UNIVERSITY OF SOUTH FLORIDA BOARD OF TRUSTEES v. USA

MOTION for Partial Summary Judgment Claims 7,8,10 and 11 Are Not Invalid

Fed. Cl.November 5, 2018

THE UNITED STATES COURT OF FEDERAL CLAIMS UNIVERSITY OF SOUTH FLORIDA, BOARD OF TRUSTEES, Plaintiff, v. THE UNITED STATES OF AMERICA, Defendant. ) ) ) ) ) ) ) ) ) ) No. 15-1549 Judge Campbell-Smith MOTION BY USF FOR PARTIAL SUMMARY JUDGMENT – CLAIMS 7, 8, 10 and 11 ARE NOT INVALID UNDER 35 U.S.C. §112 Plaintiff University of South Florida, Board of Trustees, (hereinafter “USF”) hereby moves for entry of partial summary judgment that Claims 7, 8, 10 and 11 of the patent-in-suit, U.S. Patent No. 5,898,094 (hereinafter “the ‘094 Patent”)(Ex. 10) are not invalid by reason of failure to satisfy the written description and enabling disclosure requirement of 35 U.S.C. §112, first paragraph.1 The United States takes the position that these four claims are invalid under 35 U.S.C. §112, arguing they do not meet either the written description requirement or enablement requirement of 35 U.S.C. §112. (Defendant’s Final Invalidity Contentions, Docket 106, pp. 17–21.) Both legal arguments are tied to a single mistaken allegation repeatedly asserted by Defendant: Here the specification discloses only one particular presenilin mutation to be paired with APPswe: a presenilin-1 protein that has a 1 The ‘094 Patent (Ex. 10) issued April 27, 1999 and is thus subject to the pre-AIA statutory requirements. Case 1:15-cv-01549-PEC Document 116 Filed 11/05/18 Page 1 of 20 2 point mutation at amino acid 146, a substitution of leucine for methionine (the “M146L” mutation). (Invalidity assertions, p. 18). Respectfully, the United States repeatedly confuses the Specification disclosure with its enabling example – while one complete example is set forth and another described, in fact, as the expert retained by the government and Jackson Laboratories testified, the ‘094 Patent Specification expressly identifies thirty-two presenilin mutations that may be used in the invention! While the question of whether a disclosure of two presenilin mutations would satisfy the written description and enablement requirements of the statute for Claims 7, 8, 10 and 11 of the ‘094 Patent (Ex. 10) may be argued, no such argument is required. The ‘094 Patent (Ex. 10) sets forth thirty-two presenilin mutations that satisfy the requirements of those claims. Moreover – the twenty- two years since the filing of the ‘094 Patent (Ex. 10) have demonstrated that the single example of the ‘094 Patent (Ex. 10) in fact works for every known presenilin mutation. Given the details provided by the inventors in the specification, there is no uncertainty or question – substituting any of the thirty-two presenilin mutations described in the ‘094 Patent (Ex. 10), or indeed, any of the more than 200 presenilin mutations that have been discovered to date, gives the same positive result – a mouse expressing the APPswe mutation and any presenilin mutation will exhibit accelerated Alzheimer’s Disease pathology, as reflected in Case 1:15-cv-01549-PEC Document 116 Filed 11/05/18 Page 2 of 20 3 the enabling example of the ‘094 Patent (Ex. 10) and called for by Claims 7, 8, 10 and 11. Correctly read, there is no question of material fact that the ‘094 Patent specification sets forth multiple species of the presenilin mutation called for by the claims, and provides an enabling example instructing the reader on how to practice the claims with those mutations. Such a disclosure satisfies the written description and enabling disclosure requirements with respect to the presenilin mutation requirement of Claims 7, 8, 10 and 11. Contrary to the Government’s contentions, summary judgment that those claims are NOT invalid under 35 U.S.C. §112, first paragraph, is appropriate. This Motion is supported by a Statement of Material Facts, below, followed by an explanation as to why USF is entitled to judgment as a matter of law. Reference is made to deposition transcripts, as well as Exhibits of patents and articles. By agreement, the parties have submitted the full transcripts of the depositions of witnesses taken during fact discovery – who are referred to by their initials herein. These witnesses are; Karen Duff (hereinafter “KD”)(Ex. 1); David Borchelt (hereinafter “DB”)(Ex. 2); Marcia Gordon (hereinafter “MG”)(Ex. 4); David Morgan (hereinafter “DM”)(Ex. 5); Stephen Snyder (hereinafter “SS”)(Ex. 3) and Sangram Sisodia (hereinafter “SNS”)(Ex. 6). The exhibits that are specific to this Motion are referenced as (Ex. 10) (the ‘094 Patent) and (Ex. 12) (an article by Cruts et al). These exhibits (The Record on Summary Judgment) were Case 1:15-cv-01549-PEC Document 116 Filed 11/05/18 Page 3 of 20 4 submitted by USF as attachments to a paper entitled USF’s Motion Submitting the Record for Summary Judgment Motions on November 5, 2018. The exhibits may be used in reference to all summary judgment motions filed by USF as well as any that may be filed by the United States. I. STATEMENT OF MATERIAL FACTS NOT IN DISPUTE USF advances a series of statements of material fact as to which there cannot be any dispute. These material facts are separated into two sections addressing each of the arguments advanced by the United States in support of its position that Claims 7, 8, 10 and 11 of the ‘094 Patent (Ex. 10) are invalid under the written description and enabling disclosure requirements of 35 U.S.C. § 112. These statements of material fact are supported by citations to the record. This Motion refers to the Depositions of David Borchelt, a researcher in the field at the time (hereinafter “DB”) (Ex. 2); Karen Duff , an inventor (hereinafter “KD”)(Ex. 1); and Sangram Sisodia, a colleague of Borchelt’s and expert witness retained by the United States and the Jackson Laboratories (hereinafter “SNS”)(Ex. 6). In addition, Plaintiff relies on exhibits specific to this Motion, including the ‘094 Patent (Ex. 10), and Cruts et al, Human Molecular Genetics, 5:1449–1455 (1966) (Ex. 12). A. The ‘094 Patent Discloses Multiple Presenilin Transgenes 1. At Col. 7, ll. 16–18 of the ‘094 Patent (Ex. 10), in a section entitled Detailed Description of the Preferred Embodiment, the patent recites: “In a Case 1:15-cv-01549-PEC Document 116 Filed 11/05/18 Page 4 of 20 5 preferred embodiment for a model of AD (sic, Alzheimer’s Disease) the first parental animal carries an expressible transgene for a mutant presenilin transgene [Cruts et al., 1996; Duff et al, 1996 (Ex. 12)].” Ex. 10, Col. 7, ll.16–18. 2. In the same section of the ‘094 Patent (Ex. 10), twenty lines further in, the ‘094 Patent (Ex. 10) discusses the presenilin mutations against the backdrop of the enabling example set forth at Col. 8, l. 34 – Col. 12, l. 20. At Ex. 10, Col. 7, ll. 38–42, the Specification instructs the reader: Any human presenilin or amyloid precursor protein gene or subsequently discovered homologs can be used…”. Ex. 10, Col. 7, ll. 38–40. 3. The full citation to the Cruts et al 1996 paper (Ex. 12) referred to at Col. 7 is set forth in the ‘094 Patent (Ex. 10) at Col. 12, ll. 44–46: Cruts et al, 1996, “The Presenilin Genes – A Gene Family Involved in Alzheimer’s Disease Pathology,” Human Molecular Genetics, 5 (Review);1449–1455. Ex. 10, Col. 12, ll. 44–46. 4. The ‘094 Patent (Ex. 10), just before the full citation for all the references are set forth, makes the following specific statement: “Full citations for the publications are listed below. The disclosures of these publications and patents are hereby incorporated by reference into this application in order to more fully describe the state of the art to which this invention pertains.” (Emphasis supplied). Ex. 10, Col. 11, ll. 40–44. Case 1:15-cv-01549-PEC Document 116 Filed 11/05/18 Page 5 of 20 6 5. The expert witness retained by The Jackson Labs and the United States, Sangram Sisodia, initially presented a declaration sworn to under the penalties of perjury that asserted at the time of filing the ‘094 Patent (Ex. 10) in July of 1997, there were only ten presenilin mutations known in the art. When confronted with the Cruts paper (Ex. 12) referenced in the ‘094 Patent (Ex. 10) and incorporated by reference, Sisodia testified that Cruts was right, there were at least 32 presenilin mutations known to those of skill in the art by July 1997. SNS (Ex. 6) 85:19–86:11. 6. All presenilin mutations, when expressed in a mouse also expressing the APPswe mutation, demonstrate an acceleration of Alzheimer’s Disease pathology. DB (Ex. 2) 68: 11–70:2; KD (Ex. 1) 81:12–82:9. 7. Karen Duff wrote the USF application which was then “legalized” by an attorney for USF. KD (Ex. 1) 75:13–76:12. 8. Duff testified that she did not include a specific listing of each suitable presenilin mutation for use in the dually transgenic mice of the ‘094 Patent (Ex. 10) because it was assumed that all presinilin mutations would act in the same fashion. KD (Ex. 1) 67:10–20. 9. Crossbreeding a mouse that expresses the APPswe mutation with one expressing any presinilin mutation pursuant to the Example and Specification of the ‘094 Patent (Ex. 10) results in mice that actually exhibit acceleration of Case 1:15-cv-01549-PEC Document 116 Filed 11/05/18 Page 6 of 20 7 Alzheimer’s Disease pathology like accelerated brain deposition of Aß-42. DB (Ex. 2) 90:14–18. 10. Stephen Snyder, program administrator for NIH and the witness of the United States responsive to issues involving funding of research by NIH, selected David Borchelt to review an NIH grant application that proposed funding for work to make the doubly transgenic mice of the ‘094 Patent (Ex. 10) because Borchelt was working in the same field in 1995– 1996 and had a good understanding of the technology. (“Dave Borchelt, with his background, was really an ideal candidate as a reviewer”). SS (Ex. 3) 40:29–43:19. 11. All of the presenilin mutations David Borchelt is aware of up through 2018, when co-expressed in a mouse with the APPswe mutation, accelerate Alzheimer’s Disease pathology such as amyloid deposition and plaque formation. DB (Ex. 2) 68:15–70:2. 12. The double transgenic mice made in 1996, 1997 and 1998, when made with a presenilin mutation and the Swedish mutation (APPswe) provided acceleration of amyloid deposits (Alzheimer’s Disease pathology) regardless of which presenilin mutation was used. KD (Ex. 1) 81:12–20. 13. While Karen Duff was not sure how many doubly transgenic mice had been made by 2018 using various presenilin mutations and the APPswe mutation, all of the ones she is aware of work in the same fashion to accelerate Alzheimer’s Disease pathology. KD (Ex. 1) 81:12–82:14. Case 1:15-cv-01549-PEC Document 116 Filed 11/05/18 Page 7 of 20 8 II. THE ‘094 PATENT SATISFIES THEWRITTEN DESCRIPTION REQUIREMENT FOR CLAIMS 7, 8, 10 AND 11 Fundamentally, USF respectfully submits that the arguments offered by United States to support the position that Claims 7, 8, 10 and 11 of the ‘094 Patent (Ex. 10) are not supported by an adequate written description are based on mischaracterizations of that Patent and a deliberate effort to ignore the knowledge of those of skill in the art as of July, 1997 when it was filed. The ‘094 Patent (Ex. 10) left nothing to question – after discussing possible presenilin mutations the inventors were aware of, the Patent then referred to the Cruts et al publication (Ex. 12) – subsequently “incorporating it by reference.” A publication that is specifically recited to be “incorporated by reference” in a U.S. Patent is understood to be expressly and explicitly part of the Patent Specification incorporating it. Telecordia Technologies Inc. v. Lucent Technologies, 514 F. Supp. 2d 598, 610 (D. Del. 2007) citing Advanced Display Sys., Inc. v. Kent State Univ., 212 F. 3d 1272, 1282 (Fed. Cir.2007): “Incorporation by reference provides a method for integrating material from various documents into a host document—a patent or printed publication in an anticipation determination—by citing such material in a manner that makes clear that the material is effectively part of the host document as if it were explicitly contained therein.” The Court of Appeals for the Federal Circuit reached an identical result this year citing the same case law in support of its finding that the publication in Case 1:15-cv-01549-PEC Document 116 Filed 11/05/18 Page 8 of 20 9 question was explicitly part of the host document (Patent specification) incorporating it by reference. Paice LLC v. Ford Motor Company, 881 F. 3d 894, 907 (Fed. Cir. 2018). The Court commented on the precise language used in the ‘094 Patent (Ex. 10): The first sentence of this passage is broad and unambiguous. It states that Severinsky “is,” without qualification, incorporated into the '817 application “by this reference”— i.e., the reference contained in the sentence. The sentence identifies with detailed particularity the specific material subject to incorporation (Severinsky, and not just particular portions thereof) and where that material can be found . Such language is plainly sufficient to incorporate Severinsky in its entirety. By the same operation of law, where the ‘094 Patent (Ex. 10) provides the precise citation for Cruts et al, 1996, “The Presenilin Genes – A Gene Family Involved in Alzheimer’s Disease Pathology,” Human Molecular Genetics, 5 (Review);1449– 1455 (Ex. 12) and then recites at Col. 11, ll. 41 – 45 that reference, like others, “are hereby incorporated by reference” to “more fully describe” the state of the art pertaining to the field of endeavor, such language is plainly sufficient to incorporate Cruts et al (Ex. 12) in its entirety into the ‘094 Patent (Ex. 10). In re De Seversky, 474 F. 2d 671, 674 (CCPA 1973) noting: Appellant is confusing two distinctly different things: (1) the right to have the benefit of the filing date of an earlier application under § 120 for subject matter claimed in a later application because that subject matter is disclosed in an earlier application to which “a specific reference” is made–i.e., a reference to the earlier application per se, and (2) the incorporation by reference in an application of matter elsewhere written down (not necessarily in a patent application), for economy, amplification, or clarity of exposition, by Case 1:15-cv-01549-PEC Document 116 Filed 11/05/18 Page 9 of 20 10 means of an incorporating statement clearly identifying the subject matter which is incorporated and where it is to be found. (Emphasis supplied). Thus, as testified by Sangram Sisodia, the ‘094 Patent Specification specifically and expressly identifies not two, but thirty-two presenilin mutations satisfying the written description requirement of the claims in question which call for a “presenilin mutation.” On October 24, 2018 the Federal Circuit reviewed the written description requirement in the context of determining whether a patent application adequately describes an invention claimed in that application, the precise argument the government advances as to Claims 7, 8, 10 and 11. FWP IP APS, v. Biogen MA, Inc., 2018 WL 5292070 (Fed. Cir. 2018). The Court confirmed that where patent a specification, like that of the ‘094 Patent that is Ex. 10, specifically identifies the discrete elements to be used in the invention, such as a presenilin mutation and an APPswe mutation, rather than simply naming them in a broad group of contemplated alternatives, written description is made out. Biogen at *6 - 7. Thus, unlike the specification considered in Biogen, the ‘094 Patent specification (Ex. 10) guides one directly to the effective target – the APPswe mutation, and any presenilin mutation. Biogen at *6. To the same effect, where the prior art teaches a key limitation of the invention, like the presenilin mutations disclosed in the publication of the Cruts publication that is Ex. 12 or the APPswe mutation Case 1:15-cv-01549-PEC Document 116 Filed 11/05/18 Page 10 of 20 11 disclosed in the Hsiao publication that is Ex. 13, that prior art information enhances the disclosure of the application. Id. Ultimately, the Court found the specification in Biogen to lack written description because one of skill in the art would have to “pick and choose” from among many different contemplated limitations to arrive at the invention of the claims at issue. Biogen at *7. In contrast, the ‘094 Patent specification (Ex. 10) clearly directs those of skill in the art to combine two well-known features, specifically identifying combining an APPswe mutation-expressing mouse with any of the specific presenilin mutations of the Cruts publication, Ex. 13 identified and incorporated by reference in the ‘094 Patent specification of Ex. 10. While it is not clear whether Claims 7, 8, 10 and 11 of the ‘094 Patent (Ex. 10) would somehow lack written description of a “presenilin mutation” given the knowledge of skill in the art and the disclosure of two presenilin species2, there is no need to consider that question. Thirty-two different suitable presenilin mutations expressly recited and incorporated by reference by the ‘094 Patent (Ex. 10) is certainly adequate to describe and enable the use of those mutations. Ariad Pharmaceuticals, Inc. v. Eli Lilly and Co., 598 F.3d 1336, 1349 (Fed. Cir 2010) (en banc) (“[T]he specification must demonstrate that the applicant has made a 2 There is considerable discussion of presenilin mutations in the ‘094 Patent (Ex. 10), including 3:24–51, discussing the references to Scheuner, 1966, Duff, 1966, L’Hemault 1992 and others. This relevant prior art may be relied upon to satisfy the written description requirement. Falko–Gunter Falkner v. Inglis, 448 F.3d 1357 1366–68 (Fed.Cir.2006). Case 1:15-cv-01549-PEC Document 116 Filed 11/05/18 Page 11 of 20 12 generic invention that achieves the claimed result and do so by showing that the applicant has invented species sufficient to support a claim to the functionally- defined genus.”) There is neither case law nor logic that supports the notion that identifying thirty-two different species of “presenilin mutations” is not somehow sufficient to support a claim to the genus of those mutations. In the same way a reference to a biological deposit where specific species of the genus are set forth may satisfy the written description requirement of the statute, Enzo Biochem, Inc. v. Gen-Probe Inc. 323 F.3d 956, 965 (Fed. Cir. 2002) so may reference to a prior art disclosure which sets forth those species satisfy the legal written description provision. The notion that the specification of a patent must restate the known species of the prior art, as opposed to referring to them generically, to satisfy the requirements of 35 U.S.C. §112, first paragraph was soundly rejected in Capon v. Eshhar, 418 F.3d 1349, 1358 (Fed. Cir. 2005). III. THE TEMPLATE EXAMPLE SET FORTH IN THE ‘094 PATENT, COUPLED WITH THE DESCRIPTION OF 32 DIFFERENT PRESENILIN MUTATIONS TO CO-EXPRESS WITH THE APPSWE MUTATION, SATISIFES THE ENABLING DISCLOSURE REQUIREMENT OF 35 U.S.C. § 112 The United States presses the argument that ‘094 Patent (Ex. 10), including the very specific “template” example3 which recites the use of a specific presenilin mutation that may be substituted for by any other presenilin mutation, Col. 8, l. 34 3 A “template example” is one laid out in step by step detail, and permits at every step, such as mutation selection, substitution of a different entity for the one recited in the template. Case 1:15-cv-01549-PEC Document 116 Filed 11/05/18 Page 12 of 20 13 – Col. 12, l. 20, is not sufficient to enable the invention of Claims 7, 8, 10 and 11 because it is only one example, and one cannot predict what would happen if a different presenilin mutation were substituted for the M146L presenilin mutation of the Example. The argument is not only unsupported, but contrary to known facts not in dispute. The argument rests on the allegation that “creating a transgenic mouse with a presenilin point mutation, such that the mouse has accelerated brain deposition of Aß protein, is an empirical task which must be carried out one mutation at a time. As noted above, tiny mutations in the gene can yield substantial and unpredictable changes in the resulting protein.” (Emphasis in original). United States’ Final Contentions, p. 18 (Docket 106). In fact, that assertion is simply wrong. Hardy and Duff did not identify the effects of a single mutation and lay a claim to any other mutation. Hardy and Duff learned of the behavior of presenilin mutations (Hardy worked with Cruts et al on the paper, Ex. 12, see p. 1453 of that paper) and based on the behavior of presenilin mutations on the one hand, and the behavior of the APPswe mutation on the other, came to a logical explanation of what should happen – an explanation borne out by the results not just in some cases, but in every doubly transgenic mouse of this type made in the last twenty-two years! Rather than simply identifying a starting point for experimentation, as asserted by the United States, Contentions, Docket 106, p. 21, the inventors laid out a template for producing a mouse with accelerated Alzheimer’s Disease Case 1:15-cv-01549-PEC Document 116 Filed 11/05/18 Page 13 of 20 14 pathology, providing a detailed example in which the recited presenilin mutation could be substituted for by someone of skill in the art with any of the thirty-one others set forth in the Specification through the incorporation by reference of the article by Cruts et al (Ex. 12). Indeed, given the express language of the Specification, that same template example could be easily modified by one of skill in the art to substitute any “subsequently discovered” presenilin mutation for the M146L mutation employed in the example of the ‘094 Patent (Ex. 10). The inventors specifically taught this at Col. 7, ll. 35 – 42. Both Karen Duff, the technical author of the ‘094 Patent (Ex. 10), and David Borchelt testified that the example of the ‘094 Patent (Ex. 10) of taking a mouse expressing an APPswe transgene, such as the APPswe expressing mouse Tg2576 and cross-breeding it with a mouse expressing a presenilin mutation was successful in providing mice with accelerated Alzheimer’s Disease pathology as this Court has construed that term. They both testified that not just the specific mutations set forth in Cruts et al, (Ex. 12) and incorporated by reference into the ‘094 Patent (Ex. 10), worked to this end, but all presenilin mutations ever tested gave the claimed result. This was something foreseen by the co-inventors Hardy and Duff. That is why the ‘094 Patent (Ex. 10) embraces not only the presenilin mutations identified as of the date of filing, but all similar mutations yet to be discovered. As the ‘094 Patent (Ex. 10) expressly states: Case 1:15-cv-01549-PEC Document 116 Filed 11/05/18 Page 14 of 20 15 However, any mutant presenilin or amyloid precursor protein gene or any subsequently discovered homologs can be used that provide complementarity/interactivity for the expressed amyloid associated AD phenotype of accumulation Aß. Ex. 10, Col. 7. ll. 38– 42. (Emphasis supplied). When asked how she had been confident, in 1996, that any presenilin mutation would work, Duff replied that it was completely logical, it was an “idea we thought would happen.” KD (Ex. 1) 69:15 – 17. It is surely correct that whether or not a patent specification is enabling as to specific claims is a determination that is made as of the filing date – the specification cannot be altered by information or knowledge developed after the filing date of the ‘094 Patent (Ex. 10). The Court can, however, consider post- filing evidence that the method disclosed works independent of the identity of the presenilin mutant selected in concluding that those of ordinary skill in the art were enabled by the July, 1997 filing date to practice the invention of Claims 7, 8, 10 and 11 independent of the identity of the presenilin mutant selected. See In re Brana, 51 F.3d 1560, 1567 (Fed. Cir. 1995), Ex Parte Shyamramakrishnan, 2006 WL 3939190*at 6 (BPAI 2006), citing Gould v. Quigg, 822 F.2d 1074, 1078, (Fed. Cir. 1987). Both Duff and Borchelt testified that it just does not matter – a mouse that expresses both the APPswe mutation and a presenilin mutation, any presenilin mutation, will exhibit accelerated Alzheimer’s Disease pathology. Hardy and Duff did not arrive at their invention by looking at a single empirical point mutation, they conceived of the invention by concluding that the nature of amyloid pathology Case 1:15-cv-01549-PEC Document 116 Filed 11/05/18 Page 15 of 20 16 was such that it should work. The inventors’ insight is reflected in the following exchange between Karen Duff and counsel for the United States during her deposition at KD (Ex. 1) 88:3–89:7: Q: That was the general idea behind this? A: Yes, based on what had been observed in the human pathology and what we knew of presenilin mutations increasing A- beta. And John’s expertise in this area. Q: Okay. So the idea was you could pick any of the available APP mutations and you would probably get the same result? A: We considered it to be likely, yes. Q: And that was based on what you knew based on lines of single mutations of APP? A: John’s lab had a lot of experience in looking at APP and presenilin, so he made the prediction that that should accelerate the pathology. Q: So it’s like basically a yes to my question that – A: It’s a yes that within the lab we had a lot of insight into the disease. The invention captured in the ‘094 Patent (Ex. 10) was not a lucky empirical datum in a sea of data – it was based on the inventors’ insight given their knowledge of the physiology impacted by both the APPswe mutation and presenilin mutations. Measured by the harshest standard of all – the test of time – that insight has borne true – any presenilin mutation will accelerate the Alzheimer’s Disease pathology Case 1:15-cv-01549-PEC Document 116 Filed 11/05/18 Page 16 of 20 17 exhibited by the APPswe mutation, or a wild type mouse. While the acceleration may be more for one mutation than another, they all work. By any measure, the disclosure provided in the ‘094 Patent (Ex. 10), including the template example, and the incorporated express disclosure of thirty- two presenilin mutations any one of which may be combined with the APPswe mutation to provide for accelerated Alzheimer’s Disease pathology, is an enabling disclosure. The United States has not, and cannot, prove to the contrary. There is no material question of fact – and USF is entitled to judgment as a matter of law. Claims 7, 8, 10 and 11 of the ‘094 Patent (Ex. 10) are not invalid for lack of enablement. IV. CONCLUSION The only argument advanced by the United States to support the position that the challenged claims of the ‘094 Patent (Ex. 10) are not supported by an enabling written description and thus are invalid is that the ‘094 Patent (Ex. 10) does not provide an enabling written description of the presenilin mutations that may be used in Claims that do not specify which presenilin mutation to use, such as Claim 7. The United States argues that the ‘094 Patent (Ex. 10) fails to describe sufficient examples of a presenilin mutation such as called for in Claims 7 and 8 to adequately reflect an understanding and knowledge of the genus of “presenilin mutations”. Additionally, the United States complains there can be no enablement when there is but a single example of success in an unpredictable art. Case 1:15-cv-01549-PEC Document 116 Filed 11/05/18 Page 17 of 20 18 With respect to written description, USF notes that the ‘094 Patent (Ex. 10) specifically references abundant art pertaining to presenilin mutations that the Government did not even consider. More importantly, by expressly incorporating by reference Cruts et al, (Ex. 12) the ‘094 Patent (Ex. 10) literally and expressly includes thirty-two effective presenilin mutations, certainly sufficient to “define the genus” of presenilin mutations. The template example provided in the ‘094 Patent (Ex. 10) worked the first time, the second time, and every time it has been tried in the twenty-two (22) years since the ‘094 Patent (Ex. 10) was filed, regardless of the identity of the presenilin mutation. If you provide a mouse that expresses the APPswe transgene, and a presenilin mutation transgene – you will observe accelerated Alzheimer’s Disease pathology, as recited by the claims. Providing a universally successful template example that permits for ready substitution of one mutation for another is a clear, undeniable demonstration of enablement. There is no material question of fact that the ‘094 Patent (Ex. 10) meets the requirements of 35 U.S.C. §112, first paragraph for the subject matter claimed in Claims 7, 8, 10 and 11. Accordingly, entry of summary judgment that those claims are not invalid for lack of written description or enablement is respectfully requested. Case 1:15-cv-01549-PEC Document 116 Filed 11/05/18 Page 18 of 20 19 Respectfully submitted, Dated: November 5, 2018 OF COUNSEL: Jerry Stouck Email: stouckj@gtlaw.com GREENBERG & TRAURIG 2101 L Street, N.W., Suite 1000 Washington, DC 20037 (202) 331-3173 phone (202) 261-4751 facsimile s/Steven B. Kelber Steven B. Kelber Email: steve@kelberlawgroup.com THE KELBER LAW GROUP 1875 Eye Street, N.W., Fifth Floor Washington, D.C. 20006 240-506-6702-Telephone Counsel for Plaintiff University of South Florida, Board of Trustees Case 1:15-cv-01549-PEC Document 116 Filed 11/05/18 Page 19 of 20 20 LIST OF EXHIBITS CITED IN THIS MOTION Exhibit 1 Deposition Transcript of Karen Duff (referenced as “KD”) Exhibit 2 Deposition Transcript of David Borchelt (referenced as “DB”) Exhibit 3 Deposition Transcript of Stephen Snyder (referenced as “SS”) Exhibit 4 Deposition Transcript of Marcia Gordon (referenced as “MG”) Exhibit 5 Deposition Transcript of David Morgan (referenced as “DM”) Exhibit 6 Deposition Transcript of Sangram Sisodia (referenced as “SNS”) Exhibit 7 Declaration of William Coppola Exhibit 10 U.S. Patent No. 5,898,094, issued April 27, 1999 (“094 Patent”) Exhibit 11 U.S. Provisional Patent Application 60/028,937, filed October 21, 1996 (“’937 Application”) Exhibit 12 Cruts et al, 1996 Human Molecular Genetics, 5 (Review):1449-1455 Case 1:15-cv-01549-PEC Document 116 Filed 11/05/18 Page 20 of 20