The Golden Rule of Biological Inventions And the Written Description Requirement

Patent practitioners are the legal world's great interpreters. Clients rely on these attorneys for their ability to speak two languages: the language of the law and the language of science. A company with a well-organized in-house legal department can take proactive steps in the growth of the company's intellectual property to ensure that when legal protection is sought in the form of a patent, certain statutory requirements have been met and that the legal instrument through which patent protection is sought (a specification or “the disclosure”) adequately describes the invention. Furthermore, legal counsel can be positioned to provide oversight during the inventive process by focusing researchers' attention on properly documenting patentable ideas. Additionally, among other things, legal counsel can help researchers identify patentable ideas. What might be considered minor and not noteworthy to a researcher may be sufficiently inventive to warrant patent protection. In the biotech or pharmaceutical industry, a strong patent position is often defined not by a single pioneering and patented invention but by numerous smaller inventions comprising a
patent portfolio.

In an ideal world, a business would have a patent practitioner everywhere at once: in the lab, in the office, and in the boardroom. The purpose of this article is to interpret a sphere of patent law related to the description of biological inventions in terms that are practical for researchers and business managers in the biotech industry who live in a non-ideal world. While a proper patent application is best drafted by an experienced patent professional, understanding the requirements of a properly drafted specification can save a business frustration, cost, and the loss of intellectual property protection. In particular, because the “written description” of a patent application is the product of the inventor, a basic legal understanding of the requirements of this section can also inform a researcher's documentation and inventive path, resulting in stronger IP protection.

The Written Description Requirement

IP professionals know that a patent gives the owner the right to exclude others from making, using, or selling a claimed invention for a period of years. In order to obtain a patent, the applicant must first demonstrate that his invention satisfies five requirements under the law: statutory subject matter, utility, written description, novelty, and non-obviousness. These requirements for patent protection are universally required in the United States and are applicable to all forms of invention. When biological inventions are challenged in the courts or by examiners in the patent office often it is because they fail to meet the written description requirement. So what is the written description requirement and what can businesses do to ensure written description rejections/challenges are minimized or eliminated?

The written description requirement is derived under U.S. law from 35 U.S.C. '112 which reads in part:

The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.

The reader will note that when parsed, the requirement directs the applicant to do several things ' one of which is to ensure that the specification contains a written description which enables another skilled person to make the invention. The written description requirement ensures that the applicant had in his or her possession, as of the filing date of the application, the specific subject matter claimed by the applicant. One way to minimize rejections based on this requirement is to follow the golden rule of written description and biological inventions.

Biological Inventions and Nucleotide Sequences

Biological inventions claiming nucleotide sequences ' the bread and butter of the biotech industry ' are prone to failing the written description requirement. A practical example is used to illustrate why. Imagine that a scientist isolates a nucleic acid sequence encoding for a useful biological activity. Such a sequence might look like this:

G G C G C G G C A C C G U C C G C G G A A C A A A C G G

If the scientist were to provide this sequence and its utility in the patent specification and if the sequence is not anticipated or obvious in light of the prior art, the scientist is very likely to get a patent. But a claim to just this sequence may provide little patent protection. Other sequences will encode the same active protein or other proteins sufficiently similar to function substantially the same way. This is because multiple nucleic acid sequences encode for the same amino acids resulting in the same protein structure for certain non-identical sequences. For example “GGC-GCG-GCA,” the first three “three-letter sequences” of the above sequence encode for the polypeptide Glycine-Alanine-Alanine. However, so does GGU-GCU-GCG and a number of other sequences. This ability of multiple sequences to encode for the same amino acid is a result of the so-called degeneracy of the genetic code. Furthermore, even if the scientist were to claim all
“degenerate” variants of the sequence, a large number of homologues
(non-identical and non-degenerate nucleic acid sequences) will
exist that retain the desired activity. Because modification of one or more sequences might not affect the activity of the resulting protein, a potential infringer can avoid infringement by producing similar but not identical nucleic acid sequences.

Claim draftsmen realized this long ago and began drafting claims using language such as:

1. An isolated nucleic acid sequence that encodes a polypeptide with at least 90% amino acid sequence homology to SEQ ID NO: 2.

(SEQ ID NO: 2 is just a placeholder for the nucleic acid sequence given above. In the actual patent specification, a chart or table would identify the nucleic acid sequences and then the claims would refer to the sequence ID number.)

From one point of view, such a claim provides reasonable protection for the scientist's innovation. The claim is not too broad in that it doesn't cover just any variation but is broad enough to protect copycats who wish to avoid infringement by modifying a few sequences here and there. (While the “doctrine of equivalents” might be applicable to such a case, this doctrine is particularly weak in light of court precedent over the years narrowing its scope.) The patent office might have a different perspective: Have you actually claimed a compound having any utility? While some, possibly many of the compounds, have utility in that they have the biological function recited in the specification, the PTO is likely to reject such a claim as lacking substantial utility (one of the statutory requirements for obtaining a patent) because some homologues are likely to be inactive. So the hypothetical inventor has met one statutory requirement but now failed to meet another.

Clever claim draftsmen might amend the claim to read:

1. An isolated nucleic acid
that encodes a polypeptide with at least 90% amino acid sequence identity to SEQ ID NO: 2; wherein the polypeptide has activity X.

Now the claims are directed only to those homologues which have the recited activity and which are at least 90% identical to the claimed sequence. Such a claim amendment still might not be enough however! The PTO will respond, if applicant hasn't followed the golden rule, that the invention has not been sufficiently described. While anyone can quickly determine whether a claimed sequence is at least 90% identical to the base sequence, one might not know which sequences can actually be changed without losing function.

A Real World Example:
Ex parte Porro

These written description requirements were applied in a recent case from the Board of Patent Appeals and Interferences (“BPAI”). In Ex parte Porro, the BPAI held that claims to a method of making vitamin C were invalid for lack of proper written description. The claims at issue described the method as comprising the steps of obtaining a recombinant yeast capable of converting a precursor into vitamin C. Ex parte Porro, Appeal No. 2008-0184 (BPAI, March 11, 2008). This yeast had to contain a “coding region” for an enzyme which was at least 90% homologous to a defined sequence. Of course, the specification only disclosed a single sequence, and the patent examiner concluded that the specification did not adequately describe a genus having 90% homology.

The BPAI affirmed the examiner's rejection of the claim by noting that the specification failed to describe which variants of the sequence are responsible for the activity of the enzyme. In other words, the specification lacked an explanation as to which sequences could be changed without altering the activity of the enzyme. Alternatively, according to the BPAI, the specification could have provided a “representative” number of examples of the genus.

The Golden Rule of Written Description and Biological Inventions

So what does this mean for scientists and the business managers overseeing them? There are at least two worthwhile options: 1) provide as many examples of variants which retain the activity claimed (and those variants which do not retain activity); and/or 2) describe which sequences can or cannot be changed without losing the claimed functionality.

Those overseeing the inventive path of their business' scientists must remember that the patent office will require a description that provides a guide for others to follow in order to make functional variants of a sequence if the claims are directed to homologues. Accordingly, scientists must be reminded to document all experiments, including failed ones, to include in the specification to show a pattern of functionality. In other words, the inventor must be able to provide a specification that indicates to some degree whether a given random homologue will be active or not. If the inventor is aware of which residues need to be conserved to maintain functionality, this also should be recorded and disclosed in the specification. If the tertiary structure of a protein and its active site is known, then this should also be included.

Finally, the above discussion can be boiled down to or “described” by a single golden rule: If one has information relating structure and function, place it in the specification. Inventors often think that because it would be easy to test for the activity of a polypeptide, thereby determining whether a sequence is functional or not, that a written description of functional variants is not necessary. This is a mistake one cannot afford to make. After a specification has been filed, adding such information will result in a new matter rejection. Scientists must be reminded that an ability to test for activity cannot substitute for the lack of a written description which correlates structure with activity. So while some may say “less is more,” when it comes to describing biological inventions “more is more.”

Patent practitioners are the legal world's great interpreters. Clients rely on these attorneys for their ability to speak two languages: the language of the law and the language of science. A company with a well-organized in-house legal department can take proactive steps in the growth of the company's intellectual property to ensure that when legal protection is sought in the form of a patent, certain statutory requirements have been met and that the legal instrument through which patent protection is sought (a specification or “the disclosure”) adequately describes the invention. Furthermore, legal counsel can be positioned to provide oversight during the inventive process by focusing researchers' attention on properly documenting patentable ideas. Additionally, among other things, legal counsel can help researchers identify patentable ideas. What might be considered minor and not noteworthy to a researcher may be sufficiently inventive to warrant patent protection. In the biotech or pharmaceutical industry, a strong patent position is often defined not by a single pioneering and patented invention but by numerous smaller inventions comprising a
patent portfolio.

In an ideal world, a business would have a patent practitioner everywhere at once: in the lab, in the office, and in the boardroom. The purpose of this article is to interpret a sphere of patent law related to the description of biological inventions in terms that are practical for researchers and business managers in the biotech industry who live in a non-ideal world. While a proper patent application is best drafted by an experienced patent professional, understanding the requirements of a properly drafted specification can save a business frustration, cost, and the loss of intellectual property protection. In particular, because the “written description” of a patent application is the product of the inventor, a basic legal understanding of the requirements of this section can also inform a researcher's documentation and inventive path, resulting in stronger IP protection.

The Written Description Requirement

IP professionals know that a patent gives the owner the right to exclude others from making, using, or selling a claimed invention for a period of years. In order to obtain a patent, the applicant must first demonstrate that his invention satisfies five requirements under the law: statutory subject matter, utility, written description, novelty, and non-obviousness. These requirements for patent protection are universally required in the United States and are applicable to all forms of invention. When biological inventions are challenged in the courts or by examiners in the patent office often it is because they fail to meet the written description requirement. So what is the written description requirement and what can businesses do to ensure written description rejections/challenges are minimized or eliminated?

The written description requirement is derived under U.S. law from 35 U.S.C. '112 which reads in part:

The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.

The reader will note that when parsed, the requirement directs the applicant to do several things ' one of which is to ensure that the specification contains a written description which enables another skilled person to make the invention. The written description requirement ensures that the applicant had in his or her possession, as of the filing date of the application, the specific subject matter claimed by the applicant. One way to minimize rejections based on this requirement is to follow the golden rule of written description and biological inventions.

Biological Inventions and Nucleotide Sequences

Biological inventions claiming nucleotide sequences ' the bread and butter of the biotech industry ' are prone to failing the written description requirement. A practical example is used to illustrate why. Imagine that a scientist isolates a nucleic acid sequence encoding for a useful biological activity. Such a sequence might look like this:

G G C G C G G C A C C G U C C G C G G A A C A A A C G G

If the scientist were to provide this sequence and its utility in the patent specification and if the sequence is not anticipated or obvious in light of the prior art, the scientist is very likely to get a patent. But a claim to just this sequence may provide little patent protection. Other sequences will encode the same active protein or other proteins sufficiently similar to function substantially the same way. This is because multiple nucleic acid sequences encode for the same amino acids resulting in the same protein structure for certain non-identical sequences. For example “GGC-GCG-GCA,” the first three “three-letter sequences” of the above sequence encode for the polypeptide Glycine-Alanine-Alanine. However, so does GGU-GCU-GCG and a number of other sequences. This ability of multiple sequences to encode for the same amino acid is a result of the so-called degeneracy of the genetic code. Furthermore, even if the scientist were to claim all
“degenerate” variants of the sequence, a large number of homologues
(non-identical and non-degenerate nucleic acid sequences) will
exist that retain the desired activity. Because modification of one or more sequences might not affect the activity of the resulting protein, a potential infringer can avoid infringement by producing similar but not identical nucleic acid sequences.

Claim draftsmen realized this long ago and began drafting claims using language such as:

1. An isolated nucleic acid sequence that encodes a polypeptide with at least 90% amino acid sequence homology to SEQ ID NO: 2.

(SEQ ID NO: 2 is just a placeholder for the nucleic acid sequence given above. In the actual patent specification, a chart or table would identify the nucleic acid sequences and then the claims would refer to the sequence ID number.)

From one point of view, such a claim provides reasonable protection for the scientist's innovation. The claim is not too broad in that it doesn't cover just any variation but is broad enough to protect copycats who wish to avoid infringement by modifying a few sequences here and there. (While the “doctrine of equivalents” might be applicable to such a case, this doctrine is particularly weak in light of court precedent over the years narrowing its scope.) The patent office might have a different perspective: Have you actually claimed a compound having any utility? While some, possibly many of the compounds, have utility in that they have the biological function recited in the specification, the PTO is likely to reject such a claim as lacking substantial utility (one of the statutory requirements for obtaining a patent) because some homologues are likely to be inactive. So the hypothetical inventor has met one statutory requirement but now failed to meet another.

Clever claim draftsmen might amend the claim to read:

1. An isolated nucleic acid
that encodes a polypeptide with at least 90% amino acid sequence identity to SEQ ID NO: 2; wherein the polypeptide has activity X.

Now the claims are directed only to those homologues which have the recited activity and which are at least 90% identical to the claimed sequence. Such a claim amendment still might not be enough however! The PTO will respond, if applicant hasn't followed the golden rule, that the invention has not been sufficiently described. While anyone can quickly determine whether a claimed sequence is at least 90% identical to the base sequence, one might not know which sequences can actually be changed without losing function.

A Real World Example:
Ex parte Porro

These written description requirements were applied in a recent case from the Board of Patent Appeals and Interferences (“BPAI”). In Ex parte Porro, the BPAI held that claims to a method of making vitamin C were invalid for lack of proper written description. The claims at issue described the method as comprising the steps of obtaining a recombinant yeast capable of converting a precursor into vitamin C. Ex parte Porro, Appeal No. 2008-0184 (BPAI, March 11, 2008). This yeast had to contain a “coding region” for an enzyme which was at least 90% homologous to a defined sequence. Of course, the specification only disclosed a single sequence, and the patent examiner concluded that the specification did not adequately describe a genus having 90% homology.

The BPAI affirmed the examiner's rejection of the claim by noting that the specification failed to describe which variants of the sequence are responsible for the activity of the enzyme. In other words, the specification lacked an explanation as to which sequences could be changed without altering the activity of the enzyme. Alternatively, according to the BPAI, the specification could have provided a “representative” number of examples of the genus.

The Golden Rule of Written Description and Biological Inventions

So what does this mean for scientists and the business managers overseeing them? There are at least two worthwhile options: 1) provide as many examples of variants which retain the activity claimed (and those variants which do not retain activity); and/or 2) describe which sequences can or cannot be changed without losing the claimed functionality.

Those overseeing the inventive path of their business' scientists must remember that the patent office will require a description that provides a guide for others to follow in order to make functional variants of a sequence if the claims are directed to homologues. Accordingly, scientists must be reminded to document all experiments, including failed ones, to include in the specification to show a pattern of functionality. In other words, the inventor must be able to provide a specification that indicates to some degree whether a given random homologue will be active or not. If the inventor is aware of which residues need to be conserved to maintain functionality, this also should be recorded and disclosed in the specification. If the tertiary structure of a protein and its active site is known, then this should also be included.

Finally, the above discussion can be boiled down to or “described” by a single golden rule: If one has information relating structure and function, place it in the specification. Inventors often think that because it would be easy to test for the activity of a polypeptide, thereby determining whether a sequence is functional or not, that a written description of functional variants is not necessary. This is a mistake one cannot afford to make. After a specification has been filed, adding such information will result in a new matter rejection. Scientists must be reminded that an ability to test for activity cannot substitute for the lack of a written description which correlates structure with activity. So while some may say “less is more,” when it comes to describing biological inventions “more is more.”