1 The word “polymorphisms” means “many forms”. When used in a biological sense, polymorphisms are genetically determined differences. Although polymorphisms could encompass virtually any detectable trait, the polymorphisms of most interest and usefulness are those at the molecular level. Such polymorphisms are detected by differences in nucleotide sequence.

2 see for examples, Kan and Dozy Proc. Natl. Acad. Sci. USA 75: 5631-5635 (1978); Little et al. Nature 285: 144-147 (1980); Wainwright et al. Am J Hum Genet. 41:944-947 (1987).

3 Coincidentally, the first author on this paper is also one of the authors of this patent analysis. Nottenburg, St John and Weissman, J. Immunol. 139: 1718-1726. The use of non-coding region polymorphisms to mark a chromosome was dictated by the limitations of genomic cloning of large DNA fragments.

4 The phrase “junk DNA” is attributed to Dr Susumu Ohno, a very highly-regarded researcher at the City of Hope in Duarte, California. In 1972, in an attempt to explain the paradox that there was much more coding capacity in genomes than the number of genes, Dr Ohno proposed that much of the genome of more advanced eukaryotes was functionless. He called this DNA “garbage” or “junk” DNA. (see, Gregory, T.R. 2002, “The C-value enigma”, Ph.D. Thesis, Dept. of Zoology, University of Guelph, Ontario, Canada, 894 pp,  especially Chapter 1 for a historical account:

5 Dr Simons has thoroughly reviewed his travels in arriving at the subject invention (www.junkDNA Only a brief synopsis will be presented here.

6 A “haplotype” is a set of closely linked genetic markers present on one chromosome which tend to be inherited together (not easily separable by recombination). The term “haplotype” has been extensively used in immunogenetics in referring to the linked genes in the MHC. See

7 For information on the purpose of the various sections,

8 The term “prosecution history” refers to the “back and forth” negotiation of the claim language and scope between the patent owner and his/her attorney and the Patent Office.

9 The Assignee on the printed patent is GeneType AG, but due to corporate structure changes the patent was reassigned to Genetic Technologies Ltd., an Australian company.

10 This patent would have a term of 17 years from the date of issuance except that the term beyond 9 Mar 2010 was waived. Waivers (called terminal disclaimers) result from an “obviousness-type double patenting” rejection by the Patent Office. This means that at least one claim in this patent was deemed obvious over a claim in a related patent, which expires 9 Mar 2010. The rejection is overcome by disclaiming the length of term beyond the already granted patent. An additional requirement is that the two patents must remain co-owned.

11 The patent text uses the term “intron” in an unconventional way – to mean non-coding DNA (see col. 5, lines 40-50).

12 Only one invention can be granted protection in a patent. Thus, if the claims cover more than one invention, the applicant must choose one of the inventions to prosecute. The remaining inventions can be pursued in what are called divisional patent applications. The United States Patent and Trademark Office rules on multiple inventions are very strict. For example, nucleotides encoding a protein and the protein are considered two separate inventions.

13 Only the main rejections of each examination report (Office Action) are discussed. Other rejections, if any, that are less germane to the thrust of this report are not discussed.

14 Paper No. 7, Amendment, filed 12 Dec 1990, p. 6.

15 Paper No. 13, Amendment submitted 6 May 1991, p. 4.

16 Claims are also directed to the specific case of the invention applied to MHC alleles.

17 Paper No. 11, Amendment submitted 6 May 1991, p. 8.

18 Ibid, p. 9.

19 Paper No. 5, Supplementary Preliminary Amendment, submitted 4 January 1993.

20 Markman v. Westview Instr., Inc., 29 F.3d 1555 (Fed. Cir. 1994).

21 Only in rare circumstances does the use of “a” or “an” limit the number to only one.

22 Paper No. 19, Amendment filed 12 Feb 1992, p. 9.

23 This definition is a classic example of a patentee drafting his own definition, an allowable condition except when the definition is contrary to common usage. Because the Examiner correctly determined that “intron” is commonly used to refer to DNA sequences only between coding regions of a gene, the term was changed to “non-coding region sequence”, which is consistent with common usage.

24 Paper No. 11, Amendment submitted 6 May 1991 in 07/551,239, p.5.

25 In the section “Screening Analysis for Genetic Disease”, the inventors state that the method can “detect genetic diseases that are not associated with coding region variations but are found in regulatory or other untranslated regions of the genetic locus.”

26 supra

27 While the term “non-coding region” is not explicitly defined, the term “intron” refers to the untranslated DNA sequences between exons, along with 5’ and 3’ regulatory and transcribed, but untranslated, regions. Furthermore, the term intron encompasses DNA located between genetic loci. The Examiner objected to the non-conventional use of the term “intron”; the Applicant substituted the term “non-coding region for “intron”. For the sake of this report, we assume that the terms “non-coding” and “intron” are synonymous.

28 Column 6, lines 10-15.

29 Nothing excludes the possibility that one of the primers anneals to an exon sequence and the other of the pair anneals to a non-coding region.

30 Column 9, lines 19-29.

31 “A trait, quality or property or a group of them distinguishing an individual, group, or type.” Webster’s Dictionary.

32 Column 4, lines 44-48.

33 See section “Length of sequence” bridging columns 7 and 8.