In Re Gleave, 560 F3d 1331 (Fed. Cir. 2009)
SUMMARY
Composition claims for a an antisense oligodeoxynucleotide that could bind to messenger RNA for two different types of human Insulin-Dependent Growth Factor Binding Protein because of its complementary structure to the genes for these binding proteins were rejected by the patent examiner. The reasons given for rejection were indefiniteness under 35 U.S.C. § 112, anticipation under § 102 and obviousness under § 103. The examiner found the claims invalid based on prior art that provided a long list of sense oligonucleotides and disclosed general concepts that described the claimed compounds.
On appeal, the Board of Patent Appeals and Interferences reversed the rejection for indefiniteness, but affirmed rejection for anticipation and obviousness, finding that the prior art described the claimed compounds. On appeal the Federal Circuit affirmed that the claimed compounds were described adequately in prior art to be synthesized by an ordinary person skilled in the art and were, therefore, anticipated. A decision regarding obviousness was not reached.
PROCEDURAL HISTORY
The patent examiner rejected composition claims 1, 4, 15, and 18-21 of patent application No. 10/346,493 (‘493) as indefinite under 35 U.S.C. § 112, ¶ 2 and as anticipated or obvious under 35 U.S.C. § 102 (b) and § 103 (a) respectively. The United States Patent and Trademark Office Board of Patent Appeals and Interferences ("Board") reversed the rejection under Section 112 and affirmed the rejections under Sections 102 and 103. The rejections due to anticipation and obviousness were appealed.
FACTS
Antisense oligodeoxynucleotides (AODNTs) are short (typically 13-25 nucleotides), single strands of DNA that are complementary to a chosen sequence of DNA or messenger RNA (mRNA). mRNA carries instructions from genes, in the cell nucleus, to ribosomes in the cell cytoplasm where these instructions are “read†during a synthetic process that culminates in various cell products.
Purposefully designed and created AODNTs may be used as therapeutic agents because of their ability to bind to specific types of mRNA and thereby block the transmission of genetic instructions for the synthesis of various cell products. Alternatively, AODNTs may be used as tools for the study of gene function. AODNTs that have the ability to block two types of mRNA are described as “bispecific.â€
Claims in ‘493 involved a bispecific AODNT capable of binding to mRNA for two types of human Insulin-Dependent Growth Factor Binding Protein (IGFBP), IGFBP-2 and IGFBP-5. The application claimed: 1) a bispecific AODNT, 2) methods for producing pharmaceuticals containing this bispecific AODNT, 3) and methods for treating endocrine-regulated cancers by using the claimed AODNT to prevent production of IGFBP-2 and IGBP-5. The examiner rejected composition claims in ‘493 for the AODNT.
Claims 1 and 4 were cited by the Board as representative of the rejected claims:
1. a bispecific antisense oligodeoxynucleotide, wherein substantially all of the oligodeoxynucleotide is complementary to a portion of a gene encoding human IGFBP-2 and substantially all of the oligodeoxynucleotide is also complementary to a gene encoding human IGFBP-5, and wherein the oligodeoxynucleotide is of sufficient length to act as an antisense inhibitor of human IGFBP-2 and human IGFBP-5.
4. the antisense oligodeoxynucleotide according to claim 1, wherein the oligodeoxynucleotide consists essentially of a series of bases as set forth in any of Seq. ID. Nos. 3 through 7.
The sequences referenced in claim 4 ranged from 18 to 22 bases in length. Gleave elected Sequence No. 5, a twenty-base AODNT, in discussions with the examiner.
The examiner based rejection of the ‘493 composition claims on the published PCT application 00/78341 of Wraight et al. (Wraight). Wraight listed every fifteen-base long sense oligonucleotide in the IGFBP-2 gene and disclosed that: 1) antisense oligonucleotides are preferably between 15 and 25 bases in length, 2) some antisense oligonucleotides maybe bispecific, and 3) "antisense oligonucleotides to IGFBP-2 may be selected from molecules capable of interacting with one or more†of the sense oligonucleotides described in the long list of fifteen-base long sense oligonucleotides disclosed.
The Board found that 1) Wraight “described an oligodeoxynucleotide of sufficient length to act as an antisense inhibitor to human IGFBP-2 and IGFBP-5, . . .†and 2) “substantially all of the oligodeoxynucleotide. . .†was “complementary to a portion of the gene encoding human IGBFP-2 and complementary to the gene encoding human IGFBP-5. . . .†and that Wraight therefore anticipated claim 1. The Board also affirmed rejection of ‘493 for obviousness.
ISSUE
Are claims to a specific AODNT with specific properties anticipated or made obvious by a reference that lists every fifteen-base long sense oligonucleotide in a known nucleic acid sequence?
DECISION
Yes. “The compositions described in ‘493. . . were described in Wraight’s enabling disclosure.†“Gleave’s contribution is, at best, ‘finding a use for the compound, not discovering the compound itself.†In re Schoenwald, 964 F.2d 1122, 1124 (Fed. Cir.).’†The Board’s rejection of claims 1, 4, 15, and 18-21 of ‘493 under § 102 (b) was affirmed without reaching a decision regarding the examiner’s rejection regarding obviousness under § 103. See at 1339.
HOLDINGS
In order for a reference to be anticipatory under § 102 (b) it must 1) disclose each and every element of the claimed invention, explicitly or inherently. See, Eli Lilly & Co. v. Zenith Goldline Pharms., Inc., 471 F.3d 1369, 1375 (Fed. Cir. 2006) and 2) “enable one of ordinary skill in the art to make the invention without undue experimentation.†Impax Labs., Inc. v. Aventis Pharms. Inc., 545 F.3d 1312, (Fed. Cir. 2008). However, “as long as the reference discloses all of the claims limitations and enables the ‘subject matter that falls within the scope of the claims at issue,’ the reference anticipates –no ‘actual creation reduction to practice’ is required.†Schering Corp. v. Geneva Pharms., Inc., 339 F.3d 1373, 1380-81 (Fed. Cir. 2003).
"A reference need disclose no independent use or utility to anticipate a claim under § 102.†Supra at 1336, see also, Novo Nordisk Pharm., Inc. v. Bio-Tech Gen. Corp.., 424 F.3d 1347, 1355 (Fed. Cir. 2005) (‘The standard for enablement of a prior art reference for purposes of anticipation, under § 102 differs from the enablement standard under 35 U.S.C § 112.’). “For method claims, the only way one can show that a reference enables the method is to show that a person of ordinary skill would know how to use — in other words, to practice or carry out — the method in light of the reference. This does not mean, however, that the prior art reference must demonstrate the inventions utility.†Supra at 1336
In Wiggins, 488 F.2d 538, 543, cited by Gleaves for the proposition that “The mere naming of a compound in a reference, without more, cannot constitute a description of the compound. . .†is inapposite to the instant case because methods for synthesizing the compounds listed in Wiggins did not exist until two years after the reference listing them was published. Therefore, listing those compounds could not enable a person of ordinary skill in the art to proceed to synthesize them. However, Wiggins notes that the difference between naming and description, for the purpose of §102, was the ability of a person with ordinary skill in the art to make the claimed compound. In the instant case, both parties agree that the compounds listed by Wraight could be synthesized by a person of ordinary skill in the art at the time of invention. Under these facts, identification of these compounds is a description under §102(b).
“’Whether a prior art reference is enabling is a question of law based upon underlying factual findings.’†Minn. Mining & Mfg. Co. v. Chemque, Inc., 303 F.3d 1294, 1301 (Fed. Cir. 2002).
In considering the differences between lists and genera the court cited Atofina v. Great Lakes Chem. Corp., 441 F.3d 991, 999 for the proposition that “It is well-established that the disclosure of a genus in the prior art is not necessarily the disclosure of every species that is member of the genus.â€, then went on to note “this distinction collapses when the class of compounds that falls within the genus is so limited that a person of ordinary skill in the art can ‘at once envisioned each member of this limited class.’†Eli Lilly, 471 F.3d 1369, 1376.
ANALYSIS
The court found the AODNT composition claims in ‘493 anticipated, under 102(b), because prior art enabled a PHOSITA to make and use the AODNT claimed based on the facts in this case. One of the most important facts, in this regard, was acknowledgement by both parties that, at the time of invention, a PHOSITA would have knowledge needed to synthesize the claimed compound given the limited information provided in Wraight.
This case highlights 1) the extent to which anticipation analysis is fact driven and dependent and 2) the critical differences between written description pertaining to anticipation of the subject matter of a claim under §102(b), and the written description needed to support claims under §112.
Anticipation analysis is dependent on facts such as identification of the PHOSITA, clarification of terms, what the state of the art was at the time of invention, whether an element is inherent in prior art, and even more technical issues, such as filing date, etc.
Prior art must describe every element of a claim, arranged or combined in the same way as the claim, and enable a PHOSITA to make and use the invention without undue experimentation, in order to be anticipatory. Unlike the written description of a claim, however, prior art does not need to describe any proof of utility or understanding of usefulness. It is this differentiation that has caused the court to find, given the right surrounding facts and circumstances, that lists of compounds can stand for anticipatory prior art of a specific compound even without special emphasis of any given compound on the list.
W. Harry Horner WVU Class of 2011
SUMMARY
Composition claims for a an antisense oligodeoxynucleotide that could bind to messenger RNA for two different types of human Insulin-Dependent Growth Factor Binding Protein because of its complementary structure to the genes for these binding proteins were rejected by the patent examiner. The reasons given for rejection were indefiniteness under 35 U.S.C. § 112, anticipation under § 102 and obviousness under § 103. The examiner found the claims invalid based on prior art that provided a long list of sense oligonucleotides and disclosed general concepts that described the claimed compounds.
On appeal, the Board of Patent Appeals and Interferences reversed the rejection for indefiniteness, but affirmed rejection for anticipation and obviousness, finding that the prior art described the claimed compounds. On appeal the Federal Circuit affirmed that the claimed compounds were described adequately in prior art to be synthesized by an ordinary person skilled in the art and were, therefore, anticipated. A decision regarding obviousness was not reached.
PROCEDURAL HISTORY
The patent examiner rejected composition claims 1, 4, 15, and 18-21 of patent application No. 10/346,493 (‘493) as indefinite under 35 U.S.C. § 112, ¶ 2 and as anticipated or obvious under 35 U.S.C. § 102 (b) and § 103 (a) respectively. The United States Patent and Trademark Office Board of Patent Appeals and Interferences ("Board") reversed the rejection under Section 112 and affirmed the rejections under Sections 102 and 103. The rejections due to anticipation and obviousness were appealed.
FACTS
Antisense oligodeoxynucleotides (AODNTs) are short (typically 13-25 nucleotides), single strands of DNA that are complementary to a chosen sequence of DNA or messenger RNA (mRNA). mRNA carries instructions from genes, in the cell nucleus, to ribosomes in the cell cytoplasm where these instructions are “read†during a synthetic process that culminates in various cell products.
Purposefully designed and created AODNTs may be used as therapeutic agents because of their ability to bind to specific types of mRNA and thereby block the transmission of genetic instructions for the synthesis of various cell products. Alternatively, AODNTs may be used as tools for the study of gene function. AODNTs that have the ability to block two types of mRNA are described as “bispecific.â€
Claims in ‘493 involved a bispecific AODNT capable of binding to mRNA for two types of human Insulin-Dependent Growth Factor Binding Protein (IGFBP), IGFBP-2 and IGFBP-5. The application claimed: 1) a bispecific AODNT, 2) methods for producing pharmaceuticals containing this bispecific AODNT, 3) and methods for treating endocrine-regulated cancers by using the claimed AODNT to prevent production of IGFBP-2 and IGBP-5. The examiner rejected composition claims in ‘493 for the AODNT.
Claims 1 and 4 were cited by the Board as representative of the rejected claims:
1. a bispecific antisense oligodeoxynucleotide, wherein substantially all of the oligodeoxynucleotide is complementary to a portion of a gene encoding human IGFBP-2 and substantially all of the oligodeoxynucleotide is also complementary to a gene encoding human IGFBP-5, and wherein the oligodeoxynucleotide is of sufficient length to act as an antisense inhibitor of human IGFBP-2 and human IGFBP-5.
4. the antisense oligodeoxynucleotide according to claim 1, wherein the oligodeoxynucleotide consists essentially of a series of bases as set forth in any of Seq. ID. Nos. 3 through 7.
The sequences referenced in claim 4 ranged from 18 to 22 bases in length. Gleave elected Sequence No. 5, a twenty-base AODNT, in discussions with the examiner.
The examiner based rejection of the ‘493 composition claims on the published PCT application 00/78341 of Wraight et al. (Wraight). Wraight listed every fifteen-base long sense oligonucleotide in the IGFBP-2 gene and disclosed that: 1) antisense oligonucleotides are preferably between 15 and 25 bases in length, 2) some antisense oligonucleotides maybe bispecific, and 3) "antisense oligonucleotides to IGFBP-2 may be selected from molecules capable of interacting with one or more†of the sense oligonucleotides described in the long list of fifteen-base long sense oligonucleotides disclosed.
The Board found that 1) Wraight “described an oligodeoxynucleotide of sufficient length to act as an antisense inhibitor to human IGFBP-2 and IGFBP-5, . . .†and 2) “substantially all of the oligodeoxynucleotide. . .†was “complementary to a portion of the gene encoding human IGBFP-2 and complementary to the gene encoding human IGFBP-5. . . .†and that Wraight therefore anticipated claim 1. The Board also affirmed rejection of ‘493 for obviousness.
ISSUE
Are claims to a specific AODNT with specific properties anticipated or made obvious by a reference that lists every fifteen-base long sense oligonucleotide in a known nucleic acid sequence?
DECISION
Yes. “The compositions described in ‘493. . . were described in Wraight’s enabling disclosure.†“Gleave’s contribution is, at best, ‘finding a use for the compound, not discovering the compound itself.†In re Schoenwald, 964 F.2d 1122, 1124 (Fed. Cir.).’†The Board’s rejection of claims 1, 4, 15, and 18-21 of ‘493 under § 102 (b) was affirmed without reaching a decision regarding the examiner’s rejection regarding obviousness under § 103. See at 1339.
HOLDINGS
In order for a reference to be anticipatory under § 102 (b) it must 1) disclose each and every element of the claimed invention, explicitly or inherently. See, Eli Lilly & Co. v. Zenith Goldline Pharms., Inc., 471 F.3d 1369, 1375 (Fed. Cir. 2006) and 2) “enable one of ordinary skill in the art to make the invention without undue experimentation.†Impax Labs., Inc. v. Aventis Pharms. Inc., 545 F.3d 1312, (Fed. Cir. 2008). However, “as long as the reference discloses all of the claims limitations and enables the ‘subject matter that falls within the scope of the claims at issue,’ the reference anticipates –no ‘actual creation reduction to practice’ is required.†Schering Corp. v. Geneva Pharms., Inc., 339 F.3d 1373, 1380-81 (Fed. Cir. 2003).
"A reference need disclose no independent use or utility to anticipate a claim under § 102.†Supra at 1336, see also, Novo Nordisk Pharm., Inc. v. Bio-Tech Gen. Corp.., 424 F.3d 1347, 1355 (Fed. Cir. 2005) (‘The standard for enablement of a prior art reference for purposes of anticipation, under § 102 differs from the enablement standard under 35 U.S.C § 112.’). “For method claims, the only way one can show that a reference enables the method is to show that a person of ordinary skill would know how to use — in other words, to practice or carry out — the method in light of the reference. This does not mean, however, that the prior art reference must demonstrate the inventions utility.†Supra at 1336
In Wiggins, 488 F.2d 538, 543, cited by Gleaves for the proposition that “The mere naming of a compound in a reference, without more, cannot constitute a description of the compound. . .†is inapposite to the instant case because methods for synthesizing the compounds listed in Wiggins did not exist until two years after the reference listing them was published. Therefore, listing those compounds could not enable a person of ordinary skill in the art to proceed to synthesize them. However, Wiggins notes that the difference between naming and description, for the purpose of §102, was the ability of a person with ordinary skill in the art to make the claimed compound. In the instant case, both parties agree that the compounds listed by Wraight could be synthesized by a person of ordinary skill in the art at the time of invention. Under these facts, identification of these compounds is a description under §102(b).
“’Whether a prior art reference is enabling is a question of law based upon underlying factual findings.’†Minn. Mining & Mfg. Co. v. Chemque, Inc., 303 F.3d 1294, 1301 (Fed. Cir. 2002).
In considering the differences between lists and genera the court cited Atofina v. Great Lakes Chem. Corp., 441 F.3d 991, 999 for the proposition that “It is well-established that the disclosure of a genus in the prior art is not necessarily the disclosure of every species that is member of the genus.â€, then went on to note “this distinction collapses when the class of compounds that falls within the genus is so limited that a person of ordinary skill in the art can ‘at once envisioned each member of this limited class.’†Eli Lilly, 471 F.3d 1369, 1376.
ANALYSIS
The court found the AODNT composition claims in ‘493 anticipated, under 102(b), because prior art enabled a PHOSITA to make and use the AODNT claimed based on the facts in this case. One of the most important facts, in this regard, was acknowledgement by both parties that, at the time of invention, a PHOSITA would have knowledge needed to synthesize the claimed compound given the limited information provided in Wraight.
This case highlights 1) the extent to which anticipation analysis is fact driven and dependent and 2) the critical differences between written description pertaining to anticipation of the subject matter of a claim under §102(b), and the written description needed to support claims under §112.
Anticipation analysis is dependent on facts such as identification of the PHOSITA, clarification of terms, what the state of the art was at the time of invention, whether an element is inherent in prior art, and even more technical issues, such as filing date, etc.
Prior art must describe every element of a claim, arranged or combined in the same way as the claim, and enable a PHOSITA to make and use the invention without undue experimentation, in order to be anticipatory. Unlike the written description of a claim, however, prior art does not need to describe any proof of utility or understanding of usefulness. It is this differentiation that has caused the court to find, given the right surrounding facts and circumstances, that lists of compounds can stand for anticipatory prior art of a specific compound even without special emphasis of any given compound on the list.
W. Harry Horner WVU Class of 2011