Board of Patent Appeals and Interferences
Patent and Trademark Office (P.T.O.)
*1 COLBERT ET AL.
LOFDAHL ET AL.
Patent Interference No. 101,755
August 30, 1991
Final Hearing January 30, 1990
Cloned Genes Encoding Recombinant Protein A
Application of Donald A. Colbert and Algis Anilionis, Serial No. 436,955, filed October 27, 1982.
Application of Sven Lofdahl, Mathias Uhlen and Martin Lindberg, Serial No. 601,630, filed April 10, 1984. Accorded benefit of Swedish application No. 8204810-9 filed August 23, 1982 and PCT/SE83/00297 filed August 23, 1983.
Fred C. Philpitt, Lawrence E. Laubscher, Lawrence E. Laubscher, Jr., and Robert L. Price for Lofdahl et al. Oral argument by Robert L. Price.
Before Caroff, Downey and Metz
This interference involves an application to Colbert et al, assigned to Replegen Corporation and an application of Lofdahl et al assigned to Pharmacia AB.
The subject matter of the interference relates to a certain recombinant DNA molecule and is defined by the following count:
Count 2 [FN1]
A recombinant DNA molecule constructed by in vitro methods and comprising a nucleotide sequence encoding the amino acid sequence of a product selected from the group consisting of protein A, a polypeptide fragment thereof, and a mixture of polypeptide fragments thereof, each of said products having protein A activity.
The claims of the parties which correspond to the count are:
Colbert et al: claims 1-34
Lofdahl et al: claims 23-42
Lofdahl et al (Lofdahl) was accorded benefit of the filing date, August 23, 1982, of their Swedish patent application No. 8204810-9 in the declaration notice. Accordingly, Lofdahl is senior party.
In accordance with a statement of facts agreed to by the parties under 37 CFR § 1.672(f) dated April 17, 1989, junior party Colbert et al (Colbert) conceived and reduced to practice in the United States the invention defined by the count at least as early as June 25, 1982; Colbert exercised reasonable diligence in reducing to practice the invention defined by the count and that following reduction to practice Colbert did not abandon, suppress or conceal the invention defined by the count. Both parties also agreed that Lofdahl conceived and reduced the invention to practice in Sweden at least prior to September 3, 1981, including the production of a clone having protein A activity and produced by recombinant DNA technique; that Lofdahl entered the U.S., on September 3, 1981, bringing with him from Sweden bacteria plates capable of containing a gene library; that Lofdahl tested some biological material in the U.S. in December, 1981, using a technique provided to him by Thomas Meyer, and conveyed the results to Thomas Meyer.
The issue presented for our determination is whether Lofdahl has established introduction of the invention into the United States prior to June 25, 1982, in accordance with the applicable legal standards. More specifically, the issues presented for our consideration are 1) whether the initial draft of a letter written by Lofdahl and intended for Dr. Novick at Public Health Research Institute (PHRI) in New York City constitutes a conception of the invention and 2) whether Lofdahl's act of bringing bacteria plates containing a gene library of 504 clones including a clone numbered 220 identified as having protein A activity, produced in Sweden, to the U.S. on September 3, 1981 and placing the same in the refrigerator at PHRI constitutes conception and reduction to practice of the invention in the U.S.
*2 Both parties presented briefs and appeared at final hearing through counsel.
The Case for Lofdahl
The Lofdahl record consists of a number of declarations (13) and exhibits (1- 19). [FN2]
Lofdahl stated that in the spring of 1981, he wrote to Dr. Novick at the PHRI regarding his forthcoming work at the Institute. The initial draft of this letter is submitted as Ex. 5. Lofdahl alleged that this draft (at the bottom of page 1) refers to work on a gene library from S. Aureus in E. Coli which was under preparation in Sweden and at the bottom of page 2, he noted that "to that point the experiments had been unsuccessful in a homologous system, but that I was convinced that it would be better to use a heterologous system, (i.e., to clone with E. coli as host), and that I intended to look for protein A production from the clones." (R-24).
Sven Lofdahl, Mathias Uhlen and Martin Lindberg, coinventors of the subject matter of the involved application, worked in laboratories of Uppsala University, Uppsala, Sweden. The coinventors stated in their declaration that a gene library comprising 504 clones was made by obtaining 8-10 kilobase chromosomal DNA fragments from Staphylococcus aureus, inserting these DNA fragments into vector pBR 322 and transforming the hybrid vector into Escherichia coli. (R-9-14). Lab technician Hans Peterrsson, an employee of coinventor Lindberg, testified that he was responsible for culturing and numbering the gene library containing the 504 clones and replicating the gene library into at least two sets of 21LA plates. By August 11, 1981, Professor Hans Wigzell of Uppsala University, tested the 504 clones for protein A activity using the ELISA technique and found that clone No. 220 tested positive for protein A activity (R-41-42; Ex. 2, 2A and 3). Bengt Guss testified that sometime after September of 1981 while in the employ of Lindberg and Uhlen, he continued to work on characterizing and analyzing the protein A active clone with regard to gene structure by employing restriction enzyme analysis. (R-29- 31). All of the above work was done in Sweden.
Lindberg testified that the gene library was replicated in order to provide Lofdahl with a fresh complete copy of the gene library prior to his departure to the U.S. on September 3, 1981. (R-39). Lofdahl testified that he personally handcarried bacteria plates containing the gene library into the U.S. on September 3, 1981. Lofdahl offers the testimony of his wife, Gunilla, to corroborate transporting of the bacteria plates to the U.S and the testimony of Saleem Khan (Khan), Alexandra Gruss (Gruss), Hakan Gadler (Gadler) and Thomas Meyer (Meyer), coworkers at PHRI, as corroboration of the invention in this country. Specifically, Gunilla Lofdahl stated that she packed bacteria plates wrapped in Parafilm having a characteristic odor into her husband's luggage; that she was aware that these plates formed a "gene bank" produced by her husband and collaborators at the University; and that it contained genetically manipulated bacteria capable of producing a substance called protein A. Gruss and Khan testified that they learned from Lofdahl through conversations with him that Lofdahl had a staphylococcal gene library and that he was working a protein A project. (R-44, 45, and 47). Similarly, Gadler testified that he learned from conversing with Lofdahl that Lofdahl brought a gene library, produced in Sweden, to the U.S. and that the library contained a recombinant clone which had protein A activity which would be useful (R-49). Likewise, Meyer testified that through conversations with Lofdahl he learned from Lofdahl that he kept in his laboratory at PHRI a recombinant E. Coli clone having protein A activity, i.e., containing a functional staphylococcal protein A gene. In addition, Meyer testified that he introduced Lofdahl to an assay technique for testing for protein A activity which employs radioactive-labelled IgG and detects protein A activity radiographically and that he provided Lofdahl with the necessary radioactive-labelled IgG. (R-52-53). Lofdahl averred that in December 1981, he tested the protein A active E. Coli clone No. 220 in the U.S. using the technique taught to him by Meyer and then showed Meyer the autoradiographs obtained together with the corresponding agar plates with live colonies. (R-55-56).
*3 From this record and exhibits, Lofdahl concludes that he has established 1) conception of the invention in the United States as evidenced by the initial draft of a letter intended for Dr. Novick (Exhibit 5) and 2) conception and reduction to practice of the invention on September 3, 1981 when Lofdahl came to the United States and brought with him bacteria plates containing a gene library of 504 clones which included clone No. 220 having an active protein A material produced in Sweden, which Lofdahl alleges conforms to all the limitations of the count, and placed the plates in a refrigerator at the PHRI in New York City.
Preliminarily, we note that Colbert points out that the Lofdahl record alleges oral conception of the invention in the United States on or about April 20, 1981 by Sven Lofdahl to Richard Novick and others at the Public Health Research Institute in New York. R-8. However, the Lofdahl position with regard to this activity for conception is not set forth in the brief. Matters not raised in the brief are ordinarily regarded as abandoned. Photis v. Lunkenheimer, 225 USPQ 948 (Bd.Pat.Int.1984).
We hold that Lofdahl has failed to establish conception and reduction to practice of the subject matter of the count in issue in the United States prior to June 25, 1982, the date of conception and reduction to practice given to Colbert et al.
Specifically, we find Exhibit 5 of no probative value to establish introduction of the invention into the U.S. since it does not establish the existence of any letter received in the U.S. which supports a finding of conception of the subject matter of the count in issue. Exhibit 5 in our view evinces, at best, only an intent to write to Dr. Novick. [FN3]
Nor do we find that Lofdahl's act of bringing bacteria plates into the U.S. and placing the same in a refrigerator at the PHRI constitute simultaneous conception and reduction to practice in the U.S. of the subject matter of the count in issue as alleged by Lofdahl. In the instant case, we find that Lofdahl has not sustained his burden of establishing by a preponderance of evidence that a compound within the scope of the count, i.e., a DNA recombinant molecule comprising a nucleotide sequence encoding for protein A or a fragment of protein A, was introduced into this country before June 25, 1982. Our reasons follow.
In the case of conception and reduction to practice, it is well settled that the conception must take place in the United States, or in lieu thereof, it must have been brought to this country or must have been communicated to someone in this country. Wilson v. Sherts, 81 F.2d 755, 28 USPQ 379 (CCPA 1936). If the invention is reduced to practice in a foreign country and knowledge of the invention was brought into this country and disclosed to others, the inventor can derive no benefit from the work done abroad and such knowledge is merely evidence of conception of the invention. DeKando v. Armstrong, 169 O.G. 1185, 1911 CD 413 (App.D.C.1911); see also 35 USC 104. [FN4] However, the nature of the work abroad might be important in determining the identity of the invention or whether the inventor had any concept of it or not, but it is incumbent upon the inventor to prove that the invention was introduced into the United States. Breuer v. DeMarinis, 558 F.2d 22, 194 USPQ 308 (CCPA 1977); and Rebuffat v. Crawford, 68 F.2d 980, 982, 20 USPQ 321, 324 (CCPA 1934). Introduction of the invention into this country on behalf of the inventors must be judged by what knowledge was imparted to others and by the items brought into the U.S. by Lofdahl. Micheletti v. Tapia, 196 USPQ 858 (Bd.Pat.Int.1976).
*4 Conception is the "formation in the mind of the inventor, of a definite and permanent idea of the complete and operative invention, as it is hereafter to be applied in practice. Hybritech, Inc. v. Monclonal Antibodies, Inc., 802 F.2d 1367, 1376, 231 USPQ 281, 87 (Fed.Cir.1988), cert. denied, 480 U.S. 947 (1987). For a compound, conception requires both the idea of the invention's structure and possession of an operative method of making it. Oka v. Youssefyeh, 849 F.2d 581, 583, 7 USPQ2d 1169, 1171 (Fed.Cir.1988).
The invention recited in the count at issue is directed to a recombinant DNA molecule, a complex chemical compound, comprising a nucleotide sequence encoding the amino acid sequence for protein A or a fragment thereof. Conception of a chemical compound requires that the inventor be able to define it so as to distinguish it from other materials, and to describe how to obtain it. Amgen, Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016, 1020, 1021 (Fed.Cir.1991) citing Oka, 849 F.2d at 583, 7 USPQ2d at 1171. When an inventor is unable to envision the detailed constitution of a gene so as to distinguish it from other materials, as well as a method for obtaining it, conception has not been achieved until reduction to practice has occurred, i.e., until after the gene has been isolated. Amgen, Inc. v. Chugai Pharmaceutical Co. Ltd., supra.
We find no evidence in this record that Lofdahl had possession of the chemical structure of the complex chemical compound of the count, i.e., that the DNA molecule had been isolated and its nucleotide sequence known, before June 25, 1982 and that knowledge of the chemical structure and method of making it was communicated to someone in the U.S. Simply recognizing that it tests positive in an assay does not provide sufficient chemical structure or sufficient characteristics of the recombinant molecule such that one of ordinary skill in the art would be able to distinguish it from other materials. Amgen, Inc. v. Chugai Pharmaceutical Co., Ltd., supra. It is not sufficient to define the recombinant molecule by its principal biological property, e.g., having protein A activity, because an alleged conception having no more specificity than that is simply a wish to know the identity of any material with that biological property. Amgen, Inc. v. Chugai Pharmaceutical Co., Ltd., supra.
Lofdahl maintains that it was sufficient that he himself brought the plates to the U.S. and that he knew the identity of the gene material, how to produce the active gene, and knew the utility of the active gene. On the contrary, it is insufficient that the invention was brought to this country by the inventor himself. The inventor must make an adequate disclosure of the invention to some one in this country. Conception of an invention must have been manifested or proved by means of exterior acts or declarations (disclosures). I Rivise & Caesar, Interference Law and Practice, § 116, (p. 338) (Michie Co.1943). Herein, the bacteria plates were not accompanied by any documentation which would adequately show importation, identification and method of preparation of the complex chemical compound of the count. Cf. Breuer v. Demarinis, supra (where a transmission record included the infrared spectrum of the transmitted compound and clearly disclosed the synthesis and chemical structure of the compound within count). Moreover, Lofdahl has provided no objective evidence that establishes with certainty that he knew the "identity" of the gene material, i.e., the nucleotide sequence of protein A, as required by the count and that such knowledge was communicated to others in the U.S. While Lofdahl knew of a means of producing a staphylococcal gene library and knew that clone 220 produced a positive result when subjected to an ELISA technique, until the clone was isolated and its sequence known, there was no certainty that clone 220 encoded the amino acid sequence for protein A.
*5 The testimony of Lofdahl's wife, Gunilla, and coworkers Khan, Gadler, Meyer and Guss to corroborate the introduction of the invention into this country is ineffective since the Lofdahl record has not established conception and reduction to practice of the invention of the count in this country. Moreover, their statements which originated from the inventor himself cannot constitute independent corroboration of the inventor's acts. Larson v. Johenning, 17 USPQ2d 1610 (BPAI 1990); Reese v. Hurst, 661 F.2d 1222, 211 USPQ 936, 940 (CCPA 1981).
For the foregoing reasons, judgment as to the subject matter of count 2 is awarded to Donald A. Colbert and Algis Anilionis, the junior party. Sven Lofdahl, Mathias Uhlen and Martin Lindberg are not entitled to claims 23 through 42 which correspond to the count.
BOARD OF PATENT APPEALS AND INTERFERENCES
Marc L. Caroff
Mary F. Downey
Andrew H. Metz
FN2. The record and exhibits will be referred to below as R- and Ex-.
FN3. Dr. Novick did not testify in this proceeding.
FN4. 35 USC 104 states in part:
In proceedings in the Patent and Trademark Office and in the courts, an applicant for a patent, or a patentee, may not establish a date of invention by reference to knowledge or use thereof, or other activity with respect thereto, in a foreign country, except as provided in sections 119 and 365 of this title.