Unity of Invention: Biotech Examples

1. Unity of Invention: Biotech Examples TC1600 Special Program Examiner Julie Burke (571)272-0512

2. PATENT COOPERATION TREATY (PCT) INTERNATIONAL SEARCH AND PRELIMINARY EXAMINATION GUIDELINES Guidelines for the Processing by International Searching and Preliminary Examining Authorities of International Applications Under the Patent Cooperation Treatyas in force as from March 25, 2004. Applies to all international applications filed on or after Jan. 1, 2004. Available at http://www.wipo.int/pct/en/texts/pdf/ispe.pdf

3. PCT Rule 13.2 (10.01)* With respect to a group of inventions claimed in an international application, unity of invention exists only when there is a technical relationship among the claimed inventions involving one or more of the same or corresponding special technical features. The expression “special technical features” is defined in PCT Rule 13.2 as meaning those technical features that define a contribution which each of the inventions, considered as a whole, makes over the prior art. * (10.01) refers to chapter 10, paragraph 1 of the ISPE Guidelines

4. PCT Rule 13.2 requires that the group shares a technical feature and (2) the technical feature makes a contribution over the prior art.

5. Lack of unity may be evident • a priori, before consideration of prior art, because the groups do not share a same or corresponding technical feature • a posteriori, after a search of the prior art, because the shared technical feature fails to make a contribution over the prior art

6. Additional Considerations • Contribution over the prior art is considered with respect to novelty and inventive step (10.02) • Unity of invention is considered in relation to the independent claims (10.06)

7. Three Particular Situations • Different categories of inventions (10.12) • So-called “Markush Practice” (10.17) • Intermediate and final products (10.18)

8. Markush Practice All alternatives are of similar nature when they (A) have a common property or activity and (B1) have a common structure, that is, a significant structural element or (B2) belong to a recognized class of chemical compounds.

9. Common structure is defined as one which • Occupies a large portion of the structure or • Occupies a small portion which makes a contribution over the prior art

10. Recognized class of chemical compounds • Expectation from the knowledge in the art that members of the class will behave in the same way, that is, each member could be substituted one for another with the expectation that the same result would be achieved. • Note that PCT Rule 13.2 also requires that the shared feature must make a contribution over the prior art.

11. Example 32: Multiple Structurally and Functionally Unrelated Polynucleotides (10.52) Claim 1. An isolated polynucleotide selected from the group consisting of nucleotide sequences SEQ ID Nos: 1-10. • SEQ ID Nos 1-10 are 500 bp cDNAs obtained from human liver. The sequences are not homologous to each other. They can be used as probes to obtain full-length DNAs, although there is no description of the function or biological activity of the corresponding proteins. There is no prior art available. A human liver cDNA library had not been established before.

12. Example 32, continued, analysis The polynucleotides would have unity of invention if they had a common property or activity and shared a significant structural element. • The polynucleotides fail to share a common property or activity. A probe of SEQ ID NO 1 could not be used to isolate SEQ ID Nos 2-10. • The polynucleotides fail to share a significant structural element. The sugar phosphate backbone of a nucleic acid chain is not considered to be a significant structural element since it is shared by all nucleic acid molecules. No other regions of homology are described. • Isolation of the polynucleotides from a single source (human liver) is not sufficient to meet criteria for unity of invention. Inventions could be grouped as: Inventions 1-10: Polynucleotides having SEQ ID Nos 1-10, respectively.

13. Example 33: Multiple Structurally and Functionally Related Polynucleotides (10.53) Claim 1. An isolated polynucleotide selected from the group consisting of nucleotide sequences SEQ ID Nos: 1-10. • SEQ ID Nos: 1-10 share a significant structural element and their corresponding mRNAs are expressed only in hepatocytes of patients with disease Y. There is no prior art available. The shared structural element had not been identified before, nor had any link been established between genes expressing mRNA containing that structural element and patients afflicted with disease Y.

14. Example 33, continued, analysis The polynucleotides would have unity of invention if they shared • a common property or activity, • a significant structural element and • a technical feature which made a contribution over the prior art. • SEQ ID Nos 1-10 share a common property: expression of an mRNA present only in patients afflicted with disease Y. • SEQ ID Nos 1-10 share a significant structural element which may be used as the probe to detect mRNA of patients afflicted with disease Y. • There is no prior art found on the shared structural element. Therefore, SEQ ID Nos 1-10 meet the requirement for unity of invention.

15. Example 36: Multiple nucleic acid molecules which share a common structure and encode proteins with common property (10.56) Claim 1. An isolated nucleic acid selected from SEQ ID No 1, 2 or 3. • The three nucleic acids encode dehydrogenases that include a conserved sequence motif defining the catalytic site and the dehydrogenase function of these proteins. • The three nucleic acids, isolated from mouse, rat and human, are homologous based upon their overall sequence similarity (85-95%) at both the nucleotide and amino acid sequence levels. The prior art describes a nucleic acid from monkeys which is 90% similar and includes the catalytic site defined by the conserved motif.

16. Example 36, continued, analysis The nucleic acid molecules would have unity of invention if they shared a common property or activity and shared a significant structural element. Rule 13.2 requires that the technical feature shared among the inventions defines a contribution over the prior art. • SEQ ID Nos 1-3 share a common property of encoding dehydrogenases. • SEQ ID Nos 1-3 share a significant structural element, the conserved motif. However, a nucleic acid molecule which encodes a dehydrogenase with this conserved motif has already been isolated. Unity of invention is lacking, a posteriori. If no prior art were found, unity of invention would have been accepted.

17. Example 38. Method of screening and compounds identified by the method. (10.58) Claim 1. A method to identify compounds that are antagonists of receptor R, comprising the steps of… Claim 2. Compound X, having formula 1. Claim 3. Compound Y, having formula 2. Claim 4. Compound Z, having formula 3. • Compounds X, Y and Z all act as receptor R antagonists. • Compounds X, Y and Z fail to share any significant structural element. The method steps of Claim 1 involve observing any change in the binding of R’s natural ligand in the presence of a candidate molecule. Receptor R, its biological function and its natural ligand are known in the prior art. No compounds which function as antagonists of receptor R are known.

18. Example 38, continued, analysis A product can have unity of invention with a method of making or method of using the product. See Categories of Invention, 10.12 • A screening method is not a method of making or using the product. • There is no single general concept that links the method to the claimed compounds. The antagonists would have unity of invention with each other, a priori, if they shared a common property or activity and shared a significant structural element. • Although the antagonists share a common property, they fail to share a common structure. For these two reasons, unity is lacking between method and products and among the products.

19. Example 38, continued, possible groupings Group 1, claim 1, method to identify compounds. Group 2, claim 2, compound X. Group 3, claim 3, compound Y. Group 4, claim 4, compound Z.

20. Example 39: Protein and its Encoding DNA (10.59) Claim 1. Isolated protein X having SEQ ID No: 1. Claim 2. Isolated DNA molecule encoding protein X of claim 1. • Protein X is defined by a specific structure, SEQ ID No 1. • The disclosure sets forth a DNA molecule having SEQ ID No 2 which encodes SEQ ID No 1. There is no prior art.

21. Example 39, continued, analysis Rule 13.2 requires that the inventions share a same or corresponding technical feature and that the technical feature shared between the inventions defines a contribution over the prior art. • Because the DNA molecule encodes the protein X, the DNA and protein shared a corresponding technical feature and have unity, a priori. • Because there is not prior art on the protein or the DNA, the DNA and protein share a special technical feature. If prior art existed teaching either the protein X or DNA encoding protein X, the corresponding technical feature would not make a contribution over the prior art and unity would be lacking, a posteriori.

22. Example 39, continued, analysis If alternative DNA claims were presented that encompassed a DNA molecule that did not encode protein X, the claims would not share the same or corresponding technical feature. Examples of such claims follow: • Isolated DNA molecule encoding protein X or a DNA fragment thereof. • Isolated DNA molecule having SEQ ID No 2, or a DNA molecule which hybridizes to SEQ ID No 2 under stringent conditions. DNA inventions including these types of claims would lack unity with the protein group because they would not share a same or corresponding technical feature.

23. Three other examples of interest • Example 34: Functionally unrelated single nucleotide polymorphisms (SNPs) (10.54) • Example 35: Molecules which share a common function not linked to a common structure (10.55) • Example 37: DNA encoding Receptors with partial structural identity and asserted common property (10.57)

24. Summary Unity of Invention is accepted when • the group shares a technical feature- this may be determined a priori, before consideration of prior art and, if a shared technical feature exists, • the technical feature makes a contribution over the prior art- this may be determined a posteriori, after a search of the prior art.