dated September 12, 1994, given by Bradley G. Lorimier to the Registrant
                             (Filed as Exhibit 10.9 to the Registrant's Form 10-Q filed November 14, 1994 and
                             incorporated herein by reference).

            10.54*           Employment Agreement, dated January 23, 1995 with Robert H. Benson (Filed as Exhibit 10.27
                             to the Registrant's From 10-K for the Fiscal year ended December 31, 1994 and incorporated
                             herein by reference).

            10.55*           Employment Agreement between the Company and Melvin D. Booth dated June 19, 1995 (Filed as
                             Exhibit 10.4 to the Registrant's Form 10-Q filed August 14, 1995 and incorporated herein by
                             reference).

            10.56*           Restricted Stock Purchase Agreement, dated April 21, 1993, between the Registrant and
                             Catherine G. Blair (Filed as Exhibit 10.19 to the Registrant's Form S-1 Registration
                             Statement, as amended (Commission File No. 33-69850), originally filed October 1, 1993 and
                             incorporated herein by reference).

            10.57*           Restricted Stock Purchase Agreement, dated April 21, 1993, between the Registrant and James
                             W. Church (Filed as Exhibit 10.20 to the Registrant's Form S-1 Registration Statement, as
                             amended (Commission File No. 33-69850), originally filed October 1, 1993 and incorporated
                             herein by reference).

            10.58*           Restricted Stock Purchase Agreement, dated April 21, 1993, between the Registrant and
                             Donald D. Johnston (Filed as Exhibit 10.21 to the Registrant's Form S-1 Registration
                             Statement, as amended (Commission File No. 33-69850), originally filed October 1, 1993 and
                             incorporated herein by reference).

            10.59*           1993 Stock Option Plan (Filed as Exhibit 10.45 to the Registrant's Form S-1 Registration
                             Statement, as amended (Commission File No. 33- 69850), originally filed October 1, 1993 and
                             incorporated herein by reference).

            10.60*           1994 Stock Option Plan (Filed as Exhibit 4 to the Registrant's Registration Statement on
                             Form S-8, File No. 33-79020, filed May 17, 1994 and incorporated herein by reference).

            10.61*           Form of Stock Option Agreement (Filed as Exhibit 10.46 to the Registrant's Form S-1
                             Registration Statement, as amended (Commission File No. 33-69850), originally filed October
                             1, 1993 and incorporated herein by reference).

            10.62*+          Agreements between the Registrant and Perkin-Elmer Corporation (Filed as Exhibit 10.48 to
                             the Registrant's Form S-1 Registration Statement, as amended (Commission File No.
                             33-69850), originally filed October 1, 1993 and incorporated herein by reference).

            10.63*           $4,000,000 Maryland Industrial Development Financing Authority Taxable Variable Rate Demand
                             Economic Development Revenue Bonds dated December 21, 1994 (Filed as Exhibit 10.90 to the
                             Registrant's Form 10-K for the fiscal year ended December 31, 1994 and incorporated herein
                             by reference).

            10.64*+          HGS/TIGR Agreement dated June 20, 1997 (Filed as Exhibit 10.1 to the Registrant's Form 10-Q
                             filed August 14, 1997 and incorporated herein by reference).

            10.65*+          Amendment to SmithKline Beecham Corporation and SmithKline Beecham p.l.c. and Human Genome
                             Sciences, Inc. Collaboration Agreement dated July 24, 1997 (Filed as Exhibit 10.2 to the
                             Registrant's 10-Q filed August 14, 1997 and incorporated herein by reference).
</TABLE>





<PAGE>   9




<TABLE>
            <S>              <C>
            10.66++#         Gene Therapy Collaboration and License Agreement between Human Genome Sciences, Inc. and
                             Transgene S.A., dated February 25, 1998.

            10.67$           Lease Agreement between Maryland Economic Development Corporation and Human Genome
                             Sciences, Inc., dated December 1, 1997.

            23.1$            Consents of Ernst & Young LLP, Independent Auditors.

            27$              Financial Data Schedule.
</TABLE>

#        Filed herewith.

*        Incorporated by reference.

$        Previously filed.

+        Confidentiality treatment has been granted by the Commission.  The
         copy filed as an exhibit omits the information subject to the
         confidentiality request.

++       Confidentiality treatment has been requested.  The copy filed as an
         exhibit omits the information subject to the confidentiality request.