From: Marina Larson [e-mail address redacted] Sent: Thursday, May 15, 2014 2:22 PM To: myriad-mayo_2014 Subject: Comments on March 4, 2014 Guidance Having listened to the recent forum on this issue, I imagine you are receiving a great deal of input. I limit my comments therefore to two issues: First, it appears that Question (2) as set forth casts too broad a net. If practiced as suggested, this could result in almost every claim having some element that occurs in nature (water for example) and requiring a complex analysis concerning Question 3, substantially increasing the Examiner's burden in many cases. For example, a claim to a pharmaceutical inhaler might recite housings, and a pressurized container and a valve. It is a law/principle of nature that opening the valve of the pressurized container will cause the inside and outside pressures to try to equalize, expelling contents of the container. Intuitively, it is apparent that an inhaler is an article of manufacture, and not a product of nature; yet the broad form of question (2) could send the examiner on a required exercise of looking at factors. One way to address this would be at a minimum to require an initial determination that there is nothing in the claimed composition other than things that might be found together in nature within the limits of any numerical or functional limitations recited. (Note this would save old fashioned gunpowder, if there was a functional definition or even a common sense understanding that to be gunpowder requires the combined presence of materials in appropriate ratios to go boom.) Second, while many of the examples seem to be pressing the limits, I would in particular comment on the analysis of claim 1 in example E. The example concludes that the primers of claim 1 are judicial exceptions because both are "naturally occurring DNA sequences found on a human chromosome." This conclusion is not required by any case law discussed, including in particular AMP v. Myriad, unless you are stealthily and without explanation applying a broadest reasonable interpretation argument in this example. If the Examiner found in the particular case that the term "primer" was merely a statement of intended use and that the term could (by applying BRI) read on the full coding and non-coding strands of genomic DNA then the analysis has a sound basis in AMP v. Myriad. Unfortunately this guidance is being used to reject short oligonucleotides based on having 100% identity to a part of one of the strands, and this result is contrary to the holding in AMP v. Myriad. AMP v. Myriad expressly held that cDNA was not a product of nature and was patent eligible. cDNA is of course a DNA copy of mRNA. Further, it was understood by the Supreme Court that “cDNA differs from natural DNA in that the non-coding regions have been removed .” Thus, the patent eligible cDNA differs from the original genomic sequence by the removal of parts of the genomic sequence (the introns). This structural change was held to be sufficient for patent eligibility, even though the parts of the genomic sequence that are removed are determined by the naturally occurring structure of the gene, and even though the cDNA encodes the exact same information content as the genomic DNA. An oligonucleotide that is defined to be less than the entire non-coding strand can also be visualized as a genomic sequence from which material has been deleted. In this case, however, the inventor, not the natural structure of the genomic sequence, determined what parts are removed and what parts are retained. Furthermore, the oligonucleotide will generally have some specific and optimized property (such as the ability to bind as a probe or primer in a diagnostic assay, or the ability to cause antisense inhibition of protein formation) that is not found or at least not found to the same extent in the full length sequence. Furthermore, the truncated sequence of the oligonucleotide no longer carries the information of the genomic sequence to encode the complete protein. Thus, the oligonucleotide is structurally different from the genomic sequence by the removal of genetic material (in the same way that cDNA is different from genomic DNA due to removal of material) by the inventor, and has different functions. Thus, it is farther removed from the natural material starting point than cDNA and there is no logical reason to say that it passes back into the realm of patent ineligibility. It appears from the language of the example that there is a problem with conflating the idea of a sequence (as a string of letters) with the molecule that those letters represent. It is entirely true that the string of letter of the oligonucleotide may occur within the longer sequence of chromosomal DNA, but the molecule that those letters represent does not exist as a discrete entity and therefore just like with cDNA, the oligonucleotide/primer is a new molecule that does not exist in nature. It is noted that the conclusion of Question (2) in this case that the primer is a product of nature taints the analysis of the factors (which in this case are a mere repetition of the question (2) conclusion with some explanation not well grounded in AMP v. Myriad as discussed above). It would be better if the answer to question (2) reached the conclusion that the primer was not a product of nature, by applying the markedly different standard at this stage. If the claim element that is derived from a natural product (and that triggers the analysis in the first place) is markedly different (in structure function or both) from the natural product it is being compared to the Answer to question (2) should be No. Then the analysis of factors does not need to be done and waste the examiner's time. If on the other hand, the claim element does seem to be a product of nature (i.e. not markedly different from the natural product to which it is being compared) then the factors or something like them can be considered to see if other elements are present in the claims that make the claimed invention different. This could be additional components (including other actives, formulation limitations or carriers) or concentration limits and the like. Nothing about this should consider whether the additional component is sufficient to make the claimed invention patentable over the natural product to the extent it is part of the prior art. It should solely look at whether it makes the claimed invention different from the judicial exception in a significant/marked manner. Finally, I would reiterate the comments from the forum that the issue of the March 4 Guidance needs to be addressed quickly and with a defined pathway to turn cases already rejected under these standards around for expedited reconsideration. I am already preparing an appeal brief based on the March 4 standards, and have had cases withdrawn from issue to make a §101 rejection. I even have one case that has gone all the way through the Patent Office appeals process once (ALL REJECTIONS REVERSED), and now has a new ground for rejection under § 101 rather than a Notice of Allowance. Should you have any questions or like to discuss this comment, please feel free to contact me. -- Marina T. Larson, Ph.D. Larson & Anderson, LLC phone: +1 970 262 1800 x 152 PO Box 4928 330 Dillon Ridge Way fax: +1 970 262 1809 Dillon, CO 80435 USA