# In the United States Court of Federal Claims

No. 15-1549C (E-Filed: April 27, 2018)

UNIVERSITY OF SOUTH FLORIDA, BOARD OF TRUSTEES,

Plaintiff,

v.

THE UNITED STATES,

Defendant. ) ) ) ) ) ) ) ) ) ) ) ) ) Claim Construction; Markman Hearing; Preamble Construction.

ORDER

In this patent infringement suit, the court has before it the parties’ claim construction arguments. See ECF Nos. 69 , 69-1 (Jt. Claim Construction Statement and Chart); 75 (plaintiff’s initial brie f); 76 (defendant’s initial brief); 83 (plaintiff’s reply brief); 84 (defendant’s reply brief). Also before the court is the transcript of the claim construction hearing held on January 31, 2018. See ECF No. 100 (hearing transcript (Tr.)). This order memorializes the court’s construction of disputed cl aim terms in United States Patent No. 5,898,094 (’094 patent).

I. Background

Plaintiff University of South Florid a, Board of Trustees (USF) holds the rights to the ’094 patent, which is titled “Transgenic Mice Expressing APPK670N,M671L and a Mutant Presenilin Transgenes.” 1 ECF No. 76-1 at 2. The invention in the ’094 patent is presen ted in 14 claims. Id. at 11-12. The claims all discuss a “transgenic mouse” or the methods for screening transgenes and/or for preparing the transgenic mice , id., which are also sometimes described

1 The court will not explai n any technical terms of the ’094 patent in this order. The claimed mice are genetically m odified, i.e., transgen ic, so that they develop a feature (or features) that is char acteristic of Alzheimer’s Disease. The court defers any in-depth discussion of the scientific basis of the ’094 patent for further proceedings in this matter.2 as “doubly transgenic” mice, id. at 8. Su ch mice are of utility in the research of Alzheimer’s Disease (AD) and other neurodegenerative disorders. Id. at 5.

The parties’ positions on claim construction focus on two main controversies, and diverge, as well, as to whether terms in the preambles of the claims require construction. The first controversy is whether the claim terms accelerated and enhanced signify that a characteristic of the transgenic mouse

“occurs at least one month earlier in th e mouse life span,” or merely occurs “earlier in the mouse life span.” ECF No . 69-1. The second controversy is whether the phrase Alzheimer’s Diseas e related pathology signifies the development of a three-component clus ter of AD characteristics, or less specifically signifies that at least one char acteristic of AD, such as “beta-amyloid plaques,” is developed in the transgenic m ouse. Id. Finally, defendant argues that the language in the preambles of certai n claims needs no construction because the preamble language is not limiting. Id.

Of the fourteen claims, the parties have proposed a joint construction of three terms that are found in Claims 1, 3, 5, 7-11, and 13. Id. at 3. The court accepts the parties’ proposed undisputed c onstruction of those te rms, as set forth

in the table attached to this order as A ttachment 1. The parties dispute, however,

the construction of other terms in Claims 1, 3, 5, 7-11, and 13. There are, however, as stated supra, only two princi pal claim construction disputes regarding

the terms in the fourteen claims in the ’094 patent , accompanied by a third question as to whether the preambles of ce rtain claims require construction. The court’s resolution of these disputes is also recorded in the tabl e attached to this

order.

II. Claim Construction

Claim construction “determin[es] th e meaning and scope of the patent

claims asserted to be infri nged.” Markman v. Westview Instruments, Inc., 52 F.3d 967, 976 (Fed. Cir. 1995) (en banc) (citati on omitted), aff’d, 517 U.S. 370 (1996). “[O]nly those terms need be construed th at are in controversy, and only to the extent necessary to resolve the controversy.” Vivid Te chs., Inc. v. Am. Sci. & Eng’g, Inc., 200 F.3d 795, 803 (Fed. Cir. 1999) (cita tion omitted). The court looks first to intrinsic evidence, as “intrinsic evidence is the most significant source of the legally operative meaning of disputed claim language.” Vitronics Corp. v. Conceptronic, Inc., 90 F.3d 1576, 1582 (Fed. Cir. 1996). In trinsic evidence consists of the “patent itself, including the claims, the specification and, if in evidence, the prosecution hist ory.” Id. (citing Markman, 52 F.3d at 979). In the case at bar, there is no need to go beyond the intrinsic evidence of record, which includes the prosecution history, to construe the claims of the ’094 patent. Cf. Tr. at 8 (counsel stating that plaintiff relie s only on intrinsic evidence), 39-40 (counsel stating that defendant believes that intrin sic evidence is suffici ent to sustain the government’s claim construction arguments).3 “[T]he words of a claim are generally given their ordinary and customary meaning.” Phillips v. AWH Corp., 415 F. 3d 1303, 1312-13 (Fed. Cir. 2005) (en banc) (internal quotations an d citations omitted). More precisely, “the ordinary and customary meaning of a claim term is the meaning that the term would have to a person of ordinary skill in th e art in question at the time of the invention, i.e., as of the effective filing date of the pate nt application.” Id. at 1313 (citations omitted). “[T]he pers on of ordinary skill in the art is deemed to read the claim term not only in the context of the par ticular claim in which the disputed term appears, but in the context of the entir e patent, including the specification.” Id.

“Although words in a claim are ge nerally given their ordinary and customary meaning, a patentee may choose to be his own lexi cographer and use

terms in a manner other than their ordi nary meaning, as long as the special

definition of the term is clear ly stated in the patent specification or file history.” Vitronics, 90 F.3d at 1582 (citations om itted). Thus, this court must always “review the specification to determine whether the inventor has used any terms in a manner inconsistent with their ordinary meaning.” Id. While the claim is read in light of the specification, the cour t must not “read[] limitations from the specification into the claim.” Phillips, 415 F.3d at 1323. In addition, the prosecution history of the patent may also be examined to ex clude interpretations disclaimed by the inventor during prosecution. Chimie v. PPG Indus., Inc., 402 F.3d 1371, 1384 (Fed. Cir. 2005) (citing ZMI Corp. v. Cardiac Resuscitator Corp., 844 F.2d 1576, 1580 (Fed. Cir. 1988); V itronics, 90 F.3d at 1582-83 (citations omitted).

Whether a claim’s preamble limits the claim or merely provides an

introduction to the invention is a comm on dispute in claim construction. The United States Court of Appeals for the Fe deral Circuit has discerned a number of general rules governing the co nstruction of terms contai ned in a claim preamble:

In general, a preamble limits the [claimed] invention if it recites essential structure or steps, or if it is necessary to give life, meaning, and vitality to the claim. [A] claim preamble has the import that the claim as a whole suggests fo r it. In other words, when the

claim drafter chooses to use both th e preamble and the body to define the subject matter of the claimed inve ntion, the invention so defined, and not some other, is the one the patent protects. When limitations in the body of the clai m rely upon and derive antecedent basis from the preamble, then the preamble ma y act as a necessary component of

the claimed invention. On the ot her hand, [i]f the body of the claim sets out the complete invention, th en the language of the preamble may be superfluous.

Eaton Corp. v. Rockwell Int’l Corp., 323 F.3d 1332, 13 39 (Fed. Cir. 2003) (internal quotations and citations omitted). The prosecution hist ory of the patent, as well, may help the court to determin e whether the language in the preamble4 limits the claim. E.g., Ap plied Materials, Inc. v. Advanced Semiconductor Materials Am., Inc., 98 F.3d 1563, 1573 (Fed. Cir. 1996) (citations omitted). Although much more could be said on the construction of a claim preamble, these general rules provide a satisfactory frame work for the court’s analysis of the claims in the ’094 patent.

III. Analysis

A. Accelerated or Enhanced M eans “At Least One Month Earlier”

The parties’ first dispute in claim c onstruction is quite straightforward. Plaintiff argues that the adjectives acce lerated and enhanced both signify that a desired characteristic (or characteristics) appears “at least one month earlier” in the life span of the transgen ic mouse. ECF No. 75 at 42 -44. Defendant contends

that the terms accelerated and enhan ced do not signify that the desired characteristic appears at least one month ea rlier in the life span of the transgenic mouse, but simply signify that the desired characteristic occurs “e arlier” in the life span of the tr ansgenic mouse. 2 ECF No. 76 at 15-20. Pl aintiff offers the correct

construction of these two terms.

Plaintiff asserts that the ’094 patent contains a de finition of accelerated and

enhanced that falls within the “patentee acting as his own lexicographer” line of cases. ECF No. 75 at 30-32, 42. The court must agree. One statement in the ’094 patent’s specification, in particular, strongl y supports this construction of the terms

accelerated and enhanced:

2 The government’s position as to th e meaning of the term enhanced is variable, where sometimes th e term means “earlier,” wh ereas at other times, the term means “more.” Compare ECF No. 76 at 33-34, with ECF No. 84 at 11-12,

with Tr. at 40-41. This lack of consis tency in the government’s interpretation of the term enhanced does not strengthen its claim construction arguments. The court notes, too, that the government’s description of the position of its former co-defendant regarding the constructi on of the term enhanced also lacks consistency. Compare ECF No. 76 at 34 (s tating that the former co-defendant did not agree with the government’s construc tion of enhanced), with ECF No. 84 at 11 (stating that the former co-d efendant agreed with the government’s construction of enhanced).5 Where earlier or accelerated, it is me ant that the observed phenotype

is seen at least one month earlier in the lifespan than the phenotype in the parental strain or similarly for later appearance.[ 3 ]

ECF No. 76-1 at 7 (’094 patent 5:18-21). Thus, the adjective accelerated has been given the definition in the ’094 patent of “at least one month earlier in the life span” of the transgenic mouse. Id.

Although the adjective enha nced is not directly defined in this same section of the specification of the ’094 patent, the court notes that, in the claims where the term enhanced occurs, the parallel use of the terms accelerated and enhanced is striking. Claim 1 announces that the transgenic mouse will have “enhanced Alzheimer’s Disease related amyloid accumu lation in its brain” such that the “mouse develops accelerat ed deposition of A β in its brain.” Id. at 11. Similarly,

Claim 13 announces that the method for producing this transgenic mouse that has

“enhanced Alzheimer’s Disease related am yloid pathology” w ill ensure that the mouse “develops accelerated deposition of AD[ 4 ] in its brain.” Id. at 12. As evidenced by the parallelism within Claims 1 and 13, enhanced and accelerated are used in the ’094 pate nt claims as synonyms.

Because accelerated means “at least one month earlier in the life span” of the transgenic mouse, and because ac celerated and enhanced are used as synonyms, the court finds th at both accelerated and e nhanced mean “at least one month earlier in the life span” of the tran sgenic mouse. Th is construction is consistent with the patent specificati on which places great emphasis on producing

mouse models for AD research where the tr ansgenic mice exhibit desired traits earlier in their life spans. See ECF No. 76-1 at 6 (’094 patent 3:57-67; 4:1-4), 8 (’094 patent 8:15-26). For these reasons , the court construes accelerated and enhanced to signify “at least one month ea rlier in the life span ” of the transgenic

mouse.

Defendant proffers a number of argum ents against this construction, but

none is sufficient to overco me the most reasonable re ading of the text of the claims and specification of the ’094 patent . First, the government argues that the definition of accelerated is of limited ap plicability because it only appears in the

3 For the purposes of this analysis, a phenotype may be considered to be a characteristic or set of characteristics presen t in a transgenic mouse. See Tr. at 8, 10-11, 30.

4 The term “AD” is a likely typogra phic error in the’0 94 patent replacing

“A β .” Cf. ECF No. 69-1 at 6 (where neither party proposes that Claim 13 specifies an earlier deposition of Alzhei mer’s Disease, but instead both parties suggest that Claim 13 specifies an earlier de position of amyloid pl aque features (or beta-amyloid plaques).6 Preferred Embodiment section of the ’094 patent. ECF No. 76 at 18; ECF No. 84 at 7-8. Although the court agrees with defendant that it may be error to limit a claim in light of language found only in a preferred em bodiment of the invention, e.g., Liebel-Flarsheim Co. v. Medrad, In c., 358 F.3d 898, 904- 08 (Fed. Cir. 2004), the language in a preferred embodiment of a patent may limit a claim if the limiting language is consistent with the inventor’s general description of the invention, e.g., Biogen, Inc. v. Berlex Labs., Inc., 318 F.3d 1132, 1139-40 (Fed. Cir. 2003) (citations omitted). Here, because the definition of accelerated, and, by extension, of enhanced, is of general a pplicability to the inve ntion in the ’094 patent, it is not error to utilize that defin ition which is found in the sole preferred embodiment described in the ’094 patent.

The government’s second argument makes a distinction between mice of the “parental strain,” ECF No . 76-1 at 7, which are cont rasted with the invented strain of transgenic mice in the Preferred Embodiment, and other groups of mice

that are contrasted with the transgenic mice of the ’094 patent in the language of Claims 1, 3, 7-8, 10-11, and 13. ECF No. 76 at 19-20; ECF No. 84 at 8. At oral argument, counsel for plaintiff took the position that the distinctions between non-transgenic mice, singly transgenic mice, and parental transgenic mice as comparators for the claimed doubly transg enic mice are dis tinctions without a difference. Tr. at 46-47, 55. Counsel for defendant argued that these distinctions between parental and non-parental mice must be accorded some significance. Id. at 53-54. The court agrees with plainti ff. When the descriptors accelerated and enhanced are construed, the comparative be nefit of “at least one month earlier in the life span” of the transgenic mous e is of equal benefit no matter which comparison group is selected. The dis tinctions between non-transgenic mice, singly transgenic mice, and parental transg enic mice are of no consequence for the

construction of the claim terms accelerated and enhanced.

Third, the government argues, more generally, that the cited definitional sentence containing the phrase “at least one month earlier in the life span” of the transgenic mouse is vague, unclear, a nd not rigorous enough to serve as a

definition for the terms accelerated and en hanced. ECF No. 76 at 17-19; ECF No. 84 at 6-7. The court disagrees. This is not a case where a party urges the court to pluck one particular definition from a thicket of competing and confused definitions in the specification of a patent. Here, the term accelerated is precisely defined in the ’094 patent only by the sentence cited by plaintiff, ECF No. 76-1 at 7 (’094 patent 5:18-21), and the terms accelerated and enhanced take their definition from this sentence. The language relied upon by plainti ff is clear and is
not vague.

Fourth, the government suggests that its claim construction, one which equates accelerated with an unspecified “ earlier” amount of time, is consistent with various expressions in the specif ication and also raises no risk of indefiniteness. ECF No. 76 at 16; ECF No. 84 at 9-10. Plaintiff strongly disagrees. ECF No. 75 at 43-44. Plain tiff urges the court to adopt its claim construction to preserve the validity of th e ’094 patent, and to avoid construing7 accelerated and enhanced in a manner that renders the claims of the ’094 patent indefinite. Id. at 44 (citing Whittaker Co rp. v. UNR Indus., Inc., 911 F.2d 709, 712 (Fed. Cir. 1990)). The court does not believe that the rule set forth in Whittaker applies here. See 911 F.2d at 712 (stating that “claims are generally

construed so as to sustain their valid ity, if possible”) (citation omitted).

The rule that patent claims are ge nerally construed to preserve their validity, if possible, is “a doctrine of limite d utility.” Phillips, 415 F.3d at 1328. It does not apply when the claim is una mbiguous, nor does it apply when a claim

“can be construed without the need to co nsider whether one possible construction

would render the claim invalid while the ot her would not.” Id. Here, the meaning

of the claim terms accelerated a nd enhanced is not ambiguous.

However, the court recognizes that “broad and amorphous” claim terms, such as accelerated and enhanced, be nefit from a close reading of the specification. See, e.g., Bell Atl. Netw ork Servs., Inc. v. Covad Commc’ns Grp., Inc., 262 F.3d 1258, 1269-70 (F ed. Cir. 2001) (Bell Atlantic ) (noting, in that case, that “the ordinary meaning of the non-te chnical term ‘mode’ is sufficiently broad and amorphous that the scope of the clai m language can be reconciled only with recourse to the written description” (c iting Comark Commc’ns, Inc. v. Harris Corp., 156 F.3d 1182, 1187 (Fed. Cir. 1998))). Here, fo llowing the rule in Bell Atlantic, the court relies upon the speci fication to supply the definition of accelerated and enhanced; that definition re nders the patent cl aims unambiguous. Thus, the court need not constr ue the ’094 patent claims to preserve their validity. Phillips, 415 F.3d at 1328.

Alternatively, if the ’094 patent claims could be considered to be ambiguous, the court would agree with plaintiff that the claims should be construed to preserve their validity . Under the government’s proposed construction of accelerated and enhanced, ECF No. 84 at 9-12, the invention is likely indefinite because there are no objec tive boundaries to the terms of degree earlier, or more. See, e.g., Berkheimer v. HP Inc., 881 F.3d 1360, 1364 (Fed. Cir. 2018) (“Our case law is clear that the obj ective boundaries requirement applies to terms of degree.”); Liberty Ammunition, Inc. v. United States, 835 F.3d 1388, 1395-96 (Fed. Cir. 2016) (“We especially take caution when presented with terms of degree following the Supr eme Court’s decision in Na utilus, Inc. v. Biosig Instruments, Inc., [134 S. Ct. 2120] (2014)” ), cert. denied, 137 S. Ct. 1825 (2017). Thus, if the claims of the ’094 patent c ould be deemed to be ambiguous in their

use of the terms accelerat ed and enhanced, the cour t would adopt plaintiff’s

construction of these terms to preserve the claims’ validity.

Finally, the government argues that pl aintiff’s proposed construction of the term enhanced is flawed, because no suffi cient definition of this term in the specification of the ’094 pa tent displaces the ordinary meaning of the term

enhanced. ECF No. 76 at 34; ECF No. 84 at 11-12. In the same vein, the government also relies on a discussion of the term enhanced during the prosecution history of th e ’094 patent. ECF No. 84 at 12. Beyond these two8 arguments that rely on intrin sic evidence, the government relies, in addition, on a dictionary definition of the verb “enhance” to suggest that the definitions “more,” “raise[d]” or increase[d]” capture the mean ing of the term enhanced in the claims of the ’094 patent. Id. at 12; see also ECF No. 76 at 34; Tr. at 41.

Plaintiff argues, and the court has foun d, that the specification provides a

definition for accelerated and enhanced so th at in the claims of the ’094 patent,

enhanced means “at least one month earlier in the life span” of the transgenic

mouse. ECF No. 75 at 30-32. According to plaintiff,

[t]here is nothing in the Specifica tion, nothing in the Prosecution History or any other aspect of th e intrinsic evidence that suggests [that] the term “accele rated” or “enhanced” ca n mean anything but at

least one month earlier in th e lifespan of the mouse.

Id. at 31. The court agrees with plainti ff that enhanced, as used in Claims 1 and 13, must be construed to indicate that the de sired trait (or traits) occurs at least one month earlier in the life span of the transgenic mouse.

In the court’s view, the ex trinsic evidence of the di ctionary definition of the verb “enhance” does not outweigh the sp ecification language relied upon by plaintiff, and the parallel use of accelerated and enhanced in Claims 1 and 13. See supra. Further, the unenlightening disc ussion of the term enhanced which took place during the prosecution hi story of the ’094 patent, one which referenced, in the government’s words, “generic terminol ogy in the prior art,” ECF No. 84 at 12, also does not replace the clear definition of the term enhan ced provided by the specification and by the parallel use of the terms accelerated and enhanced in Claims 1 and 13. Ambiguous statements in the prosecution history should be accorded less weight than the specification lang uage of the patent itself. See, e.g., Phillips, 415 F.3d at 1317 (“[B]ecause the prosecution history represents an ongoing negotiation between the [United States Patent and Trademark Office (PTO)] and the applicant, ra ther than the final product of that negotiation, it often lacks the clarity of the specification and th us is less useful for claim construction purposes.”) (citations omitted). Having cons idered all of defendant’s arguments as

to the construction of the term enhanced in Claims 1 and 13, including those that rely on extrinsic evidence, not just intrinsic evidence, the court concludes that plaintiff’s construction of the term enhanced is correct. 5

5 Defendant also contends that beca use the word enhanced appears along

with the word accelerated in some sentences within the specification, this phenomenon supports the government’s c onstruction of the term enhanced. ECF No. 84 at 12 (citing ’094 patent 4:3-4; 4:9). As plainti ff’s counsel noted at oral argument, however, the paramount concern of timing in the ’094 patent supports plaintiff’s construction of the term enha nced in Claims 1 and 13, i.e., that9 B. Alzheimer’s Disease Related Pathology

The second claim constructi on dispute in this case is also straightforward. Plaintiff contends that any mention in the claims of the ’094 patent of Alzheimer’s Disease related pathology, or some variant of that phrase, necessarily refers to a constellation of three markers for AD pa thology, wherein the transgenic mice manifest: (1) fibrillary deposits of Aß; (2) reactive gliosis; and, (3) a loss of spontaneous alternation behavior. ECF No. 75 at 53. Defendant, on the other hand, urges construction of the term Al zheimer’s Disease related pathology --

should the court decide that this language limits any claim in the ’094 patent -- to mean “having a characteristic of Al zheimer’s disease (e.g., beta-amyloid plaques).” ECF No. 76 at 22, 32-33. In the court’s view, defendant’s construction

of this term hits closer to the mark.

Plaintiff’s proposed construction de pends on two foun dational premises, both of which are fundamentally flawed. 6 The first premise is that the applicants acted as their own lexicogra pher, before the PTO, to su bstitute a special definition for Alzheimer’s Disease related pathol ogy that displaces the ordinary and customary meaning of this term. ECF No . 75 at 10, 45-46; ECF No. 83 at 34-35, 41; Tr. at 16-19. The second premise is th at the specification of the ’094 patent clearly sets forth a definition for Alzh eimer’s Disease related pathology that requires that all three traits -- fibrillary deposits of Aß; reactive gliosis, and the loss of spontaneous alternation behavior -- occur in the claimed doubly transgenic mouse. ECF No. 75 at 32-34, 45; ECF No . 83 at 29-32, 40; T r. at 13-16, 20, 44- 45, 55. Neither of these pr emises is supported by the intrinsic eviden ce before the

court.

1. Prosecution History Evidence

enhanced means “at least one month earlier in the life span” of the transgenic

mouse. Tr. at 51.

6 Plaintiff’s proposed claim construction also suffers from an inconsistency. Plaintiff argues, on one hand , that when a specific AD re lated pathology is cited in a claim, this specific reference shows th at the claim does not require that the claimed mouse display all three desirable tra its. See ECF No. 75 at 46 n.6. On the other hand, in its proposed claim constructions, plainti ff specifically proposes a

construction which states that the mice de scribed in Claims 8 and 9 must display all three desirable traits, notwithstandi ng the claim language in Claims 8 and 9 citing one specific AD related pathology. ECF No. 69-1 at 8; ECF No. 75 at

58-59. These statements advance fundam entally inconsistent and contradictory claim construction positions.10 Plaintiff acknowledges that its reli ance on prosecution history is somewhat distinctive, in that the lexicographer who purportedly replaced the plain meaning of Alzheimer’s Disease related patholog y with a specialized definition was the patent examiner, not the applicant. Tr. at 19. “The crafter of the claims, which is often the applicant, but in this case was the Examiner, as a result of discussion and exchange between the two in prosecution, formulated a specific definition that applicants attempted to embrace and the Ex aminer wrote for them.” Id. While the court does not categorically reject plaintiff’s theory that a patent examiner may, in certain circumstances, assist the applicant in lexic ography, here there is no evidence that the applicants rewrote th e patent to incorporate any specific

definition of Alzheimer’s Disease rela ted patholo gy provided by the patent examiner, or that they manifested any type of assent to the definition that might have been proposed by the patent examiner. Indeed, as defendant argues, the prosecution history of the ’0 94 patent shows that the applicants did not expressly adopt the definition allegedly proposed by the patent examiner, and that the applicants may have, instead, rejected the examiner’s proposed formulation. ECF

No. 84 at 21-24.

The court has carefully ex amined the exhibits attach ed to the parties’ claim construction briefs relevant to the dialog ue between the applic ants and the patent examiner. See ECF Nos. 75-2; 75-3; 75-4; 76-2. While it is true that the patent examiner noted, on March 12, 1998, th at three characteristics of AD were implicated by traits obtained in the cl aimed doubly transgenic mice, see ECF No. 75-2 at 3-5, 7, these comments by the examiner did not elicit any affirmative amendments to the patent reproducing the language employed by the examiner, nor did the applicants acknowledge that the examiner had provi ded the specialized definition that would govern the interpre tation of the term Alzheimer’s Disease related pathology in the ’094 patent. Indeed, on June 15, 1998, the applicants, instead, referenced “increased levels of amyloidogenic Aß” as the “enhanced AD phenotype” obtained in the claimed mice. ECF No. 75-3 at 19. In other statements communicated to the patent exam iner on June 15, 1 998, the applicants noted that the “[t]he amyloid patholog y is generally increased levels of amyloidogenic Aß,” and that the clai med mice show “accelerated amyloid deposition.” Id. at 14-15. On this record , a person of ordinary skill in the art was not aware from the prosecution history of th e ’094 patent that the applicants had adopted a specialized definition of the te rm Alzheimer’s Diseas e related pathology that originated with the patent examiner.

To the extent that plaintiff asserts th at its prosecution history analysis is on all fours with any of the caselaw cited in pl aintiff’s briefs or at oral argument, see ECF No. 75 at 50; Tr. at 8, the court disagrees. In Biogen Idec, Inc. v. GlaxoSmithKline LLC, 713 F.3d 1090, 1093-94, 96-97 & n.6 (Fed. Cir. 2013), for example, the district court adopted a cl aim construction based on the applicant’s explicit acknowledgement of a limitation pr oposed by the patent examiner, and the Federal Circuit affirmed on this ground. Similarly, in Aptalis Pharmatech, Inc. v. Apotex Inc., No. 2017-1344, 2018 WL 286123, at *4-5 (Fed . Cir. Jan. 4, 2018), an unpublished decision cited by plaintiff, the Federal Circuit found support for the11 appellants’ claim constructi on position in the language of a declaration submitted by the applicants during the prosecuti on of the patent, which summarized a dialogue between the patent examiner and an expert in the field of the invention. In these cases cited by plaintiff, the defining language was submitted or acknowledged by the applicant in the course of prosecution. In this case, in contrast, plaintiff attempts to leverage a statement of the patent examiner, one that is unaccompanied by any acknowledgmen t or adoption on the part of the applicants, to support plaintiff’s proposed claim construction.

Neither the intrinsic evidence of th e prosecution history, nor the caselaw relied upon by plaintiff, supp orts plaintiff’s proposed claim construction. The court concludes that the pr osecution history of the ’094 patent does not support plaintiff’s proposed cons truction of the term Alzh eimer’s Disease related pathology. The court now turns to plain tiff’s arguments based on the specification of the ’094 patent.

2. Specification Language

At oral argument, the court asked plaintiff’s counsel to identify “more specific cites” to the specification that s upport plaintiff’s propo sed construction of

the term Alzheimer’s Disease related pathology. Tr. at 14. To answer the court’s question, counsel pointed to Columns 5-8 of the ’094 patent, as well as to Columns 9-11. Id. at 14-16. According to the court’s calculation, the definition for Alzheimer’s Disease related pathology, as related by plaintiff, must be distilled

from more than four hund red lines of text of the patent specification, encompassing the entirety of the “Det ailed Description of the Preferred Embodiment,” as well as almost the entir ety of the “Examples” section. See ECF No. 76-1 at 7-10. There is no summarizing sentence or paragraph in this wide swath of text that provides the three-comp onent specialized definition that plaintiff urges the court to adopt. Nor, as defend ant points out, does the term “reactive gliosis,” which is part of plaintiff’s de finition of the contested term Alzheimer’s Disease related pathology, appear anywhere in the ’094 patent. 7 See ECF No. 84 at 15 n.12. Thus, plainti ff’s effort to conv ince the court that its proposed

definition for “Alzheimer’s Disease related pathology” is “clearly stated” in the specification is completely at odds with the text of the specification. Vitronics, 90

F.3d at 1582.

Plaintiff notes, nonetheless, that th e “patent Specification considers the fibrillary amyloid deposits in the brain, reactive gliosis and loss of spontaneous alternation behavior.” ECF No. 75 at 45 (c iting ’094 patent 10:22 to 11:37). This is a plausible reading of the specificati on, but the extended discussion in the specification of these three desired traits in the claimed mice is unmoored from

7 Plaintiff’s counsel was therefore imprec ise when he stated that “the loss of nerve cells, astrocytes, [was] generally referred to as reactive gliosis in the patent.”

Tr. at 13.12 any definitional statement that all three of these characteristics must be present for the phrase Alzheimer’s Disease related pathol ogy to have meaning. Plaintiff thus invites the court to improperly import a limitation from the spec ification into the claims, when the court must, instead, read th e claims in light of the specification. Phillips, 415 F.3d at 1323.

In its reply brief, plaintiff urges the court to consider the penultimate paragraph of the Preferred Embodiment sect ion of the ’094 patent, which contains a summary, of a sort, of the advantages of the claimed mice. ECF No. 83 at 29-30.

The cited text is as follows:

These results clearly demonstrate that presenilin mutations accelerate development of the AD phenotype in K670N,M671L mice in a synergistic manner and provides a modulated phenotype. The data indicate that mutant presenilin affe cts the processing of mutant APP expressed from the K670N,MG71L transgene to enhance Aß production, fibrillar plaque formation and affect behavior early in the life-spans of mice. The rapid development of the AD phenotype in these mice will be advantageous in addressing mechanistic issues of amyloid toxicity, and testing the efficacy of agents proposed to

interact with select as pects of the AD phenotype.

ECF No. 76-1 at 8 (’094 patent 8:15-26). This section of the patent does not aid plaintiff. Any three-component definition of the term Alzheimer’s Disease related pathology that could be derived from this paragraph is captured in the phrase “to enhance Aß production, fibrilla r plaque formation and affe ct behavior early in the life-spans of mice.” Id. The three components of any such definition do not include reactive gliosis or any mention of astrocytes, and any such definition doubles the emphasis on Aß production and fibrillar Aß deposits/plaques. Again, the text of the specification contains no support for plaintiff’s proposed three-component definition of the term Alzheimer’s Disease related pathology.

The court has considered all of the parties’ arguments based on the specification and the language and structur e of the claims which contain the term Alzheimer’s Disease related pathology. None of these arguments convince the court that the specification contains the three-component specia lized definition of that term proposed by plain tiff. The court therefore turn s to defendant’s proposed

construction of this term.

Defendant argues that the correct c onstruction of the term Alzheimer’s Disease related pathology is “having a char acteristic of Alzheimer’s disease (e.g., beta-amyloid plaques).” ECF No. 69-1 at 4-5; ECF No. 76 at 22. Plaintiff, somewhat incongruously, finds the use of the word “plaques” in defendant’s construction to be inappropriate, on th e grounds that the word “plaque” is “nowhere substantively employed” in the ’094 patent. ECF No. 75 at 47. As defendant notes, plaintiff’s resistance to the use of the word “plaques” is undermined by plaintiff’s use of the ph rase “plaque features” in one of its13 proposed constructions of the term Alzhei mer’s Disease related pathology. See ECF No. 69-1 at 4-8; ECF No. 84 at 15 n.12.

The court notes, too, that the word “plaque” is mentioned several times in the ’094 patent -- in the title s of prior art publications, in the Background of the Invention section, in the Preferred Embodim ent section, in the Examples section, and in a table of test results comparing th e claimed mice to singly transgenic mice. ECF No. 76-1 at 3, 5, 8-11. The pate ntee appears to have made substantive employment of the word “plaque.” 8 Defendant suggests, in any case, that the court might substitute the word “depos ition” for “plaques,” in defendant’s proposed construction, to address plaintiff’s concern. See ECF No. 84 at 15 n.12. Indeed, in the court’s view, if the occurrence of the words “deposits” or “deposition” is tracked thro ughout the ’094 patent, th is formulation is more

common than the substantive use of the word “plaque.”

Having considered the almost innumera ble variations in the description of amyloid deposits in the mouse brain that ar e contained in the ’094 patent, the court believes that the “formation of deposits co ntaining Aß in the br ain” captures this concept. See, e.g., ECF No . 76-1 at 8 (’094 patent 7: 57-58), 9 (’094 patent 9:63), 10 (’094 patent 11:9). Thus the court slightly alters de fendant’s proposed construction, and construes the term Alzh eimer’s Disease related pathology in the following manner: “having a characteristic of Alzheimer’s Disease, such as the formation of deposits containing Aß in the brain.” This formulation is in accordance with the language of the specification, and also is in accordance with the phrasing of the invention in a great number of the claims, where the claimed mouse or mice “develop[s] . . . deposition of Aß in its [or their] brain[s].” ECF No. 76-1 at 11-12 (Claims 1, 3, 5, 7, 10, 13). 9

Plaintiff invokes the claim differentiati on doctrine in an effort to convince the court that defendant’s proposed clai m construction of the term Alzheimer’s Disease related pathology is infirm. EC F No. 75 at 11-12, 47-48; ECF No. 83 at 36-37; Tr. at 20. Plaintiff argues that if the term Alzheimer’s Disease related pathology means “having a characteristic of Alzheimer’s Disease, such as the formation of deposits containing Aß in th e brain,” this term is too similar to the

term “accelerated or enhanced deposition of Aß in the br ain,” another term of art found in many of the claims of the ’094 patent. The court does not agree.

The preambles of the claims contain the term Alzheimer’s Disease related pathology, which refers to any one of the characteristic s of Alzheimer’s Disease,

8 At least as compared to plaintiff’s proposed use of the term “reactive gliosis,” which is nowhere employed in the ’094 patent, th e word “plaque” is substantively employed in the patent.

9 Correcting for a likely typographic error in Claim 13, substituting Aß for AD. See supra note 4.14 such as the formation of deposits containi ng Aß in the brain, whereas the body of the claim specifically notes that accelerated or enhanced deposition of Aß occurs in the brains of the claimed mice. Although these terms are similar, they are easily distinguished. The court notes, too, th at the claim differentiation doctrine is merely a rule of thumb that does not trump clear indicators of meaning found in the specification. E.g., Edwards Lifesc iences LLC v. Cook Inc., 582 F.3d 1322, 1332 (Fed. Cir. 2009) (citing Netcraft Corp. v. eBay, In c., 549 F.3d 1394, 1400 n.1 (Fed. Cir. 2008)). Even if defendant’s construction of the term Alzheimer’s Disease related pathology offended the do ctrine of claim differentiation, which it does not, that doctrine would not outweigh th e language of the specification -- and of the claims themselves -- which provide s the proper construction of this term.

Further, the prosecution history of the ’094 patent clearly identifies five

characteristics of Alzheimer’s Disease that would be useful in transgenic mice: fibrillar Aß deposits, reactive gliosis, increased maze activity, neurofibrillary tangles, and massive neuronal loss. ECF No. 75-2 at 5. The court’s construction

of the term Alzheimer’s Dis ease related pathology takes this fact into account by stating that “having a characteristic of Al zheimer’s Disease, su ch as the formation of deposits containing Aß in the brain,” is a feature of the invention in the ’094 patent. The court’s construc tion of the disputed term re flects both the prosecution history and the specification of the ’094 pa tent, and allays any concern that this term is not sufficiently differentiated fro m other terms in the claims of the ’094 patent which focus solely on Aß accumulation or deposits. 10

Thus, the court adopts a slightly m odified form of defendant’s proposed

construction. The term Alzheimer’s Diseas e related pathology in the claims of the ’094 patent means “having a characteristic of Alzheime r’s Disease, such as the formation of deposits containing Aß in the brain.” The cour t now turns to the parties’ final dispute, where plaintiff a nd defendant disagree as to whether the claims’ preambles limit the claims of the ’094 patent.

C. Preamble Language

There are two facets to this dispute. First, plaintiff appears to suggest that the court should not decide, during the Markman phase of this litigation, whether the language of the claim preambles limits the claims. See Tr. at 19 (“This is not

10 The court must disagree with defenda nt that the word “pathology” excludes cognitive deficits associated w ith Alzheimer’s Disease. C f. Tr. at 39. The text of the specification relied upon by defendant is ambiguous, see ECF No. 76-1 at 6 (’094 patent 3:3-8), and runs counter to the discussion of AD pathology in the prosecution history, see EC F No. 75-2 at 5. Because the intrinsic evidence is

sufficient to show that cognitive impairments are en compassed in the term pathology in the ’094 patent, the court ne ed not turn to extrinsic evidence to construe the word pathology.15 the time, we submit, that you determine wh ether the preamble is limiting or not, although the parties have discussed [this i ssue] in their briefs.” ), 48 (“Our view of the case law says this is not the time [t o determine whether a preamble limits a claim].”). Second, if the question is properl y before the court at this time, plaintiff suggests that the preamble language is lim iting, whereas defendant argues that the preamble language of the ’094 patent clai ms is not limiting. The court addresses each of these questions in turn.

1. Determining Whether the Pr eamble Is Limiting Is Part of

Claim Construction

Plaintiff’s hypothesis, that clai m construction does not include a determination of whether a preamble limits a claim, was not clearly presented until oral argument, although a vague precurso r of this hypothesis was presented in plaintiff’s reply brief. 11 As such, plaintiff’s argument is not properly before the court. See, e.g., Novosteel SA v. Un ited States, 284 F.3d 1261, 1274 (Fed. Cir. 2002) (finding that a party waived an argum ent that was first presented to the trial judge in a reply brief); Cubic Def. Sys., In c. v. United States, 45 Fed. Cl. 450, 467 (1999) (finding that a party waived argume nts presented for the first time at oral argument). Nor was plaintiff’s contentio n at oral argument supported by any

citation to caselaw. 12 Even so, plaintiff’s hypothesis is quickly rebutted by reference to any number of decisions of the Federal Circuit, where that court addressed the status of a claim preamble, as limiting or not limiting, in the context of claim construction. See, e.g., Pacing Techs., LLC v. Garmin Int’l, Inc., 778 F.3d 1021, 1023 (Fed. Cir. 2 015) (noting that the claim construction dispute in that case “turn[ed] on whether the preamble to claim 25 is limiting and on the construction of a ‘repetitive motion pacing system’ as recited in the preamble”); Bicon, Inc. v. Straumann Co., 441 F.3d 945, 952 (Fed. Cir. 2 006) (considering an appellant’s arguments concerning “the role of preamble language in claim construction” and finding that certain preamble language limited the claim); Schumer v. Lab. Comput. Sys., Inc., 308 F.3d 1304, 1310 (Fed. Cir. 2002) (finding error in a district court’s clai m construction becaus e that construction mistakenly found that the preambles limited th e claims); Bell Commc’ns Research, Inc. v. Vitalink Commc’ns Co rp., 55 F.3d 615, 621 (Fed. Cir. 1995) (Bell Communications) (“Preamble construc tion thus presents no deeper mystery

than the broader task of claim construction, of wh ich it is but a part.”).

11 Plaintiff stated in its reply brief that “claim terms are construed on the basis of the patent’s file history, not whether th ey are ‘limiting’ or not.” ECF No. 83 at

26.

12 Indeed, plaintiff’s initial claim constr uction brief suggested that this is the time for the court to decide whether langua ge in the preambles is limiting on the claims of the ’094 patent, because that ve ry topic was addressed at some length.

ECF No. 75 at 12-15.16 The correct approach to preamble s and the claim limitation issue is supplied, in part, in Schumer. Language in a claim preamble is of no significance to claim construction where the preamble does not limit the claim. Schumer, 308 F.3d at 1310 (citing Bristol-Myers Squibb Co. v. Ben Venue Labs., Inc., 246 F.3d 1368, 1373-74 (Fed. Cir. 2001)). In such a situation, the preamble language is superfluous. Id. (citing Manning v. Para dis, 296 F.3d 1098, 1103 (Fed. Cir. 2002)). Where, however, a preamble may limit a claim, the court may need to construe terms contained in the preamble , and determine whether the preamble is limiting, to construe the claims of the pate nt. See, e.g., Seachange Int’l, Inc. v. C-COR, Inc., 413 F.3d 1361, 1375-77 (Fed. Cir. 2005) (construing terms in a preamble and finding that the preamble was limiting); Catalina Mktg. Int’l, Inc. v. Coolsavings.com, Inc., 289 F.3d 801, 811 (Fed. Cir. 20 02) (construing a term in both a preamble and the body of the clai m and deciding that the preamble was limiting). Thus, in this case, the court has first construed the di sputed terms in the claim preambles, and now must determin e whether the preamble language limits the claims in the ’094 patent to complete its claim construction task. 13

2. The Preamble Language Is Limiting in This Case

Many of the preamble construction gu idelines cited by the parties are of potential relevance to the question of wh ether the claim prea mbles of the ’094 patent are limiting. Unfortunately, th ese guidelines can prove to be ambiguous and produce widely varying results at th e trial level and upon appeal. For example, simply because a preamble appear s to contain an “antecedent basis” for a term mentioned in the body of a claim is no guarantee that the preamble is limiting. See Eaton, 323 F.3d at 1339 (“ When limitations in the body of the claim rely upon and derive ant ecedent basis from the preamble , then the preamble may act as a necessary component of the cl aimed invention.”) (emphasis added) (citations omitted). The preamble language must still supply some additional, vital information that is missing from the body of the claim for that particular guideline to apply. See, e.g., TomTom , Inc. v. Adolph, 790 F.3d 1315, 1322-24 (Fed. Cir. 2015) (ruling that certain pr eamble terms were not limiting because these terms were merely duplicative of the terms in the body of the claim, even though the preamble did provide an antece dent basis for another term in the body of the claim) (citations omitted); Am. Med. Sys., Inc. v. Bio litec, Inc., 618 F.3d 1354, 1359 (Fed. Cir. 2010) (“We have he ld that the preamble has no separate

13 In this particular case, it would have been difficult to determine whether the preamble language limits the claims in the ’094 patent without first construing the disputed terms within the preambles. Another approach would be to first determine whether the preamble contains a claim limitation. See, e.g., Symantec Corp. v. Comput. Assocs. Int’l, Inc ., 522 F.3d 1279, 1288 (Fed. Cir. 2008) (“Because the disputed term appears in the preamble to claim 1, we must first determine whether it is in fact a separate [claim] limitation.”). In the instant case, the end result would necessarily be the same.17 limiting effect if, for example, ‘the pream ble merely gives a descriptive name to the set of limitations in the body of th e claim that completely set forth the invention.’” (quoting IMS Tech., Inc. v. Haas Automation, Inc., 206 F.3d 1422, 1434-35 (Fed. Cir. 2000))).

The court relies, therefore, on one pa rticular guideline that, under the facts of this case, is dispositive for the constr uction of the claims in the ’094 patent:

[C]lear reliance on the preamble dur ing prosecution to distinguish the claimed invention from the prior art transforms the preamble into a

claim limitation because such reli ance indicates use of the preamble to define, in part, the claimed invention.

Catalina, 289 F.3d at 808-09 (citation omitted). When such evidence is found in the prosecution history of the patent, th e drafter has chosen “to use both the preamble and the body to define the subjec t matter of the claimed invention, [and] the invention so defined, and not some othe r, is the one the patent protects.” Bell Communications, 55 F.3d at 620 (citations om itted). Because the drafting of each of the claims of the ’094 pa tent shows an intent to us e the preamble to distinguish the claimed invention from the prior art, the preamble term s limit the claims.

Both parties in this litigation have ac knowledged that the patent examiner’s

concerns about the initial version of the ’094 patent led to ex tensive revisions of the language of the claims in the ’094 patent. ECF No . 75 at 38; ECF No. 84 at 20-21. The record shows, and defendant acknowledges, that substantive changes were made to the claim preambles to a ddress the examiner’s concerns. ECF No. 76-2 at 44-50; ECF No. 76-6 at 2-7; ECF No. 84 at 20-21. According to plaintiff’s counsel, a key term in the claim prea mbles was “coined” by the examiner and “embraced” by the applicants. Tr. at 19. Having studied the prosecution history and the parties’ interpretation of that hi story, the court concludes that the claim preambles were designed to distinguish the claimed invention from the prior art and to ensure that other concerns, such as enablement, were addressed. This history satisfies, in the court’s view, th e requirement for a “cl ear reliance on the preamble during prosecution.” Catalina, 289 F.3d at 808-09 (citation omitted).

In this context, the variation in th e preambles among the claims in the ’094 patent has little significance for the inquiry into whether these preambles contain claim limitations. The prosecution history of the ’094 patent shows that both the preamble and the body of each claim functio ned as coordinated expressions of the

invention. Bell Communica tions, 55 F.3d at 620 (cita tions omitted). The court has considered all of defendant’s arguments to the contrary but finds that these18 arguments ignore the impact of the patent examiner’s extensive restructuring and rewriting of the claims in the ’094 patent. 14

Finally, even if the court were to ig nore the prosecution history of this patent, which it should not, defendant’s atta ck on the preambles is based largely on defendant’s assertion that the preamb les are superfluous. ECF 76 at 21-22; ECF No. 84 at 13. They are not. The cl aim preambles that include the disputed term Alzheimer’s Disease related patholo gy, for example, namely the preambles of Claims 3, 5, and 7, cann ot be considered to be supe rfluous. This disputed term, as construed here by the court, introd uces a broader definition of AD related characteristics than otherwise is present in each of these claims. The preamble states that an AD related characteristic, which might or might not be the specific example of the “formation of deposits containing Aß in the brain,” is accelerated

in the claimed mouse. That is not a s uperfluous statement of a claim limitation.

For the above reasons, the court finds that the preambles of the ’094 patent are limiting and that the disputed terms w ithin those preambles must be construed as part of the claim construction task be fore the court. Catalina, 289 F.3d at

808-09.

IV. Conclusion

The court sets forth its construction of disputed claim terms in the table that

is attached to this orde r (Attachment 1). The court construes accelerated and enhanced to signify “at least one month ea rlier in the life span ” of the transgenic

mouse. The term Alzheimer’s Diseas e related pathology means “having a characteristic of Alzheimer’s Disease, such as the formation of deposits containing

Aß in the brain.” The table also includes the parties’ joint constructions of claim terms proposed in the Joint Claim Constr uction Chart, ECF No. 69-1 at 3. In addition, certain minor irregularities in pr oposed claim construction language for

which the resolution was self-evident in li ght of the actual text of the claims, the parties’ filings, their presentations at oral argument, and the an alysis contained in this order, are also included within this table. 15

14 This rewriting of the claims fundamen tally altered their text, as evidenced by a serious flaw in Claims 4 and 6 -- t hose claims did not survive the rewriting process with any logical coherence. See ECF No. 75 at 38 n.5.

15 Plaintiff’s positions on claim constr uction are inconsistent, as shown by a comparison of the Joint Claim Construc tion Chart, ECF No. 69-1, and its initial brief, ECF No. 75 at 51-53, 55-62. The court has reconciled the inconsistencies by relying on both propos ed constructions proffered by plaintiff. In addition, the court confirmed with plaintiff’s couns el at oral argument that the joint

constructions contained in the Joint Clai m Construction Chart were acceptable to plaintiff. Tr. at 43. Finally, as to Claim 13’s preamble, the court finds that no

construction is needed for the term “Alzheimer’s Disease related amyloid19 IT IS SO ORDERED.

s/ Patricia E. Campbell-Smith

PATRICIA E. CAMPBELL-SMITH Judge

pathology,” as is the case for the term “Alzheimer’s Disease related amyloid accumulation” in Claim 1’s preamble.20 ATTACHMENT 1: CLAIM CONSTRUCTION TABLE

Claim # Passage to be Construed Construction

#1

Preamble A transgenic mouse with

“enhanced Alzheimer’s Disease related amyloid accumulation” in

its brain A transgenic mouse with

Alzheimer’s Disease related amyloid accumulation in its

brain at least one month

earlier in its lif e span than a mouse expressing one or no

transgenes

#1 Body “operably linked to a promoter” linked to a promoter sequence, which allows the transgene to be expressed by

the mouse

#1 Body mouse develops “accelerated deposition of Aß” in its brain as compared to non-transgenic mice or either parental mouse mouse develops deposition of

Aß in its brain at least one

month earlier in the mouse’s life span as compared to non-transgenic mice or either parental mouse

#3

Preamble A transgenic mouse with

“accelerated Alzheimer’s Disease related pathology” A transgenic mouse having a

characteristic of Alzheimer’s Disease, such as the formation of deposits containing Aß in the brain, that occurs at least

one month earlier in the mouse’s life span than in a corresponding mouse expressing only one or none of the transgenes

#3 Body “operably linked to a promoter” linked to a promoter sequence, which allows the transgene to be expressed by

the mouse

#3 Body mouse develops “accelerated deposition of Aß” in their brains as compared to non-transgenic mice or transgenic mice expressing either transgene mouse develops deposition of

Aß in their brains at least one

month earlier in the mouse’s life span as compared to non-transgenic mice or transgenic mice expressing either transgene21 #5

Preamble A transgenic mouse with

“accelerated Alzheimer’s Disease related pathology” A transgenic mouse having a

characteristic of Alzheimer’s Disease, such as the formation of deposits containing Aß in the brain, that occurs at least

one month earlier in the mouse’s life span than in a corresponding mouse expressing only one or none of the transgenes

#5 Body “operably linked to a promoter” linked to a promoter sequence, which allows the transgene to be expressed by the mouse

#5 Body “mouse develops accelerated deposition of Aß in its brain within six months of birth as compared to non-transgenic mice or transgenic mice expressing either transgene” mouse has increased deposition of Aß in its brain by its sixth month of life as compared to deposits typically found in non-transgenic mice or as compared to deposits typically found in transgenic mice expressing either

transgene

#7

Preamble A transgenic mouse with

“accelerated Alzheimer’s Disease related pathology” A transgenic mouse having a

characteristic of Alzheimer’s Disease, such as the formation of deposits containing Aß in the brain, that occurs at least

one month earlier in the mouse’s life span than in a corresponding mouse expressing only one or none of the transgenes

#7 Body “DNA sequence encoding mutant presenilin” any DNA sequence that, if made part of a mouse genome, can be caused to express a mutant form of a presenilin protein

#7 Body “operably linked to a promoter” linked to a promoter sequence, which allows the transgene to be expressed by the mouse22 #7 Body “accelerated pathol ogy develop” mouse develops (appears to be a typographic error, compare Claims 5, 8, 10, 11)

#7 Body “accelerated deposition of Aß” in its brain as compared to non-transgenic mice or transgenic mice expressing either transgene deposition of Aß in its brain at

least one month earlier in the mouse’s life span as compared to non-transgenic mice or transgenic mice expressing either transgene

#8

Preamble “elevated levels of amyloidogenic Aß (Aß42(43)) as a pathology for

Alzheimer’s Disease” No construction needed

#8 Body “DNA sequence encoding mutant presenilin” any DNA sequence that, if made part of a mouse genome, can be caused to express a mutant form of a presenilin protein

#8 Body “operably linked to a promoter” linked to a promoter sequence, which allows the transgene to be expressed by the mouse

#8 Body mouse develops “accelerated deposition of Aß (Aß42(43))” in its brain as compared to non-transgenic mice or transgenic mice expressing either transgene mouse develops deposition of Aß (Aß42(43)) in its brain at

least one month earlier in the mouse’s life span as compared to non-transgenic mice or transgenic mice expressing either transgene

#9

Preamble “elevated levels of amyloidogenic Aß (Aß42(43)) as a pathology for

Alzheimer’s Disease” No construction needed

#9 Body “operably linked to a promoter” linked to a promoter sequence, which allows the transgene to be expressed by the mouse23 #10 Body “DNA sequence encoding mutant presenilin” any DNA sequence that, if made part of a mouse genome, can be caused to express a mutant form of a presenilin protein

#10 Body “operably linked to a promoter” linked to a promoter sequence, which allows the transgene to be expressed by the mouse

#10 Body mouse develops “accelerated deposition of Aß” in its brain as compared to non-transgenic mice or either parental mouse mouse develops deposition of

Aß in its brain at least one

month earlier in the mouse’s life span as compared to non-transgenic mice or either parental mouse

#11

Preamble “elevated levels of amyloidogenic Aß (Aß42(43)) as a pathology for

Alzheimer’s Disease” No construction needed

#11 Body “DNA sequence encoding mutant presenilin” any DNA sequence that, if made part of a mouse genome, can be caused to express a mutant form of a presenilin protein

#11 Body “operably linked to a promoter” linked to a promoter sequence, which allows the transgene to be expressed by the mouse

#11 Body mouse develops “accelerated deposition of Aß (Aß42(43))” in their brains as compared to non-transgenic mice or either parental mouse mouse develops deposition of Aß (Aß42(43)) in their brains

at least one month earlier in the mouse’s life span as compared to non-transgenic mice or either parental mouse24 #13

Preamble a transgenic mouse with “enhanced

Alzheimer’s Disease related amyloid pathology” a transgenic mouse with

Alzheimer’s Disease related amyloid pathology that occurs

at least one month earlier in the mouse’s life span than a corresponding mouse expressing only one or none of the transgenes

#13 Body “operably linked to a promoter” linked to a promoter sequence, which allows the transgene to be expressed by the mouse

#13 Body mouse develops “accelerated deposition of AD” in its brain as compared to non-transgenic mice or either parental mouse mouse develops deposition of

Aß in its brain at least one

month earlier in the mouse’s life span as compared to non-transgenic mice or either parental mouse