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F I N N EG AN 
HENDERSON 
FARABOW 
GARRETT & 
DUNNERLif 

1 300 I Street, NW 
Washington, DC 20005 
202.408.4000 
Fax 202.408.4400 
www.finnegan.com 



PATENT 
Customer No. 22,852 
Attorney Docket No. 08702.0039-02000 

AMENDMENTS TO THE SPECIFICATION: 

Please amend the specification as follows: 

Please delete the paragraphs added to the beginning of the specification by 
preliminary amendment on March 9, 2001. Please replace the paragraph beginning at 
page 1 , line 1 , of the specification as filed, with the following amended paragraph: 

This application is a continuation of USSN 08/925.779. filed September 9. 1 997 
(U.S. Patent No. 6.245.889). which is a continuation of USSN 07/721,847. filed June 14. 
1991 (U.S. Patent No. 6.150.328). which is a continuation-in-part of U.S. Serial Nos. 
07/493,272, filed March 14, 1990 (abandoned) (which is a CIP of 07/406,217, filed 
September 12, 1989 (abandoned)) : 378,537 filed July 11, 1989; and 655,579, filed 
February 14, 1991 (U.S. Patent No. 5.618.924). which is a divisional of 07/179,100, filed 
April 8, 1988 (now U.S. Patent No. 5,013,649) which is a continuation-in-part of 
07/028,280, filed March 20, 1987 now abandoned; 943,532, filed December 17, 1986 
now abandoned;-and 880,776rfiled-July-1— 1986 now-abandonedr 



Please replace the paragraph beginning at page 23, line 19, with the following 
amended paragraph: 

Full length human BMP-2 cDNA clones are obtained in the following manner. 
The 1 .5 kb insert of one of the BMP-4 subclones (11-10-1) is isolated and radioactively 
labeled by nick-translation. One set of the nitrocellulose replicas of the U-2 OS cDNA 
library screened above (50 filters, corresponding to 1 ,000,000 recombinant 
bacteriophage) are rehybridized with this probe under stringent conditions (hybridization 
at 65° in 0.2 X SSC, 0.1% SDS). All recombinants which hybridize to the bone genomic 
probe which do not hybridize to the BMP-4 probe are picked and plaque purified (10 

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F I N N EG AN 
HENDERSON 
FARABOW 
GARRETT & 
DUNNER l _lp 

1300 I Street, NW 
Washington, DC 20005 
202.408.4000 
Fax 202.408.4400 
www.finnegan.com 



PATENT 
Customer No. 22,852 
Attorney Docket No. 08702.0039-02000 

recombinants). Plate stocks are made and small scale bacteriophage DNA 

preparations made. After subcloning into M13, sequence analysis indicates that 4 of 

these represent clones which overlap the original BMP-2 clone. One Two of these, 

lambda U20S-39 and U2QS-3 . was were deposited with the ATCC (10801 University 

Boulevard. Manassas. VA. 201 10-2209). under the Budapest Treaty, on June 16, 1987 

under accession number 40345 and 40342. respectively . The DNA sequence (SEQ ID 

NO: 3) (compiled from lambda U20S-39 and several other hBMP-2 cDNA 

recombinants) and derived amino acid sequence (SEQ ID NO: 4) are shown below in 

Figure 2. Lambda U20S-39 is expected to contain all the nucleotide sequence 

necessary to encode the entire human counterpart of the protein BMP-2 encoded by the 

bovine gene segment whose partial sequence is presented in Figure 1 . The BMP-2 

protein encoded by the DNA sequence of Figure 2 is contemplated to contain the 97 

amino acid sequence from amino acid #299 to #396 or a sequence substantially 



homologous thereto. This~human cDNA~hBMP-2 contains an open reading-frame of 

1 188 bp, encoding a protein of 396 amino acids. The protein is preceded by a 5' 
untranslated region of 342 bp with stop codons in all frames. The 13 bp region 
preceding this 5' untranslated region represents a linker used in the cDNA cloning 
procedure. This protein of 396 amino acids has a molecular weight of 45kd based on 
this amino acid sequence. It is contemplated that this sequence represents the primary 
translation product. It is further contemplated that BMP-2 may correspond to the 
approximately 18 - 20 kd subunit of Example IIC. The sequence corresponding to the 
sequence tryptic Fragment 3 of Example IV is underlined in Figure 2. The "pre" portion 
of the human BMP-2 protein is contemplated to comprise amino acid #1 to amino acid 



PATENT 
Customer No. 22,852 
Attorney Docket No. 08702.0039-02000 

#23 as shown in Figure 2. The "pro" portion is contemplated to comprise amino acid 

#24 to amino acid #282 of Figure 2 (SEQ ID NO: 4). The mature portion is 

contemplated to comprise amino acid #283 (Gin, Ala, Lys...) to #396 (Arg) of Figure 2. 



FINNECAN 
HENDERSON 
FARABOW 
GARRETT & 
DUNNERLLf 

1300 I Street, NW 
Washington, DC 20005 
202.408.4000 
Fax 202.408.4400 
www.fi nnegan .com 



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