Full opinion text
MEMORANDUM & ORDER MARILYN HALL PATEL, District Judge. The Board of Trustees of the Leland Stanford Junior University (“Stanford”) brought this action against Roche Molecular Systems, Inc., et al. (collectively “Roche”), alleging infringement of various U.S. Patents. Now before the court is Roche’s Motion for Summary Judgment on Invalidity of the asserted patents. Having considered the parties’ arguments and submissions, and for the reasons set forth below, the court rules as follows. BACKGROUND This patent dispute concerns the application of Polymerase Chain Reaction (“PCR”) technology in the context of research related to the Human Immunodeficiency Virus (“HIV”) and the Acquired Immunodeficiency Syndrome (“AIDS”). Stanford currently owns three patents entitled “Polymerase Chain Reaction Assays for Monitoring Antiviral Therapy and Making Therapeutic Decisions in the Treatment of Acquired Immunodeficiency Syndrome.” United States Patent Nos. 5,968,730 (“the '730 patent”); 6,503,705 (“the '705 patent”); 7,129,041 (“the '041 patent”). The patents involve correlating measurements of HIV nucleic acids obtained via a PCR assay with determining whether or not a particular therapy is effective. Claims 1, 5-9, 13-14,18-19 and 23 of the '730 patent, Claims 1 and 5-10 of the '705 patent and Claims 1-4 and 8 of the '041 patent are asserted in this litigation. In general, there are two types of method claims in these patents. The first type includes a step for measuring the HIV copy number. See '730 patent, claims 9, 14, 19; '705 patent, claims 1, 8. For example, claim 9 of the '730 patent reads: 9. A method of evaluating the effectiveness of anti-HIV therapy of a patient comprising (i) collecting a plasma sample from an HIV-infected patient who is being treated with an antiretroviral agent; (ii) amplifying the HIV-encoding nucleic acid in the plasma sample using HIV primers in about 30 cycles of PCR; and (iii) measuring the HIV RNA copy number using the product of the PCR, in which an HIV RNA copy number greater than about 500 per 200 ul of plasma correlates positively with the conclusion that the antiretroviral agent is therapeutically ineffective. The other type of method claims do not include a measuring step, but instead include a step testing for the presence or absence of detectable HIV-encoding nucleic acid. See '730 patent, claims 1, 6, 7, 8; '041 Patent, claim 1. For example, claim 1 of the '041 patent reads: 1. A method of evaluating the effectiveness of anti-HIV therapy of a patient comprising correlating the presence or absence of detectable HIV-encoding nucleic acid in a plasma sample of an HIV infected patient with an absolute CD4 count, wherein the presence or absence of said detectable HIV-encoding nucleic acid is determined by (i) collecting a plasma sample[ ] from an HIV-infected patient who is being treated with an antiretroviral agent; (ii) amplifying HIV-encoding nucleic acid that may be present in the plasma sample using HIV primers via PCR and; (iii) testing for the presence of HIV-encoding nucleic acid sequence in the product of the PCR. All three patents-in-suit issued from the same patent application, filed in May 1992. LEGAL STANDARD I. Summary Judgment Summary judgment is proper when the pleadings, discovery and affidavits show that there is “no genuine issue as to any material fact and that the moving party is entitled to judgment as a matter of law.” Fed.R.Civ.P. 56(c). Material facts are those which may affect the outcome of the case. Anderson v. Liberty Lobby, Inc., 477 U.S. 242, 248, 106 S.Ct. 2505, 91 L.Ed.2d 202 (1986). A dispute as to a material fact is genuine if there is sufficient evidence for a reasonable jury to return a verdict for the nonmoving party. Id. The party moving for summary judgment bears the burden of identifying those portions of the pleadings, discovery and affidavits that demonstrate the absence of a genuine issue of material fact. Celotex Corp. v. Catrett, 477 U.S. 317, 323, 106 S.Ct. 2548, 91 L.Ed.2d 265 (1986). On an issue for which the opposing party will have the burden of proof at trial, the moving party need only point out “that there is an absence of evidence to support the non-moving party’s case.” Id. at 325, 106 S.Ct. 2548. Once the moving party meets its initial burden, the nonmoving party must go beyond the pleadings and, by its own affidavits or discovery, “set out specific facts showing a genuine issue for trial.” Fed. R.Civ.P. 56(e)(2). Mere allegations or denials do not defeat a moving party’s allegations. Id.; Gasaway v. Nw. Mut. Life Ins. Co., 26 F.3d 957, 959-60 (9th Cir.1994). The court may not make credibility determinations, and inferences to be drawn from the facts must be viewed in the light most favorable to the party opposing the motion. Masson v. New Yorker Magazine, 501 U.S. 496, 520, 111 S.Ct. 2419, 115 L.Ed.2d 447 (1991); Anderson, 477 U.S. at 255, 106 S.Ct. 2505. II. Invalidity Based on Obviousness Under Section 103 35 U.S.C. section 103(a) requires that a patent be nonobvious to one skilled in the art at the time the patent issues. This section provides: A patent may not be obtained though the invention is not identically disclosed or described as set forth in [35 U.S.C. section 102], if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Once the patent issues, each claim in an issued patent is presumed valid. 35 U.S.C. § 282. To prove that a patented invention is invalid as obvious, the party asserting invalidity must identify prior art references “which alone or combined with other references would have rendered the invention obvious to one of ordinary skill in the art at the time of invention.” Al-Site Corp. v. VSI Int’l, Inc., 174 F.3d 1308, 1323 (Fed.Cir.1999) (citations omitted). The relevant “question is not whether the combination was obvious to the patentee but whether the combination was obvious to a person with ordinary skill in the art.” KSR Int’l Co. v. Teleflex Inc., 550 U.S.-, 127 S.Ct. 1727, 1742, 167 L.Ed.2d 705 (2007). When a patent is challenged as being invalid, the moving party must prove a claim of obviousness by clear and convincing evidence. Oakley, Inc. v. Sunglass Hut Int’l, 316 F.3d 1331, 1339 (Fed.Cir.2003). The question of “[o]bviousness is a question of law premised on underlying findings of fact.” Eolas Techs. Inc. v. Microsoft Corp., 399 F.3d 1325, 1332 (Fed.Cir.2005), cert denied, 546 U.S. 998, 126 S.Ct. 568, 163 L.Edüd 499 (2005) (citing Graham v. John Deere Co., 383 U.S. 1, 17-18, 86 S.Ct. 684, 15 L.Ed.2d 545 (1966)). These fact questions are: 1) the scope and content of the prior art; 2) the differences between the prior art and the claims at issue; 3) the level of ordinary skill in the art; and 4) secondary evidence of nonobviousness. Graham, 383 U.S. at 17-18, 86 S.Ct. 684; Para-Ordnance Mfg., Inc. v. S.Ct. Imps. Int’l, Inc., 73 F.3d 1085, 1087-88 (Fed.Cir.1995). In Graham, the Supreme Court noted the difficulties in applying the nonobviousness test. 383 U.S. at 18, 86 S.Ct. 684. As a result of these difficulties, the Supreme Court had reason to recently revisit the obviousness analysis. In KSR, the Supreme Court clarified the test for obviousness, criticizing the teaching, suggestion or motivation (“TSM”) standard previously formulated by the Federal Circuit. The Court pointed out that the TSM test should be utilized as a “helpful insight,” rather than a rigid formula and held that “the analysis need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ.” KSR, 127 S.Ct. at 1741. The Court further emphasized the need for courts to value “common sense” over “[rjigid preventative rules,” id. at 1741-42, commenting that “[t]he obviousness analysis cannot be confined by a formalistic conception of the words teaching, suggestion, and motivation, or by overemphasis on the importance of published articles and the explicit content of issued patents,” id. at 1741. The Court also noted the importance of an articulated reasoning regarding obviousness: Often, it will be necessary for a court to look to interrelated teachings of multiple patents; the effects of demands known to the design community or present in the marketplace; and the background knowledge possessed by a person having ordinary skill in the art, all in order to determine whether there was an apparent reason to combine the known elements in the fashion claimed by the patent at issue. To facilitate review, this analysis should be made explicit. Id. at 1740-41 (internal citations omitted). Before the Supreme Court decided KSR, the Federal Circuit emphasized the flexibility of the TSM analysis in DyStar Textilfarben GmbH & Co. Deutschland KG v. C.H. Patrick Co., 464 F.3d 1356 (Fed.Cir.2006), cert. denied, — U.S.-, 127 S.Ct. 2937, 168 L.Ed.2d 262 (2007). There the Federal Circuit held that the “suggestion test is in actuality quite flexible and not only permits, but requires, consideration of common knowledge and common sense.” Id. at 1367. Furthermore, the Federal Circuit acknowledged the possibility of an implicit motivation to combine — one not explicitly apparent in the prior art: “[i]f, as is usually the case, no prior art reference contains an express suggestion to combine references, then the level of ordinary skill will often predetermine whether an implicit suggestion exists.” Id. at 1370. Thus, a high-skill level renders a finding of implicit motivation more likely, as skilled individuals are more likely to combine references “without being told to do so.” Id. Accordingly, this court’s analysis of the parties’ arguments regarding obviousness must be explicit, flexible and guided by common sense. DISCUSSION Roche argues that an article published in 1991 in the Journal of Infectious Diseases renders Stanford’s asserted patents invalid as obvious. See Damstedt Dec., Exh. 10 (hereinafter “JID article”). The JID article describes an assay for quanti-tating HIV RNA using PCR, which comprises of five steps: 1) extraction of the HIV RNA from serum or plasma (“extraction”); 2) copying the single-stranded HIV RNA into a double-stranded DNA molecule (“reverse transcription”); 3) using PCR to make millions of copies of the DNA using primers (“amplification”); 4) detecting the amplified DNA using a DNA probe (“detection”); and 5) generation of a standard curve used to calculate the amount of virus in a patient’s blood using a cRNA standard (“quantitation”). Contents of the JID article were presented at the UCLA Keystone Symposium on Molecular and Cell Biology in 1990 and at the Sixth International AIDS Conference in San Francisco in 1990. See Docket No. 157 at 6:18-21. The presentations conclude that the authors have demonstrated that HIV viral RNA can be detected and quantified in patient serum and that such quantitation “may be a useful marker for disease progression or monitoring antiviral therapy.” Id. at 6:25-7:2. The JID article, which is statutory prior art, discloses the same PCR HIV assay that is disclosed in the asserted patents. Roche asserts that the JID article differs from the asserted patents only to the extent that the patent claims teach the use of this assay to determine therapy effectiveness using results of the assay performed on patients receiving drug therapy. Stanford argues that Roche’s perfunctory analysis, limited to two specific articles, fails to take into account the entirety of the scope and content of the prior art at the time the patents issued, in contravention of Graham, 383 U.S. 1, 86 S.Ct. 684, and that numerous fact issues preclude summary judgment on this issue. This court will first go through an explicit and thorough evaluation of the Graham factors including any factual issues presented, before analyzing how these factors assist in determining whether the claimed methods were obvious to one skilled in the art at the relevant time. I. Graham factors A. Scope and Content of Prior Art Prior art references should be considered in whole to determine the disclosed teachings. Bausch & Lomb, Inc. v. Barnes-Hind/Hydrocurve, Inc., 796 F.2d 443, 448-49 (Fed.Cir.1986). Prior art is pertinent if it is “within the field of the inventor’s endeavor,” or if the reference “logically would have commended itself to an inventor’s attention in considering” the particular problem the inventor was attempting to solve. Princeton Biochems., Inc. v. Beckman Coulter, Inc., 411 F.3d 1332, 1339 (Fed.Cir.2005) (citations omitted). Stanford asserts that at the time of invention, the understanding and teachings of those skilled in the art contradicted and taught away from the idea that HIV RNA could be detected and quantified as an effective marker of HIV infection and therapy effectiveness. Stanford contends that the prevailing theories taught that monitoring disease progression and drug efficacy would effectively result from observing the stable, proviral HIV DNA— not HIV RNA. Minimally, Stanford contends, these contradictory theories create a genuine issue of material fact sufficient to preclude summary judgment. Roche focuses the bulk of its argument on the JID article, which discloses the results and conclusions from tests attempting to detect and quantify HIV RNA in blood serum from HIV-infected patients not undergoing antiretroviral therapy. The article teaches that HIV RNA in serum can be detected and quantified, and it outlines the parameters for such quantification of DNA and RNA. JID article, supra note 2, at 865. The JID article also discloses a relationship between CD4 counts and PCR measurement of HIV RNA. Id. at 864 (“[s]erum from patients with <400 CD4 cells/mm was more likely to be PCR-positive”)- The authors concluded that: these findings provide evidence that the amount of cell-free virus in circulation correlates with the presence of HTV infectious titer ... and the presence of HIV-related symptoms.... Serum PCR may provide an additional marker of disease progression and drug efficacy that could improve our ability to monitor the course of HIV infection. Further studies will be necessary to validate this approach. Id. at 865 (emphasis added). While this article teaches the principles that form the basis for the claimed inventions at issue, Stanford argues that the prior art, as a whole, is replete with skepticism regarding the claimed methods because the prevailing theories at the time taught that researchers should focus on proviral DNA as a surrogate marker for monitoring the effectiveness of anti-HIV treatment — not HIV RNA. Stanford has submitted scores of academic articles to this effect and the court considers the most relevant ones. First, Stanford cites to an article by Bagnarelli as a reference which allegedly teaches away from the methods taught by the patents-in-suit. Damstedt Dec., Exh. 19 (hereinafter “Bagnerelli”). Bagnerelli, which was published after the 1991 JID article, does not attempt to quantify HIV RNA, id. at 93-94, nor does it teach that measuring RNA would not be useful in monitoring drug therapy efficacy, id. at 89. The article teaches simply that reverse-transcription PCR may be used to detect HIV-1. Second, Stanford cites to an article by Fauci as evidence that the prevailing theory in 1991 taught that proviral DNA, not RNA, was the proper marker for monitoring HIV levels. Damstedt Dec., Exh. 9 (hereinafter “Fauci”). Fauci teaches that: Previous studies using in-situ hybridization techniques to detect cells expressing viral mRNA and immunofl-uorescence to detect cells expressing viral proteins have shown a low frequency of circulating lymphocytes expressing viral RNA or protein in HIV-infected individuals.... Because of the possibility that a larger proportion of cells may be latently infected, that is, containing proviral DNA but not expressing viral mRNA or protein, it was necessary to use methods sensitive enough to detect HIV proviral DNA. Id. at 681. Indeed, this article focuses on a number of potential surrogate markers and the relationship between infection and drug therapy, none of which include HIV RNA. Id. Third, Stanford cites to an article by Ottmann as proof that persons of ordinary skill in the art did not expect HIV RNA to be a viable surrogate marker for drug efficacy. Damstedt Dec., Exh. 21 (hereinafter “Ottmann”). In this reference, Ott-mann investigated a PCR-plus-reverse transcription method of detecting HIV-1 RNA without nucleic acid extraction. The detection of HIV-1 RNA resulted in no discernible difference between untreated patients and patients treated with zidovu-dine (“AZT”) — a reverse transcriptase inhibitor. Id. at 273. Although this study arguably suggests that RNA was not a proper marker for disease progression since almost all HIV-infected patients had detectable levels of RNA, the study was aimed primarily at HIV detection, not quantification. As further evidence that the prevailing theory taught that proviral DNA was the proper marker for monitoring HIV levels, Stanford and its experts point to the work of Cetus’ scientists, which focused on HIV DNA throughout this period. Stanford points to U.S. Patent Nos. 5,008,182 (“'182 patent”) and 5,389,512 (“'512 patent”), both invented by Cetus scientists Sninsky and Kwok and which issued, respectively, on April 16, 1991 and February 14, 1995. Damstedt Dec., Exhs. 12, 49. The '182 patent discloses that viral particles, such as HIV RNA, may be ah insufficient means of detecting the virus. '182 patent at 1:52-63. The '512 patent teaches a method of determining the viral load in a patient sample, where viral load is defined as copies of viral genome per cell. '512 patent at 3:14-16. This definition necessarily excludes HIV RNA in plasma as a means of determining viral load. In its analysis, Stanford fails to note that two Cetus references acknowledge the potential for HIV RNA as a marker. First, an article written by Sninsky acknowledges the potential for RNA to serve as a template for PCR. Damstedt Dec., Exh. 51. The article states: Single- and double-stranded DNA serve as effective templates for amplification. With the addition of an intervening reverse-transcription step, single- or double-stranded RNA can also serve as a template for PCR.... If RNA is the desired template, plasmid vectors capable of in vitro production of transcribed RNA are useful. Id. at 94. This article explicitly contemplates the use of RNA as a template for PCR, though not specifically in the HIV context. Second, an article co-written by Sninsky and Kwok acknowledges that the PCR procedure has been applied to HIV RNA, and that such a procedure may be a productive area of research to monitor mRNAs. Damstedt Dec., Exh. II. There are three other prior art references worth noting. First, an article by Ho discloses methods of measuring the levels of HIV-1 in cells and plasma using virus cultures — not PCR. Damstedt Dec., Exh. 15 (hereinafter “Ho”). This reference shows that HIV-1 virus was found in the plasma and PBMC of every seroposi-tive HIV patient. In essence, this test found that titers of virus in plasma were a useful marker since the number of titers were higher in patients with more advanced disease. Id. at 1622. This reference also disclosed that short-term AZT therapy decreased HIV-1 levels in plasma, id. at 1621-22, and long-term AZT therapy showed significantly decreased plasma titers, id. at 1622. Second, an article by Coombs similarly discloses methods of correlating plasma viremia with the stage of HIV infection using virus cultures — not PCR. Demstadt Dec., Exh. 17 (hereinafter “Coombs”). Coombs disclosed that among the four vi-rologic markers of HIV infection he evaluated, plasma viremia was the best indicator of clinical disease progression. Id. at 1629. However, Combs discloses a wide range of plasma HIV titers among patients with similar illness progression. Id. Third, the 1990 State-of-the-Art Conference Report disclosed that “there is no laboratory marker other than the CD4 count that is necessary in deciding when to initiate zidovudine therapy.” Damstedt Dec., Exh. 24 at 341 (hereinafter “1990 State-of-the-Art Report”). The Report concluded that “further research is needed on the use of CD4 lymphocyte counts and other immunologic markers for the initiation of therapy and the management of patients. Each of these markers can be subject to considerable variability within individual patients.” Id. at 343. In sum, the prior art includes references that disclose: 1) methods of detecting and quantifying HIV RNA in patient serum using PCR; 2) methods of monitoring the status of the infection and drug efficacy that fail to contemplate HIV RNA as a possibility; 3) notations regarding the problematic nature of surrogate markers associated with circulating virus; and 4) notations regarding a lack of a discernible difference between the detection of HIV RNA in treated and untreated patients. While this survey of the scope and content of the prior art is necessarily limited to a subset of the myriad references submitted by the parties, the remaining references serve merely to corroborate the discordance amongst those skilled in the art at the time the patents were issued. The only thing that is clear from the library of references submitted by the parties is that HIV research — particularly quantification using PCR and identification of surrogate markers — was in a state of uncertainty. B. Differences Between the Prior Art and the Claims at Issue The second Graham factor examines the differences between the prior art and the claims at issue. When surveying the differences between the prior art and the claims at issue, “section 103 specifically requires consideration of the claimed invention as a whole.” Princeton Biochems., 411 F.3d at 1337 (internal quotations omitted); see also W.L. Gore & Assocs., Inc. v. Garlock, Inc., 721 F.2d 1540, 1548-51 (Fed. Cir.1983) (“Each claimed invention must be considered as a whole.... Claims 3 and 19 must be considered individually and separately.”). The ‘as a whole’ instruction in title 35 prevents evaluation of the invention part by part. Without this important requirement, an obviousness assessment might successfully break an invention into its component parts, then find a prior art reference corresponding to each component. This line of reasoning would import hindsight into the obviousness determination by using the invention as a roadmap to find its prior art components. Further, this improper method would discount the value of combining various existing features or principles in a new way to achieve a new result-often the essence of invention. Princeton Biochems., 411 F.3d at 1337 (internal quotations and citations omitted). Roche asserts that the JID article differs from the asserted patents only to the extent that the patent claims teach the use of the prior art PCR assay on patients receiving drug therapy in order to determine therapeutic effectiveness. While the prior art does disclose the use of the PCR assay for quantifying and detecting HIV RNA, the prior art does not disclose the specific correlation limitations disclosed in the asserted patents. See, e.g., 730 patent, claims 7-9, 13, 14, 19, 23; '705 patent, claims 9-10; '041 patent, claims 2-3. In fact, none of the prior art references disclose specific information that would lead to the conclusion that quantifying levels of HIV RNA in patient plasma could be correlated with the efficacy of drug therapy. Speculation to this effect is suggested in some of the references, see JID article, supra note 2, at 865 (“Serum PCR may provide an additional marker of disease progression and drug efficacy that could improve our ability to monitor the course of HIV infection. Further studies will be necessary to validate this approach.”); Bagnerelli, supra note 3, at 89 (“although this qualitative laboratory method may have diagnostic value, a quantitative assay for HIV-1 viremia in treated and untreated seropositive patients would probably be of greater clinical interest”); however, these statements merely suggest the necessary next steps in this field of research. Looking at each asserted claim, the differences help clarify the obviousness analysis. 1. The ' 7S0 Patent The '730 patent discloses methods of monitoring the clinical progression of HIV infection and determining antiviral drug efficacy using PCR to quantify HIV RNA as a surrogate marker. In each of the asserted claims, the collecting, amplifying, and testing — or measuring — steps are disclosed and taught by the JID article. Thus, the differences discussed in the following sections will focus on the correlations disclosed in each claim. a. Claim 1 The correlation standard of claim 1 discloses that “the absence of detectable HIV-encoding nucleic acid correlates positively with the conclusion that the antire-troviral agent is therapeutically effective.” '730 patent, claim 1 at 21:57-67, 22:56-58. No subjects of the tests disclosed in the JID article were receiving antiretroviral therapy, and as a result, the methods described in the JID article fail to evaluate the effectiveness of anti-HIV therapy. The Ho article discloses that patients undergoing AZT therapy showed a decreased HTV-titer in plasma. Yet, the claimed subject matter at issue is broader than the links disclosed in the Ho article. For instance, a protease inhibitor — as an antire-troviral agent — would be included in claim 1 of the '730 patent for evaluation of effectiveness, but the prior art fails to disclose a correlation between HIV RNA and protease inhibitor efficacy. b. Claim 5 Claim 5 discloses “[t]he method of claim 1, 2, 3, or 4 in which the antiretroviral agent is zidovudine [AZT].” '730 patent, claim 5 at 22:66-67. As previously noted, the JID article does not include data or information regarding patients receiving any anti-HIV therapy. The Ho article, however, discloses that patients undergoing AZT therapy showed a decrease in HIV-titer in plasma. c. Claim 6 The correlation standard of claim 6 discloses that “the presence of detectable HIV-encoding nucleic acid correlates positively with the conclusion that the antire-troviral agent is therapeutically ineffective.” '730 patent, claim 6 at 23:1-14. This correlation is merely the converse of that disclosed in claim 1. d. Claim 7 The correlation standard of claim 7 discloses that “the presence of detectable HIV-encoding nucleic acid correlates positively with an absolute CD4 count of less than 200 cells per cubic millimeter.” '730 patent, claim 7 at 23:15-27. The JID article considered the relationship between PCR measurement of HIV RNA and CD4, and it disclosed that “[s]erum from patients with <400 CD4 cells/mm3 was more likely to be PCR positive.” JID article, supra note 2, at 864. The authors concluded that “[t]hese findings provide evidence that the amount of cell-free virus in circulation correlates with the presence of ... CD4 counts < 400/mm3.” Id. at 865. While the standard disclosed in the claimed methods — 200 cells per cubic millimeter — is consistent with the correlation disclosed in the JID article, this specific standard is not disclosed in any of the prior art references. e. Claim 8 The correlation standard of claim 8 discloses that “the absence of detectable HIV-encoding nucleic acid correlates positively with an absolute CD4 count of greater than 200 cells per cubic millimeter.” '730 patent, claim 8 at 23:29-41. This correlation is merely the converse of that disclosed in claim 7, discussed previously. f. Claim 9 The correlation in claim 9 discloses that “an HIV RNA copy number greater than about 500 per 200 ul of plasma correlates positively with the conclusion that the an-tiretroviral agent is therapeutically ineffective.” '730 patent, claim 9 at 23:42-55. The JID article quantified HIV RNA using a relationship between absorbance and known copy number of gag gene RNA. JID article, supra note 2, at 862. It discloses HIV RNA copy numbers ranging from 100 to greater than 50,000 per 200 ul of serum from patients at differing stages of the disease. Id. Neither the specific correlation, nor the correlation standard in this claim, however, are disclosed in any prior art reference. g. Claim IS Claim 13 of the '730 patent discloses “[t]he method of claim 9, 10, 11, or 12 in which the antiretroviral agent is zidovu-dine.” '730 patent, claim 13 at 24:3-4. As discussed above, no prior art reference discloses the specific correlation disclosed in claim 9. The Ho article discloses that patients undergoing AZT therapy showed a decreased HIV-titer in plasma without correlating HIV RNA copy number, as in this claim. h. Claim H. The correlation standard in claim 14 discloses that “an HIV RNA copy number less than about 200 per 200 ul of plasma correlates positively with the conclusion that the antiretroviral agent in therapeutically effective.” '730 patent, claim 14 at 24:5-18. This standard is merely the converse of that disclosed in claim 9, discussed previously, with a different standard for the correlation. Claim 9 discloses a standard “greater than about 500 per 200 ul of plasma” as correlating with therapeutic ineffectiveness. Claim 14, however, discloses a standard “less than about 200 per 200 ul of plasma” as correlating with therapeutic effectiveness. Like claim 9, neither the specific correlation, nor the correlation standard in this claim are disclosed in any prior art reference. i. Claim 18 Claim 18 of the '730 patent discloses “[t]he method of claim 14, 15, 16, or 17 in which the antiretroviral agent is zidovu-dine.” '730 patent, claim 18 at 24:26-27. As previously noted, no prior art references disclose the specific correlation disclosed in claim 14. The Ho article discloses that patients undergoing AZT therapy showed a decreased HIV-titer in plasma, but does not correlate HIV RNA copy number, as in this claim. j.Claim 19 Claim 19 of the '730 patent discloses: A method of evaluating the effectiveness of anti-HIV therapy of a patient comprising: (i) collecting one pre-treatment plasma sample from an HIV-infected patient who is about to be treated with an antiretroviral agent; (ii) collecting a post-treatment plasma sample from the HIV-infected patient after the patient has been treated with the antiretroviral agent; (iii) amplifying the HIV-encoding nucleic acid in the pre-treatment and post-treatment plasma samples using HIV primers in about 30 cycles ofPCR; (iv) measuring the HIV RNA copy number using the products of the PCRs of step (iii); and (v) comparing the HIV RNA copy number in pre-treatment and post-treatment plasma samples, in which a ratio of HIV RNA copy number in pre-treatment and post-treatment plasma samples of greater than about 4 to 1 correlates positively with the conclusion that the anti-HIV agent is therapeutically effective. '730 patent, claim 19 at 24:28^7. This claim discloses a method of monitoring the change in HIV RNA copy number using a ratio and correlating that ratio to therapeutic effectiveness. No prior art reference discloses the method of quantifying HIV RNA over time, the ratio method of correlating, nor this specific 4 to 1 ratio for determining therapeutic effectiveness. k. Claim 23 Claim 23 of the '730 patent discloses “[t]he method of claim 19, 20, 21, or 22 in which the antiretroviral agent is zidovu-dine.” '730 patent, claim 23 at 24:56-57. As previously noted, no prior art references disclose the specific correlation disclosed in claim 19. The Ho article discloses that patients undergoing AZT therapy showed a decrease in HIV-titer in plasma, but does not correlate a ratio of pre-treatment and post-treatment HIV RNA copy numbers, as in this claim. 2. The '705 Patent Like the '730 patent, the '705 patent discloses methods of monitoring the clinical progression of HIV infection and determining antiviral drug efficacy using PCR to quantify HIV RNA as a surrogate marker. a.Claim 1 Claim 1 of the '705 patent discloses: A method of evaluating the effectiveness of anti-HIV therapy of an HIV-infected patient comprising: a) collecting statistically significant data useful for determining whether or not a decline in plasma HIV RNA copy numbers exists after initiating treatment of an HIV-infected patient with an antiretroviral agent by: (i) collecting more than one plasma sample from the HIV-infected patient at time intervals sufficient to ascertain the existence of a statistically significant decline in plasma HIV RNA copy numbers; (ii) amplifying the HIV-eneoding nucleic acid in the plasma samples using HIV primers via PCR for about 30 cycles; (iii) measuring HIV RNA copy numbers using the products of the PCR step (ii); (iv) comparing the HIV RNA copy numbers in the plasma samples collected during the treatment; and b) evaluating whether a statistically significant decline in plasma HIV RNA copy numbers exists in evaluating the effectiveness of anti-HIV therapy of a patient. '705 patent, claim 1 at 23:1-22. The JID article discloses the collecting, amplifying, and measuring steps of this claim. However, it does not disclose collecting more than one sample of plasma for comparison purposes, nor does it disclose the comparing or evaluating steps. The Ho article discloses that HIV-titer in blood decreases when undergoing AZT therapy. b. Claim 5 Claim 5 discloses “[t]he method of claim 1 in which the antiretroviral agent is zido-vudine [AZT].” '705 patent, claim 5 at 23:29-30. As previously noted, the JID article does not include data or information regarding patients receiving any anti-HIV therapy. The Ho article, however, discloses that patients undergoing AZT therapy showed a decrease in HIV-titer in plasma. c. Claim 6 Claim 6 discloses “[t]he method of claim 1, wherein the presence of a statistically significant decline in plasma HIV RNA copy number correlates positively that the antiretroviral agent is therapeutically effective.” '705 patent, claim 6 at 23:32-35. No subjects of the tests disclosed in the JID article were receiving antiretroviral therapy, and as a result, the methods described in the JID article fail to evaluate the effectiveness of anti-HIV therapy. The Ho article discloses that patients undergoing AZT therapy showed a decrease in HIV-titer in plasma. d. Claim 7 Claim 7 discloses “[t]he method of claim 1, wherein the absence of a statistically significant decline in plasma HIV RNA copy number correlates positively that the antiretroviral agent is therapeutically ineffective.” '705 patent, claim 7 at 23:36-39. This claim is merely the converse of that disclosed in claim 6. e. Claim 8 Claim 8 of the '705 patent discloses: A method of evaluating the effectiveness of anti-HIV therapy of an HIV-infected patient comprising: (i) collecting a pre-treatment plasma sample from the HIV-infected patient who is about to be treated with an antiretroviral agent; (ii) collecting a plasma sample after initiation of treatment with an antir-etroviral agent and at a time interval sufficient to ascertain the existence of a statistically significant decline in plasma HIV RNA copy numbers; (iii) amplifying the HIV-encoding nucleic acid in the plasma samples using HIV primers via PCR for about 30 cycles; (iv) measuring HIV RNA copy numbers using the products of the PCR step (iii); (v) comparing the HIV RNA copy numbers in the plasma samples collected in the pre-treatment plasma sample and the plasma sample(s) collecting after initiation of the treatment; and (vi)evaluating whether a statistically significant decline in plasma HIV RNA copy numbers exists in evaluating the effectiveness of anti-HIV therapy of a patient. '705 patent, claim 8 at 24:1-22. The JID article discloses the collecting, amplifying and measuring steps of this claim. However, it does not disclose collecting more than one sample of plasma for comparison purposes, nor does it disclose the comparing or evaluating steps. f. Claim 9 Claim 9 discloses “[t]he method of claim 8, wherein comparing the HIV RNA copy numbers of step (v) further comprises determining a ratio of HIV RNA copy numbers in the pre-treatment and the post-treatment plasma samples, wherein the ratio being greater than about 7 to 1 correlates positively with the conclusion that the antiretroviral agent is therapeutically effectiveness [sic].” '705 patent, claim 9 at 24:23-29. This claim sets forth a specific standard for therapeutic effectiveness, measured by determining a ratio of HIV RNA copy numbers from before and after anti-HIV treatment. This claim therefore adds to claim 8 a particularized standard for determining therapeutic effectiveness that is not disclosed by any prior art. g. Claim 10 Claim 10 discloses “[t]he method of claim 7, wherein comparing the HIV RNA copy numbers of step (v) further comprises determining a ratio of HIV RNA copy numbers in the pre-treatment and the post-treatment plasma samples, wherein the ratio being greater than about 4 to 1 correlates positively with the conclusion that the antiretroviral agent is therapeutically effectiveness [sic].” '705 patent, claim 9 at 24:23-29. This claim is identical to claim 9, with merely a different correlation standard. 3. The 'Oil Patent Like the '730 and '705 patents, the '041 patent discloses methods of monitoring the clinical progression of HIV infection and determining antiviral drug efficacy using PCR to quantify HIV RNA as a surrogate marker. a.Claim 1 A method of evaluating the effectiveness of anti-HIV therapy of a patient comprising: correlating the presence or absence of detectable HIV-encoding nucleic acid in a plasma sample of an HIV infected patient with an absolute CD4 count, wherein the presence or absence of said detectable HIV-encoding nucleic acid is determined by (i) collecting a plasma sam pies [sic] from the HIV-infected patient who is being treated with an antiretrovi-ral agent; (ii) amplifying the HIV-encoding nucleic acid that may be present in the plasma sample using HIV primers via PCR; and (iii) testing for the presence of HIV-encoding nucleic acid sequence in the product of the PCR. '041 patent, claim 1 at 23:22-37. This method is substantially similar to that disclosed in claims 7 and 8 of the '730 patent. This claim, however, lacks the 30 cycles of amplification limitation and the specific standards set forth in claims 7 and 8 of the '730 patent. As noted previously, with respect to those two claims, the JID article considered the relationship between PCR measurement of HIV RNA and CD4, and it disclosed that “[s]erum from patients with <400 CD4 cells/mm3 was more likely to be PCR positive.” JID article, supra note 2, at 864. The authors concluded that “[t]hese findings provide evidence that the amount of cell-free virus in circulation correlates with the presence of ... CD4 counts < 400/mm3.” Id. at 865. b. Claim 2 Claim 2 discloses, “[t]he method of claim 1, wherein the absence of HIV-encoding nucleic acid and the absolute CD4 count being greater than about 200 cells per cubic millimeter correlate positively with the conclusion that the antiretroviral agent is therapeutically effective.” '041 patent, claim 2 at 23:38-42. This method is substantially similar to that disclosed in claim 8 of the '730 patent, except this claim is structured in a different manner. The substance of the methods taught, however, is virtually identical. c. Claim 3 Claim 3 discloses, “[t]he method of claim 1, wherein the presence of HIV-encoding nucleic acid and the absolute CD4 count being less than about 200 cells per cubic millimeter correlate positively with the conclusion that the antiretroviral agent is therapeutically ineffective.” '041 patent, claim 3 at 24:23-27. This claim is merely the converse of that disclosed in claim 2. It also discloses a method that is substantially similar to claim 7 of the '730 patent. While the standard disclosed in this claim — -a CD4 count of less than 200 cells per cubic millimeter — is consistent with the correlation disclosed in the JID article, this specific standard is not disclosed in any of the prior art references. d. Claim i Claim 4 discloses, “[t]he method of any one of claims 1-3, wherein the PCR is performed for about 30 cycles.” '041 patent, claim 4 at 24:28-29. Like claims 7 and 8 of the '730 patent, the steps of this claim are disclosed in the JID article, with the exception of the CD4/HIV RNA correlation set forth in claims 2 and 3, discussed above. This claim adds the “about 30 cycles” of PCR limitation, and therefore the differences between the prior art and this claim are identical to the differences between claims 7 or 8 of the '730 patent and the prior art. e. Claim 8 Claim 8 discloses “[t]he method of any one of claims 1-3 in which the antiretrovi-ral agent is zidovudine [AZT].” '041 patent, claim 8 at 24:38-39. This claim merely adds to the claimed methods standards for evaluating the efficacy of AZT therapy. The JID article discloses the collecting, amplifying, and testing steps, and as previously discussed, the Ho article teaches that effective AZT therapy results in a decrease in HIV-titer in plasma. C. Level of Ordinary Skill in the Arb With respect to the third Graham factor, this court has previously defined a person having ordinary skill in the art in this action as, “[a] medical doctor working on clinical HIV research involving antire-troviral agents or a Ph.D. researcher working on molecular methods relating to clinical HIV research involving antiretrovi-ral agents. Any person of ordinary skill in the art must have conducted numerous PCR assays in conjunction with his research.” Docket No. 212 at 7. D. Secondary Considerations The fourth and final factor in the Graham obviousness inquiry directs the court to look at objective evidence of non-obviousness — secondary considerations. 383 U.S. 1, 86 S.Ct. 684, 15 L.Ed.2d 545. In KSR, the Supreme Court noted that, “Graham set forth a broad inquiry and invited courts, where appropriate, to look at any secondary considerations that would prove instructive.” 127 S.Ct. at 1739 ((“Such secondary considerations as commercial success, long felt but unsolved needs, failure of others, etc., might be utilized to give light to the circumstances surrounding the origin of the subject matter sought to be patented.”) (quoting Graham, 383 U.S. at 17-18, 86 S.Ct. 684)). Secondary considerations do not control the obviousness inquiry, Richardson-Vicks v. Upjohn Co., 122 F.3d 1476, 1483 (Fed.Cir.1997), but they assist the court in evaluating objective indicia of non-obviousness. See Friskit, Inc. v. RealNetworks, Inc., 499 F.Supp.2d 1145, 1153-54 (N.D.Cal.2007) (Schwarzer, J.) (“secondary considerations are but part of the totality of the evidence that is used to reach the ultimate conclusion of obviousness”). 1. Commercial Success The National Institute of Health (“NIH”) publishes guidelines for the treatment of AIDS/HIV which are regularly updated by experts in the field. The latest guidelines for antiretroviral treatment prescribe a plasma HIV RNA laboratory test during the initial patient visit and state that “viral load is critical for evaluating response to therapy.” Cf. Damstedt Dec., Exh. 41. Similarly, the International AIDS Society published Recommendations for Treatment of Adult HIV Infection in 2006 which mirror this conclusion. These guidelines also provide for regular HIV RNA screening: The aim of antiretroviral therapy remains the maintenance of the plasma HIV-1 RNA level below the limits of detection of the most sensitive assays commercially available.... After 48 weeks, measures of HIV-1 RNA should be obtained at regular intervals (eg, every [sic] 3 or 4 monthly) to confirm that the plasma HIV-1 RNA level remains below the limits of detection. Cf. id., Exh. 44 at 831-32. Both of these sources — in providing general guidance to practitioners — confirm the success of the patented inventions. The patented invention claims a method of viral load testing which correlates the presence of detectable HIV RNA to therapeutic effectiveness, and both of these guidelines for practitioners specifically state that maintaining HIV RNA levels below detectable limits is desirable for effective drug therapy. The former theory, however, was effectively disclosed in the JID article. Indeed, the JID article suggested further testing of HIV RNA as a possible surrogate marker. The latter theory — minimizing the level of the surrogate marker is desirable — would be clear to one of ordinary skill in the art. Consequently, to the extent that this factor plays a part in the analysis, it hinges upon the choice of HIV RNA as the surrogate marker. This is because the remaining differences between the patent claims and the prior art — specifically the correlations disclosed in the claims — cannot be specifically linked to any commercial success. 2. Long Felt but Unsolved Need and Failure of Others In the early 1990s, NIH and the National Institute of Allergy and Infectious Diseases (“NIAID”) sponsored State-of-the-Art conferences on AZT therapy. The 1990 State-of-the-Art Conference Report stated that “there is no laboratory marker other than the CD4 count that is necessary in deciding when to initiate zidovudine therapy,” and it concluded that “further research is needed on the use of CD4 lymphocyte counts and other immunologic markers for the initiation of therapy and the management of patients. Each of these markers can be subject to considerable variability within individual patients.” 1990 State-of-the-Art Report, supra note 12, at 341, 343. The 1993 State-of-the-Art Conference Report added: [[laboratory parameters suggestive of progression would include rapidly declining CD4 + cell counts (or percentages) or [other non-HIV RNA counts]. More sophisticated assays, such as those that detect ... [other markers including] increased quantitative viral load in serum or tissue ... may become useful in the future for detecting disease progression. Damstedt Dec., Exh. 25 at 2587. These references show that amidst the uncertainty in this field, even after the publication of the JID article it was not clear to persons of ordinary skill that HIV-RNA was a proper marker. See also id., Exh. 26. However, the JID article did suggest that HIV-RNA could be a proper marker and that further research was necessary to confirm the same. Stanford also cites to the AIDS/HIV Reference Guide for Medical Professionals published in 1997, which discusses PCR techniques for detecting and quantifying DNA and RNA. A promising area of research for early diagnosis and for quantitation of HIV involves detection and quantitation of HIV nucleic acid (RNA or DNA) sequences by gene amplification techniques, such as PCR.... Much of viral RNA is defective and nonpathogenic and, thus may not reflect infectious virus production, which poses problems in evaluating its measurements. Assays using PCR ... methods were developed as used for measurement of HIV RNA in plasma (19). Several studies have demonstrated an association between levels of plasma RNA and stage of HIV disease and clinical progression. However, there are still unresolved issues such as the effect of the biological variability, the variability of reverse transcription step, the effect of processing and storage condition on genomic RNA stability, etc. At this time, a standardized quantitative RNA PCR assay is not available. Damstedt Dec., Exh. 16 at 86-87. This study recognizes that even though HIV RNA poses certain problems, it could be used as a potential surrogate marker. However, even as late as 1997, professionals working in this field were explicating a need for a “standardized quantitative RNA PCR assay” and referring to this technology only as a “promising area of research.” Id. These references, collectively, show that long after the application for the patents-in-suit had been made, researchers and practitioners were still expressing a need for a solution to the problem which the asserted patents purport to solve. This long felt need, however, was only for a proper surrogate marker to monitor therapy. Consequently, to the extent that this factor plays a part in the obviousness analysis, its focus is on the choice of HIV RNA as a surrogate marker. Because there exist no genuine issues of material fact — as outlined in this section — the court will now discuss the validity of the patents-in-suit. II. Invalidity Based on Obviousness As previously discussed, the Supreme Court recently reiterated the framework for courts to use in an obviousness analysis in KSR, 127 S.Ct. 1727. The Court reaffirmed Graham and elaborated that “[t]he combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results,” id. at 1739, and “when the prior art teaches away from combining certain known elements, discovery of a successful means of combining them is more likely to be nonobvious,” id. at 1740. Finally, the Court acknowledged that courts should be aware of the bias of hindsight because the genius of invention is often a combination of known elements, which in hindsight seems self-evident. Id. at 1742. After KSR, the United States Patent and Trademark Office (“USPTO”) published new guidelines to assist patent examiners in determining whether a claimed invention is obvious. Examination Guidelines for Determining Obviousness Under 35 U.S.C. 103 in View of the Supreme Court Decision in KSR International Co. v. Teleflex Inc., 72 Fed.Reg. 57526-01 (Oct. 10, 2007). These guidelines establish seven rationales under KSR which justify a finding of obviousness: (A) Combining prior art elements according to known methods to yield predictable results; (B) Simple substitution of one known element for another to obtain predictable results; (C) Use of known technique to improve similar devices (methods, or products) in the same way; (D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results; (E) “Obvious to try” — choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success; (F) Known work in one field of endeav- or may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations would have been predictable to one of ordinary skill in the art; (G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention. Id. at 57529. Here, when considering both the prior art references and the claimed inventions as a whole, the focus of the obviousness inquiry is directed at two portions of the claimed inventions: 1) the use of HIV RNA as a surrogate marker for drug efficacy; and 2) the correlations that use HIV RNA as a surrogate marker for drug efficacy. Each of the asserted claims is similar in that all disclose the use of HIV RNA as a surrogate marker for drug efficacy, yet all differ in that each discloses a unique correlation for evaluating drug efficacy. A. The Use of HIV RNA As a Surrogate Marker 1. Improper Focus Stanford argues that the choice to use HIV RNA in plasma as a potential surrogate marker was not obvious. This argument, however, focuses on a preliminary matter in the research methodology that resulted in the patents-in-suit. Stanford vehemently asserts that when Holodniy began focusing on HIV RNA as a surrogate marker, others skilled in the art were looking at, inter alia, DNA, CD4, and p24 antigens. See, e.g., Fauci, supra note 4 (listing numerous options for further research into potential surrogate markers, but failing to consider HIV RNA in plasma). Stanford also argues that in addition to the prevalent focus on other potential surrogate markers, particular skepticism surrounded the use of HIV RNA in plasma for this purpose. Thus, it argues the use of HIV RNA in plasma as a surrogate marker was non-obvious. Even assuming the Stanford scientists were defying prevailing wisdom by choosing to study HIV RNA in plasma as a potential surrogate marker, this choice is not explicitly embodied in the patents-in-suit, nor did it immediately result in the patents-in-suit. After the choice was made to research HIV RNA in plasma as a potential surrogate marker, Stanford scientists still had to complete a number of subsequent steps before the claimed methods were reduced to practice — the choice to use HIV RNA was therefore merely a preliminary choice on the route to developing methods to evaluate therapy efficacy. Subsequent to the choice to focus on HIV RNA, Stanford scientists went on to: 1) quantify HIV RNA in plasma, as disclosed in the JID article; 2) correlate the results of the quantitation with then-currently detectable indications of disease progression; 3) further correlate the results of the quantitation with then-currently detectable indications of drug efficacy; and 4) evaluate the utility of the correlations. The patents-in-suit incorporate all four of the above steps. Unlike Takeda Chem. Indus., Ltd. v. Alphapharm Pty, Ltd., 492 F.3d 1350 (Fed.Cir.2007), where the asserted patents claimed a genus and particular pharmaceutical chemical compounds, the claims in the instant action are method claims. The researchers there were making cognizant modifications to known compounds “in order to improve the antidiabetic activity and obtain a compound with better activity.” Id. at 1357. The Federal Circuit in Take-da discussed the options available to the researchers at the time the claimed compounds were invented when determining whether the claimed compounds were obvious. In determining that the claimed compounds were non-obvious, the court explained that “one of ordinary skill in the art would have chosen one of the [over ninety] compounds disclosed in [the prior art] ... rather than to choose as a starting point a compound with identified adverse effects.” Id. at 1360 (internal quotations omitted). Thus, in Takeda, the choice to commence research into the particular compounds which led to the patents-in-suit was a determinative factor in the obviousness analysis. There the patents-in-suit directly related to the choice of a particular compound as a starting point. Id. Here, however, the choice to research HIV RNA as a potential marker was merely a preliminary step which led, ultimately, to the claimed methods in the instant action. The choice of HIV RNA as a surrogate marker is not what was patented. Consequently, this choice is not determinative in the obviousness analysis. Common sense, along with coherence under the penumbra of patent law, dictate this result. It is clear that if Stanford had patented the five-step method of quantifying HIV RNA that is specifically disclosed in the JID article, it would have been anticipated by the prior art. No analysis regarding the state of the art at the time would have been necessary. However, if any changes — even obvious ones — are made to the process contemplated by the JID article, the analysis shifts to one of obviousness, not anticipation. Consequently, under Graham and KSR, this court is required to analyze the scope and content of the prior art, an analysis wholly missing under the anticipation rubric. This prompts the question: can a purported inventor add an obvious limitation to a piece of prior art in order to secure a method patent and then claim that because his choice of selecting the particular piece of prior art was non-obvious, the patent cannot be invalid as obvious? This cannot be so. Unless the selection process is somehow incorporated into the patent claims, the claims must be viewed independently of the selection process. The proper focus for the obviousness inquiry is on the language of the claims— which do not discuss the choice of HIV RNA as a surrogate marker. The claims define the scope of the patented invention, and the claims disclose methods of quantifying HIV RNA and using the results to evaluate drug efficacy. As discussed below, even if the choice to use HIV RNA as a marker is non-obvious, the court must nevertheless evaluate the claim language. However, before addressing the obviousness inquiry in this manner, the court disposes of Stanford’s arguments. 2. Obviousness of Choosing HLV RNA as a Surrogate Marker If Stanford is correct in its contention that its choice of using HIV RNA as a surrogate marker is an implicit claim limitation, then the obviousness or non-obviousness of this choice must be analyzed. Roche argues that Pfizer, Inc. v. Apotex, 480 F.3d 1348 (2007), renders the selection of HIV RNA as a marker to be obvious. There, the Federal Circuit held that “a skilled artisan would have had a reasonable expectation of success with the besy-late salt form of amlodipine at the time the invention was made” and therefore the particular patented salt at issue would have been obvious to try. Id. at 1368. The court found that “on the particularized facts of this case, consideration of the routine testing performed by Pfizer is appropriate because the prior art provided not only the means of creating acid addition salts but also predicted the results, which Pfizer merely had to verify through routine testing.” Id. at 1367 (emphasis added). Unlike Pfizer, however, the JID article provided no predictions to persons skilled in the art regarding the success of HIV RNA as a surrogate marker for evaluating drug efficacy. Similarly, PharmaStem Therapeutics, Inc. v. ViaCell, Inc., 491 F.3d 1342 (Fed.Cir.2007), does not aid Roche. That court found that “[scientific confirmation of what was already believed to be true may be a valuable contribution, but it does not give rise to a patentable invention.” Id. at 1363-64. However, in that case, the “joint specification indicate[d] that each step of the cryopreservation and transplantation procedure had been spelled out in the pri- or art.” Id. That is not the case here. HIV RNA was not believed to be a proper marker, nor was each step disclosed in the patents-in-suit spelled out in the prior art. PharmaStem, however, did elucidate the obviousness analysis. It found that: obviousness does not require absolute predictability of success. Indeed, for many inventions that seem quite obvious, there is no absolute predictability of success until the invention is reduced to practice. On the other hand ... an invention would not be invalid for obviousness if the inventor would have been motivated to vary all parameters or try each of numerous possible choices until one possibly arrived at a successful result, where the prior art gave either no indication of which parameters were critical or no direction as to which of many possible choices is likely to be successful. Likewise, an invention would not be deemed obvious if all that was suggested was to explore a new technology or general approach that seemed to be a promising field of experimentation, where the prior art gave only general guidance as to the particular form of the claimed invention or how to achieve it. Id. (internal quotations and citations omitted). This case is not one in which “the prior art gave either no indication of which parameters were critical or no direction as to which of many possible choices is likely to be successful,” nor is it one in which the prior art “gave only general guidance as to the particular form of the invention or how to achieve it.” The JID article specifically pointed scientists toward a possible solution — using HIV RNA as a potential marker — in a field where only a limited num