Opinion
Case No. 1:20-cv-274
2021-03-04
IMMUNOGEN, INC., Plaintiff, v. Andrei IANCU, Defendant.
Craig Crandall Reilly, Law Office of Craig C. Reilly, Alexandria, VA, John Christopher Rozendaal, Sterne, Kessler, Goldstein & Fox PLLC, Washington, DC, for Plaintiff. Matthew J. Mezger, Dennis Carl Barghaan, Jr., United States Attorney's Office, Alexandria, VA, for Defendant.
Craig Crandall Reilly, Law Office of Craig C. Reilly, Alexandria, VA, John Christopher Rozendaal, Sterne, Kessler, Goldstein & Fox PLLC, Washington, DC, for Plaintiff.
Matthew J. Mezger, Dennis Carl Barghaan, Jr., United States Attorney's Office, Alexandria, VA, for Defendant.
MEMORANDUM OPINION
T. S. Ellis, III, United States District Judge Plaintiff ImmnuoGen, Inc. brought this 35 U.S.C. § 145 action following the Patent Trial and Appeal Board's ("PTAB") decision affirming an examiner's rejection of all pending claims in plaintiff's U.S. Patent Application Serial No. ’14/509,809 (the "’809 Application"). In the ‘809 Application, plaintiff seeks to patent a dosing method for treating patients with certain ovarian or peritoneal cancers using a class of antibody-drug conjugates that include IMGN853 at a dose of 6 milligrams per kilogram of adjusted ideal body weight ("AIBW"). A patent examiner and the PTAB rejected all of plaintiff's claims in the ’809 Application on two grounds: (i) that the ‘809 Application is unpatentable under 35 U.S.C. § 103 ; and (ii) that the ‘809 Application is unpatentable under the doctrine of obviousness-type double patenting.
Obviousness-type double patenting is a court-created doctrine that is grounded in Section 101 of the Patent Act. See Abbvie v. Mathilda and Terence Kennedy Inst. of Rheumatology Trust , 764 F.3d 1366, 1372 (Fed. Cir. 2014).
Following the PTAB's rejection of the ‘809 Application, plaintiff filed this § 145 action contesting the PTAB's ruling and, as the law allows, provided expert reports as part of discovery in this litigation. Also, as the law allows, Defendant Andrei Iancu's answer raised the additional ground for the rejection of the ‘809 Application – a ground not previously relied upon by the PTAB – that the ‘809 Application is unpatentable because its claims are fatally indefinite. See 35 U.S.C. § 112.
Defendant is sued in his official capacity as the Director of the USPTO.
At issue now, on defendant's motion for summary judgment are the following issues: (i) whether ‘809 Application's claims are fatally indefinite under 35 U.S.C. § 112(b) ; (ii) whether ‘809 Application's claims are obvious such that they are unpatentable under 35 U.S.C. § 103 ; and (iii) whether ‘809 Application's claims are unpatentable under the obviousness-type double patenting doctrine. See Abbvie , 764 F.3d at 1372. The parties have fully briefed these issues and oral argument on the motion was heard telephonically on January 5, 2021, focusing chiefly on the indefiniteness issue. Because defendant's motion has been fully briefed and argued orally, it is now ripe for disposition. For the reasons that follow, defendant's motion for summary judgment must be granted.
I.
Summary judgment is appropriate only where there are no genuine disputes of material fact. See Rule 56, Fed. R. Civ. P. To this end, defendant, pursuant to Rule 56 and Local Rule 56, set forth a statement of material facts that defendant contends are undisputed. Plaintiff then, as required by Rule 56 and Local Rule 56, responded to defendant's statement of material facts and supporting any alleged disputes of fact with admissible evidence. Plaintiff also set forth a set of "Disputed Material Facts Precluding Summary Judgment." Neither the Federal Rules nor the Local Rules invite, permit, or forbid plaintiff, or any nonmovant, from setting forth the nonmovant's enumeration of disputed facts. In this case, plaintiff's inclusion of plaintiff's alleged Disputed Statement of Facts does not alter the focus of the summary judgment analysis, which remains the movant's statement of undisputed facts and the nonmovant's response to those facts, for it is from this statement of undisputed facts and the nonmovant's response that a district court determines whether genuine issues of fact are disputed.
Plaintiff cites Metric/Kvaerner Fayetteville v. Fed. Ins. Co. , 403 F.3d 188, 197 (4th Cir. 2005) at the beginning of plaintiff's statement of "Disputed Material Facts Precluding Summary Judgment." Opp'n at 15 (Dkt. 56). Yet, this case does not sanction or authorize a nonmovant to include its own statement of disputed material facts.
Accordingly, the following statement of facts is derived from a careful review of defendant's statement of undisputed facts, the nonmovant's response, and the record.
1. Plaintiff is the assignee of the ‘809 Application, which claims the benefit of the filing date of a provisional application filed on October 8, 2013.
2. As the parties agree, the ’809 Application concerns methods of treating patients having ovarian cancer or cancers of the peritoneum that express folate receptor 1 ("FOLR1") with a specific type of immunoconjugate.
3. More specifically, the ‘809 Application claims methods of treating a patient with FOLR1-expressing ovarian cancer or cancer of the peritoneum by administering an immunoconjugate that comprises an antibody or antibody fragment that binds to FOLR1, a chemical linker, and a maytansinoid drug.
4. Each of the independent claims of the ’809 Application in this litigation also requires administering immunoconjugate to the patient "at a dose of 6 milligrams (mg) per kilogram (kg) of adjusted ideal body weight (AIBW) of the patient."
5. An immunoconjugate is a composition containing an antibody or the antigen-binding portion of an antibody coupled to a drug by a chemical linker. Immunoconjugates are designed to bind to a cell or cells of interest and to deliver a drug payload to that specific cell or cells. Immunoconjugates are also known as antibody-drug-conjugates, or sometimes as "ADCs."
6. Specifically, independent claims 1, 317, and 341 of the ‘809 Application read as follows:
a. 1. A method for treating a human patient having an FOLR1-expressing cancer or cancer of the peritoneum comprising administering to the patient an immunoconjugate which binds to FOLR1 polypetide,
Wherein the immunoconjugate comprises an antibody or antigen-binding fragment thereof that comprises the variable light chain (VL) complementarity determining region (CDR)-1, VH CDR-2, VL CDR-3, variable heavy chain (VH) CDR-1, VH CDR-2, and VH CDR-3 of SEQ. ID Nos.: 6-9, 11, and 12, respectively, and a maytansinoid, and
Wherein the immunoconjugate is administered at a dose of 6 milligrams (mg) per kilogram (kg) of adjusted ideal body weight (AIBW) of the patient.
b. 317. A method for treating a human patient having an FOLR1-expressing ovarian cancer comprising administering intravenously to the patient an immunoconjugate at a dose of 6 milligrams
Maytansinoids constitute a class of antitumor agent drugs, derived from the chemical maytansine.
(mg) per kilogram (kg) of adjusted ideal body weight (AIBW) of the patient
Wherein the immunoconjugate comprises DM4 and an antibody comprising (i) a heavy chain comprising the same amino acid sequence as the amino acid sequence of the heavy chain encoded by the plasmid deposited with the American Type Culture Collection (ATCC) as PTA-10772 and (ii) a light chain comprising the same amino acid sequence as the amino acid sequence of the light chain encoded by the plasmid deposited with the ATCC as PTA-10774, and
Wherein the DM4 is linked to the antibody by sulfo-SPDB.
c. 341. A method for treating a human patient having an FOLR1-expressing cancer of the peritoneum comprising administering intravenously to the patient an immunoconjugate at a dose of 6 milligrams (mg) per kilogram (kg) of adjusted ideal body weight (AIBW) of the patient
Wherein the immunoconjugate comprises DM4 and an antibody comprising (i) a heavy chain comprising the same amino acid sequence as the amino acid sequence of the heavy chain encoded by the plasmid deposited with the American Type Culture Collection (ATCC) as PTA-10772 and (ii) a light chain comprising the same amino acid sequence as the amino acid sequence of the light chain encoded by the plasmid deposited with the ATCC as PTA-10774, and
Wherein the DM4 is linked to the antibody by sulfo-SPDB.
7. Claims 1, 317, and 341 are "independent" claims, while the remaining claims are "dependent" because they incorporate by reference all of the limitations recited in their respective independent claims. These dependent claims differ from the independent claims in that they recite a specific route of administration, a specific frequency of administration, a specific cancer to be treated, a specific linker, a specific maytansinoid, or a specific antibody or antibody fragment.
8. IMGN853 is an embodiment of the recited immunoconjugates.
9. In the "Definitions" section of the ’809 Application, the term "ideal body weight" or "IBW" is defined as
"an estimate of weight corrected for sex and height, and optionally frame size."
10. In the same definition, it is explained that
"IBW can be calculated, for example, using the formulas IBW = 0.9H-88 (for males) and IBW = .9H-92 (for females), wherein H = height in cm."
11. Also, in the "Definitions" section of the ’809 Application, the term "adjusted ideal body weight" (AIBW) or "adjusted body weight" (ADJ) refers to
"a size descriptor that accounts for sex, total body weight, and height."
12. In the same definition, it is explained that
"AIBW (ADJ) can be calculated, for example, using the formula ADJ = IBW + 0.4(weight in kg – IBW)."
13. Later, the ’809 Application includes a list of examples. The examples are prefaced with the explanation that "[i]t is understood that the examples and embodiments described
herein are for illustrative purposes only and that various modifications or changes in light thereof will be suggested to persons skilled in the art and are to be included within the spirit and purview of this application."
14. In Example 4 of the ‘809 Application, IBW is defined as follows
a. IBW (male) = 0.9H-88
b. IBW (female) = 0.9H-92
15. Similarly, Example 4 of the ‘809 Application defines AIBW is defined as follows
a. AIBW = IBW + 0.4(Actual weight in kg – IBW).
16. The ’809 Application recognizes, as plaintiff admits, that "IMGN853 has previously been described in International Published Application Nos. WO 2011/106528 ["Ab ’528"], WO 2012/135675 ["Carrigan ’675"], and WO 2012/138749, and U.S. Published Application Nos. 2012/0009181 ["Ab ’181"], 2012/0282175 ["Carrigan ’175"], and 2012/0282282 ["Lutz ’282"].
17. The PTAB rejected claims 1, 230, 237, 238, 242, 252-255, 258-266, 300, 317-325, 329, 330, 341-349, and 354 of the ‘809 Application as obvious under 35 U.S.C. § 103 over the combined teachings of Lutz ’282, Ab ’528, Ab ’181, Armstrong et al., European Journal of Cancer Supplements , 7:450, Abstract 8000 (2009) ("Armstrong"), Bruce Green & Stephen B. Duffull, Brit. J. Clinical Pharm. 58:119-33 (2004) ("Green"), Geraghty et al. , US 2009/0162374 Al ("Geraghty"), Fuchs et al. , US 2012/148577 Al ("Fuchs"), and Narain et al. US 2014/0302014 ("Narain").
18. The immunoconjugate recited in the claims of the ‘809 Application was known in the art prior to October 8, 2013, as was a method of using that immunoconjugate to treat the cancers recited in claim 1 of the ‘809 Application.
19. The ’809 Application recognizes, as plaintiff admits, that the claimed immunoconjugate "has been previously described" in Ab ’528 (for which plaintiff is the applicant), Carrigan ’675, Ab ’181, Carrigan ’175, and Lutz ‘282.
20.Ab ’528 discloses an immunoconjugate within the scope of Plaintiff's claims in the ’809 Application. Ab ’528 describes the huMOV19-sulfo-SPDB-DM4 and huMOV19-SPDB-DM4 immunoconjugates.
Plaintiff disputes the asserted basis for the PTAB's rejection of the ‘809 Application, arguing that, in this litigation, defendant abandoned all of the grounds of rejection in the PTAB's final decision and, in particular, defendant abandoned reliance on Narain. But plaintiff does not dispute the asserted fact that the PTAB relied on Narain as part of the basis for the PTAB's rejection of the ‘809 Application. Accordingly, there is no dispute of the fact that the PTAB relied on Narain in its final decision. Moreover, defendant asserts that it simply moved from relying on Narain, which discussed using AIBW dosing for an anti-cancer drug (busulfan) to relying directly on the prior art busulfan label. See Def. Reply at 4 n.2.
Plaintiff objects to the asserted fact "to the extent the [Defendant] is suggesting that this signifies that the claims would have been obvious." Opp'n at 8. But importantly, plaintiff does not dispute or deny that the immunoconjugate recited in the claims of the ‘809 Application was known in the art prior to October 8, 2013, as was a method of using that immunoconjugate to treat the cancers recited in claim 1 of the ‘809 Application. Plaintiff only attempts to dispute the legal consequences of this fact, but not the fact itself.
These immunoconjugates contain an anti-FOLRl antibody or antibody fragment (i.e., huMOV19) coupled to a maytansinoid (i.e., DM4) by a sulfo-SPDB linker or SPDB linker, respectively. The huMOV19 antibody is humanized anti-FOLRl antibody encoded by the plasmid deposited by Ab with the ATCC under, for example, the ATCC Accession No. PTA-10774. Independent claims 317 and 341 of the ‘809 Application expressly recite an immunoconjugate wherein the antibody or antibody fragment is encoded by the plasmid having ATCC Accession No. PTA-10774.
21. Ab ’528 also teaches that the huMOV19-sulfo-SPDB-DM4 immunoconjugate shows promise for treating cancer. Specifically, it discloses in vivo experiments using the huMOV19-sulfo-SPDB-DM4 immunoconjugate to inhibit ovarian tumor growth in three different mouse models, wherein the mouse ovarian tumors express FOLR1 at levels comparable to those found in human ovarian tumors. Ab ’528 reports that the huMOV19-sulfo-SPDB-DM4 immunoconjugate provides "strong anti-tumor activity."
22. In terms of dosing, Ab ’528 discloses that one "can easily determine optimum dosages, dosing methodologies, and repetition rates. In certain embodiments, dosage from .01 µg to 100 mg per kg of body weight." In other, the dose is "from about 0.1 mg to about 20 mg per kg of body weight."
23. Ab '181 likewise reports "strong anti-tumor activity" for the huMOV19-sulfo-SPDB-DM4 immunoconjugate in in vivo experiments using the same models. It also discloses that the huMOV19-sulfo-SPDB-DM4 immunoconjugate may be administered at "from 0.01µg-100mg/kg" and that one "can easily determine optimum dosages, dosing methodologies and repetition rates." Both Ab ‘528 and Ab '181 define cancers capable of treatment with this immunoconjugate as including cancers of the peritoneum.
24. Plaintiff has now received US patent 8,557,966 based on the application that published as Ab '181.
Humanized antibodies are antibody molecules from non-human species that have been genetically engineered to retain their antigen-binding specificity but modified to make the antibody molecules less immunogenic when administered to human patients.
Plasmids are small, circular, extrachromosal DNAs that are often used in the laboratory to manipulate and clone genes.
Plaintiff again admits the asserted fact but attempts to dispute any suggestion that the fact signifies obviousness. As discussed supra , there is no genuine dispute of material fact where plaintiff admits the substance of the asserted fact.
Plaintiff again admits the asserted fact but attempts to dispute any suggestion that the fact signifies obviousness. As discussed supra , there is no genuine dispute of material fact where plaintiff admits the substance of the asserted fact.
Plaintiff again admits the asserted fact but attempts to dispute any suggestion that the fact signifies obviousness. As discussed supra , there is no genuine dispute of material fact where plaintiff admits the substance of the asserted fact.
25. Plaintiff is the applicant for Carrigan ‘675.
26. Carrigan ‘675 similarly discloses treating ovarian cancer by administering the same huMOV19-sulfo-SPDB-DM4 immunoconjugate taught in Ab ‘528 and Ab '181, which Carrigan ‘675 refers to as IMGN853. Like the two Ab references, Carrigan ‘675 also discloses the results of in vivo experiments using the IMGN853 immunoconjugate to inhibit ovarian tumor growth in animal models. Carrigan ‘675's IMGN853 immunoconjugate is the same immunoconjugate described and claimed in the ‘809 Application.
27. Carrigan ’675 discloses that suitable doses for IMGN853 can range from 0.01µg to 100 mg/kg of body weight in some embodiments and from 0.1µg to 20 mg/kg in other embodiments. Carrigan ’675 further discloses that IMGN853 can be administered once or more daily, weekly, monthly, or yearly. And Carrigan ’675 also advises that one "can easily determine optimum dosages, dosing methodologies, and repetition rates."
28. Plaintiff is the assignee for Lutz ‘282.
29. Around the same time that Ab '181, Ab ‘528, Carrigan ‘175 and Carrigan ‘675 were published, Lutz ‘282 reported the results of studies in rabbit models examining whether the ocular toxicity often observed with immunoconjugates containing the drug DM4 could be reduced by adding charged groups to the immunoconjugate's chemical linker.
30. One of the immunoconjugates studied by Lutz ‘282 was the huMOV19-sulfo-SPDB-DM4 (i.e. IMGN853).
31. In terms of immunoconjugate dosing, Lutz ‘282 focuses on doses around 6mg/kg based on total body weight:
In one embodiment, the dose of [antibody drug conjugate] administered is at least about 4 mg/kg. In another embodiment, the dose is between 4 mg/kg and 16 mg/kg. In another embodiment, the dose is between about 4 mg/kg and about 8 mg/kg. In another embodiment, the dose is between 5 mg/kg and 6 mg/kg. In another embodiment, the dose is between about 6 mg/kg and 8 mg/kg. In a further embodiment, the dose is between 6 mg/kg and about 7 mg/kg. In another embodiment, the dose is between about 7 mg/kg and about 8 mg/kg. In yet another embodiment, the dose is between about 4 mg/kg and 6 mg/kg.
32. In May/June of 2013, which is prior to the priority date of the ’809 Application of October 8, 2013, ImmunoGen researchers presented an
Plaintiff again admits the fact that Carrigan ’675 discloses certain dosing for IMGN853 and that Carrigan ’675 advises that one "can easily determine optimum dosages, dosing methodologies, and repetition rates, but attempts to dispute any suggestion that this fact signifies obviousness. Thus, plaintiff argues only the legal consequences of the fact but not the truth of the asserted fact.
Plaintiff again admits the asserted fact but attempts to dispute any suggestion that the fact signifies obviousness. Thus, there is no genuine dispute of material fact.
Plaintiff admits that the quote appears in Lutz ’282 but asserts that the fact is "otherwise denied" with a reference to plaintiff's asserted disputed facts. Because plaintiff admits that the quote is appropriately attributed and accurately quoted, there is no genuine dispute of material fact as to the asserted Lutz ’282 quote.
abstract reporting "results" from Phase I testing of IMGN853 on human patients at a conference. The abstract reports that, at doses of 3.3 mg IMGN853 per kilogram total body weight, "one patient with serious [epithelial ovarian cancer ] had an 82% reduction in CA125 (confirmation pending." As the ’809 Application notes, a "decrease in CA125 level over time is indicative of therapeutic efficacy." The abstract concludes that "dose escalation is ongoing."
33. Dosing based on IBW or AIBW was well known known prior to October 8, 2013. It was also known that failure to adjust doses could lead to possible negative outcomes. Green discloses that dosing based on AIBW helps normalize the volume of distribution. Geraghty similarly teaches dosing according to AIBW or actual body weight (whichever is lower) when administering compositions for the treatment of autoimmune and alloimmune diseases. Fuchs likewise discloses the use of dosing according to AIBW or actual body weight (whichever is lower) when administering cyclophosphamide.
34. There were at least eleven formulas for calculating IBW known in the art as of October 8, 2013. There were also multiple adjustment factors that could then be used to calculate AIBW.
35. The examiner found that the huMOV19-sulfo-SPDB-DM4 immunoconjugate disclosed in Lutz ‘282, Ab ‘528, Ab '181, Carrigan ‘675 and Carrigan ‘175 is the same immunoconjugate identified in the ‘809 Application.
36. The examiner found that the only difference between the claimed methods and Lutz ’282 or Carrigan ’675 and ’175, "if any, is determining the dose by using AIBW."
37. The examiner also found that it would have been prima facie obvious to a skilled artisan in October 2013 to dose the claimed immunoconjugates based on AIBW given that "physicians used AIBW when administering a variety of drugs" to patients.
Plaintiff again admits the asserted fact but attempts to dispute any suggestion that the fact signifies obviousness. Thus, there is no genuine dispute of material fact.
Plaintiff again admits the asserted fact but denies that AIBW has ever been used for dosing a therapy in the relevant field or with respect to doing a general population as opposed to an overweight population. Those facts are not asserted by defendant, however. Accordingly, there is no genuine dispute of material fact that dosing based on AIBW and IBW was known in the prior art.
Plaintiff again admits the asserted fact but makes arguments about the legal consequence of the asserted fact. Thus, there is no genuine dispute of material fact.
Plaintiff admits that the asserted fact is what the examiner found but argues that the examiner was incorrect and the finding unsupported. Because the asserted fact – that is that the examiner found certain information – is undisputed, there is no genuine dispute of material fact with respect to the asserted fact.
Plaintiff admits that the asserted fact is what the examiner found but argues that the examiner was incorrect and the finding unsupported. As discussed supra , because the asserted fact – that is that the examiner found certain information – is undisputed, there is no genuine dispute of material fact with respect to the asserted fact.
Plaintiff admits that the asserted fact is what the examiner found but argues that the examiner was incorrect and the finding unsupported. As discussed supra , because the asserted fact – that is that the examiner found certain information – is undisputed, there is no genuine dispute of material fact with respect to the asserted fact.
38. Moreover, the examiner found that a skilled artisan would have been motivated to use AIBW dosing for the claimed immunoconjugate given Ab '181's disclosure that one can readily determine the optimum dosages.
39. Finally, the examiner found the claims in the ‘809 Application invalid for obviousness-type double patenting over the claims in US Patent Nos. (i) 8,557,966; (ii) 9,133,275; (iii) 9,598,490; and (iv) 9,670,280.
40. The PTAB affirmed the examiner's rejection, finding that "the prior art teaches the use of anti-FOLRl immunoconjugate, within the scope of [Plaintiff's] claimed invention, to treat FOLR1-expressing ovarian cancer, using the art recognized AIBW based dosing regimen that is optimized by an administering physician."
41. The PTAB found that plaintiff's claim 1 of the ’809 Application "recites a combination of elements that were all known in the prior art, and all that was required to obtain that combination was to substitute one well-known dosing method for another."
42. The PTAB was not persuaded by plaintiff's rebuttal argument that the claimed AIBW dosing methods in the ‘809 Application are not obvious because they allegedly provide the unexpectedly superior result of solving IMGN853-based ocular toxicity.
43. The PTAB found that adjusting the immunoconjugate dosage to maximize benefit while reducing negative side effects is not a patentable distinction explaining that, "where, as here, the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." The PTAB emphasized the prior art's teachings that one "can easily determine
Plaintiff admits that the asserted fact is what the examiner found but argues that the examiner was incorrect and the finding unsupported. As discussed supra , because the asserted fact – that is that the examiner found certain information – is undisputed, there is no genuine dispute of material fact with respect to the asserted fact.
Plaintiff admits that the asserted fact is what the examiner found but argues that the examiner was incorrect and the finding unsupported. As discussed supra , because the asserted fact – that is that the examiner found certain information – is undisputed, there is no genuine dispute of material fact with respect to the asserted fact.
Plaintiff admits that the asserted fact is what the PTAB found but argues that the PTAB was incorrect and the finding unsupported. Because the asserted fact – that is that the PTAB found certain information – is undisputed, there is no genuine dispute of material fact with respect to the asserted fact.
Plaintiff admits that the asserted fact is what the PTAB found but argues that the PTAB was incorrect and the finding unsupported. As discussed supra , because the asserted fact – that is that the PTAB found certain information – is undisputed, there is no genuine dispute of material fact with respect to the asserted fact.
Plaintiff admits that the asserted fact is what the PTAB found but argues that the PTAB was incorrect and the finding unsupported. As discussed supra , because the asserted fact – that is that the PTAB found certain information – is undisputed, there is no genuine dispute of material fact with respect to the asserted fact.
optimum dosages, dosing methodologies, and repetition rates."
44. The PTAB also affirmed the examiner's rejection of plaintiff's claims in the ‘809 Application for obviousness-type double patenting over the claims of plaintiff's U.S. patents Nos. (i) 8,557,966; (ii) 9,133,275; (iii) 9,598,490; and (iv) 9,670,280.
45. The Board found that, because plaintiff did not "separately argue its claims," claim 1 of the ‘809 Application would be treated as representative of all the claims.
46. As permitted as part of this § 145 litigation, the parties submitted additional evidence. Plaintiff produced the expert reports of Dr. Dhaval K. Shah and Dr. Anthony W. Tolcher. Defendant produced one expert report by Dr. William D. Figg who opined: (i) that the PTAB had correctly found the claims of the ‘809 Application obvious and invalid for obviousness-type double patenting and (ii) that a skilled artisan would not have a reasonable certainty as to the meaning of the term AIBW as recited in plaintiff's claims.
Plaintiff admits that the asserted fact is what the PTAB found but argues that the PTAB was incorrect and the finding unsupported. As discussed supra , because the asserted fact – that is that the PTAB found certain information – is undisputed, there is no genuine dispute of material fact with respect to the asserted fact.
Plaintiff admits that the asserted fact is what the PTAB found but argues that the PTAB was incorrect and the finding unsupported. As discussed supra , because the asserted fact – that is that the PTAB found certain information – is undisputed, there is no genuine dispute of material fact with respect to the asserted fact.
Plaintiff admits that the asserted fact is what the PTAB found but argues that the PTAB was incorrect and the finding unsupported. As discussed supra , because the asserted fact – that is that the PTAB found certain information – is undisputed, there is no genuine dispute of material fact with respect to the asserted fact.
II.
Defendant has moved for summary judgment on three grounds: (i) plaintiff's claims are indefinite as a matter of law; (ii) plaintiff's claims would have been obvious based on the prior art; and (iii) plaintiff's claims are invalid as a matter of law as obviousness-type double patenting. The standard for summary judgment is too well-settled to require extensive discussion here. Simply put, summary judgment is appropriate when there is "no genuine issue as to any material fact" and based on those undisputed facts the moving party "is entitled to judgment as a matter of law." Celotex Corp. v. Catrett , 477 U.S. 317, 322, 106 S.Ct. 2548, 91 L.Ed.2d 265 (1986). To serve as a bar to summary judgment, facts must be "material," which means that the disputed fact "might affect the outcome of the suit under the governing law." Anderson v. Liberty Lobby, Inc. , 477 U.S. 242, 248, 106 S.Ct. 2505, 91 L.Ed.2d 202 (1986). Importantly, at the summary judgment stage, courts must "view the evidence in the light most favorable to ... the non-movant." Dennis v. Columbia Colleton Med. Ctr., Inc. , 290 F.3d 639, 645 (4th Cir. 2002).
III.
Defendant first argues that plaintiff's claims are fatally indefinite because the ‘809 Application does not establish with adequate specificity how to calculate IBW and AIBW in a way that would provide a skilled artisan with reasonable certainty as to the scope of the claimed invention. Plaintiff disagrees, arguing that there are issues of fact concerning whether the ‘809 Application is fatally indefinite and whether a skilled artisan would lack reasonable certainty concerning the calculation of AIBW in the context of the ‘809 Application.
The Patent Act requires that a patent specification "conclude with one or more claims particularly pointing and distinctly claiming the subject matter which the applicant regards as [the] invention." 35 U.S.C. § 112 (emphasis added). The Supreme Court, applying § 112, has held that "a patent must be precise enough to afford clear notice of what is claimed, thereby ‘appris[ing] the public of what is still open to them.’ " Nautilus, Inc. v. Biosig Instruments, Inc. , 572 U.S. 898, 909, 134 S.Ct. 2120, 189 L.Ed.2d 37 (2014) (quoting Markman v. Westview Instruments, Inc. , 517 U.S. 370, 373, 116 S.Ct. 1384, 134 L.Ed.2d 577 (1996) ). Moreover, the Supreme Court in Nautilus instructs that "a patent is invalid for indefiniteness if its claims, read in light of the specification delineating the patent, and the prosecution history, fail to inform, with reasonable certainty, those skilled in the art about the scope of the invention." Id. at 901, 134 S.Ct. 2120 (citing 35 U.S.C. § 112(b) ).
In accordance with Nautilus , the Federal Circuit has held that the "[r]easonable certainty" standard does not require "absolute or mathematical precision." Biosig Instruments, Inc. v. Nautilus, Inc. , 783 F.3d 1374, 1381 (Fed. Cir. 2015) (internal quotation marks omitted). But an application's language should not be "treated as meaningless." Bicon, Inc. v. Straumann Co. , 441 F.3d 945, 951 (Fed. Cir. 2006) ; Playtex Prods., Inc. v. Procter & Gamble Co. , 400 F.3d 901, 908 (Fed. Cir. 2005) (rejecting the district court's construction of the claim because it "reads out the essence of the claim limitation ‘substantially flattened’ as it equates ‘flattened’ with ‘flat’ "). Importantly, the Federal Circuit instructs district courts to evaluate first the language of a claim to determine whether a disputed term is reasonably clear. See Berkheimer v. HP Inc. , 881 F.3d 1360, 1363 (Fed. Cir. 2018) ("We look first to the language of the claim to determine whether the meaning of [the term] is reasonably clear."). Next, the Federal Circuit instructs district courts to look at pertinent intrinsic evidence and, then, to extrinsic evidence. See HZNP Medicines LLC v. Actavis Labs. UT, Inc. , 940 F.3d 680 (Fed. Cir. 2019).
A.
As an initial matter, it is appropriate to note that the PTAB and the patent examiner did not rely on indefiniteness as a basis for rejecting the ’809 Application. Nonetheless, the parties correctly agree that defendant can raise "new grounds for rejecting a § 145 plaintiff's claims on the merits in response to new evidence presented" and may "raise an affirmative defense for the district court to consider." Hyatt v. Iancu , 332 F. Supp. 3d 113, 120 (D.D.C. 2018). As the Supreme Court has recognized, § 145 permits parties "to present to the court evidence" that was not presented in the administrative process. Dickinson v. Zurko , 527 U.S. 150, 164, 119 S.Ct. 1816, 144 L.Ed.2d 143 (1999). Indeed, the Federal Circuit has recognized that § 145 proceedings are "expansive" permitting the parties to "conduct discovery and introduce new evidence." Nantkwest, Inc. v. Iancu , 898 F.3d 1177, 1180 (Fed. Cir. 2018). It is therefore appropriate to consider defendant's indefiniteness argument, even though this argument was not raised in the patent prosecution process or decided by the PTAB.
B.
Defendant's indefiniteness argument focuses on the lack of any limitation on, or specification regarding, the calculation of AIBW in the ‘809 Application. This focus is appropriate inasmuch as the Definitions section of the ’809 Application states that AIBW can be calculated "for example , using the formula ADJ = IBW +.4(weight in kg-IBW)." Exh. 3, at A26, ¶ 71 (emphasis added). Thus, in using the phrase "for example" the ’809 Application makes clear that there are multiple ways to calculate AIBW and therefore ’809 Application leaves a skilled artisan to wonder or to guess whether the formula provided is the only one covered by the ’809 Application.
Nor is this the only source of indefiniteness in the ’809 Application. The definition of IBW in the ’809 Application – from which AIBW calculation is derived – adds more uncertainty. IBW is defined as "an estimate of weight corrected for sex and height, and optionally frame size" that can be calculated "for example , using the formulas IBW = 0.9H-88 (for males) and IBW = 0.9H-92 (for females)." Exh. 3, at A25, ¶ 69 (emphasis added). Thus, the definition of IBW also makes clear that the formulas included for IBW are but examples of possible methods of calculating IBW and that a calculation of IBW may optionally account for frame size in an unspecified manner, thus further broadening the realm of possible formulas for IBW.
Further disclosing the indefiniteness of the meaning of IBW and AIBW in the context of the ‘809 Application is the statement in the application that
IBW, LBW [lean body weight] are discussed in more detail in Green and Duffull, British Journal of Clinical Pharmacology 58: 119-133 (2004), which is herein incorporated by reference in its entirety.
Exh. 3, A26 ¶ 72. Green, which is included in the administrative record, provides multiple ways to calculate IBW and multiple correction factors that may be used for AIBW. See A4000-4001. Thus, the ‘809 Application specifically incorporates multiple possible formulas that may be used to calculate IBW and AIBW and thereby preventing a skilled artisan from discerning the scope of the claim with the requisite reasonable certainty. See Nautilus , 572 U.S. at 901, 134 S.Ct. 2120. Accordingly, as Nautilus teaches, a person skilled in the art would lack reasonable certainty about the scope of the ‘809 Application because the ’809 Application provides no limiting or defining guidance on the calculation of AIBW, an element upon which each of the independent claims rests.
Seeking to avoid this conclusion, plaintiff attempts to ignore and therefore render meaningless the "for example" and "optionally" language from the ’809 Application. Plaintiff's attempt fails. To begin with, the Federal Circuit has previously declined to "cull out a single ‘e.g.’ phrase from a lengthy written description to serve as the exclusive definition of a facially subjective term." Interval Licensing LLC v. AOL, Inc. , 766 F.3d 1364, 1373 (Fed. Cir. 2014). Indeed, in Interval , the Federal Circuit held that "a person of ordinary skill in the art would not understand the ‘e.g.’ of the phrase to constitute an exclusive definition." Id. at 1374. So too, here, a person of ordinary skill in the art would not understand the "for example" in the ’809 Application to constitute an exclusive formula for calculating IBW or AIBW.
In a more recent case, IQASR LLC v. Wendt Corp. , 825 F. App'x 900 (Fed. Cir. 2020), the Federal Circuit rejected a claim as indefinite where there were "multiple layers of definitions" that were all "open-ended and non-limiting," such that a "skilled artisan must wade through a morass of uncertainty and contradiction to get to this point." Id. As in the IQASR case, there are here multiple possible formulas for calculating AIBW and IBW and a skilled artisan would have to "wade through" that morass to determine which one was covered under the scope of the ‘809 Application. Id.
Particularly pertinent on the indefiniteness issue is Teva Pharms. USA, Inc. v. Sandoz, Inc. , 789 F.3d 1335, 1345 (Fed. Cir. 2015). There, the Federal Circuit found claims indefinite where the claims required a specific measurement or calculation, and more than one measurement or calculation method could be used, but the patent provided no guidance on which was to be used. In Teva , the Federal Circuit determined that where the claim included a specific measurement of a "molecular weight" of a claimed copolymer and the specification did not indicate which of three measurement methods used in the industry was intended in the patent, and thus the claim was fatally indefinite. Teva , 789 F.3d at 1345. Because it was unclear in Teva which measurement to use for the claimed molecular weight and those different measurements would yield different results, the claim "failed to inform with reasonable certainty those skilled in the art about the scope of the invention." Id. Similarly, here as in Teva , there are several available formulas for calculating AIBW and the ‘809 Application fails to inform a skilled artisan of the scope of the proposed invention with reasonable certainty.
See also Honeywell Int'l Inc. v. ITC , 341 F.3d 1332, 1339–40 (Fed. Cir. 2003).
Plaintiff next points to Example 4 as limiting the scope of the ‘809 Application to the calculation used in that example. This argument is also unavailing. To begin with, the ‘809 Application specifically denies that the examples limit the scope of the claims included in the application. In this regard, the ‘809 Application states:
It is understood that the examples and embodiments described herein are for illustrative purposes only and that various modifications or changes in light thereof will be suggested to persons skilled in the art and are to be included within the spirit and purview of this application.
Exh. 3, A56, ¶ 181. In any event, the Federal Circuit has made clear that "as a general rule claims of a patent are not limited to the preferred embodiment ... or to the examples listed within the patent specification." Glaxo Wellcome, Inc. v. Andrx Pharm., Inc. , 344 F.3d 1226, 1233 (Fed. Cir. 2003). Indeed, "even if a specification has only one embodiment, its claims will not be confined to that example." Aria Diagnostics, Inc. v. Sequenom, Inc. , 726 F.3d 1296, 1301 (Fed. Cir. 2013). Thus, both settled precedent and the ‘809 Application itself preclude plaintiff from relying on Example 4 to limit the scope of the claims.
Finally, plaintiff argues that indefiniteness may not be decided on summary judgment because there is a factual dispute over whether a skilled artisan reviewing the ’809 Application would understand which formula for AIBW to use. Plaintiff is incorrect. The undisputed, intrinsic evidence demonstrates that the term AIBW, which forms the basis for each of plaintiff's three independent claims, is indefinite. Plaintiff attempts to create a factual dispute by relying on the disagreements between defendant's expert and plaintiff's experts on whether a skilled artisan would understand the scope of the claims in the ’809 Application with reasonable certainty. But plaintiff's reliance on this extrinsic evidence is unavailing where, as here, the ’809 Application and the intrinsic evidence make clear that the claims in the ’809 Application are indefinite. See Berkheimer , 881 F.3d at 1363 ("We look first to the language of the claim to determine whether the meaning of [the term] is reasonably clear."). The Federal Circuit has also cautioned that a party "cannot transform legal analysis about the meaning or significance of the intrinsic evidence into a factual question simply by having an expert testify on it." Teva , 789 F.3d at 1342. In accordance with Teva therefore, plaintiff cannot transform the meaning or significance of the intrinsic evidence relevant to the ’809 Application by relying on extrinsic evidence in the form of expert reports. Accordingly, there is no factual dispute that precludes a finding of indefiniteness with respect to the ’809 Application.
Seeking to avoid the consequences of Teva , plaintiff cites to Nevro Corp. v. Boston Scientific Corp. , 955 F.3d 35 (Fed. Cir. 2020) for the proposition that the ultimate determination of indefiniteness may rest on necessary subsidiary fact findings. But Nevro does not hold that questions of indefiniteness always rest on factual findings and the resolution of factual disputes. In Nevro , the district court entered summary judgment finding that some patent claims were invalid as indefinite. Indeed, in Nevro , the Federal Circuit did not require that any questions of indefiniteness be resolved at trial; instead, where the Federal Circuit held that the district court erred on the question of whether a term was indefinite, the Federal Circuit provided its own construction of the disputed term.
* * *
In sum, the ‘809 Application lacks the requisite specificity in defining IBW and AIBW and fails to provide a skilled artisan with reasonable certainty as to the scope of the claims covered by the ‘809 Application. Accordingly, defendant's motion for summary judgment in this regard must be granted.
IV.
Defendant next argues that the claims of the ‘809 Application are obvious and thus unpatentable. In support of its obviousness argument, defendant asserts: (i) that the prior art taught using IMGN853 to treat peritoneal and ovarian cancers ; (ii) that the prior art disclosed dosing at around 6mg/kg of total body weight and that, for most of the population, this is the same as dosing at 6mg/kg of AIBW; (iii) that dosing by AIBW was a known method for dosing drugs that treat cancer ; (iv) that routine optimization of dosing practices would have reached the 6mg/kg of AIBW method sought to be patented in the ‘809 Application; and (v) that the secondary considerations asserted by plaintiff are not probative. By contrast, plaintiff asserts: (i) that without the benefit of confidential data and analysis 6mg/kg of AIBW dosing is not obvious; (ii) that a skilled artisan would not have looked to AIBW dosing to solve problems of ocular toxicity that may result from use of IMGN853; (iii) that, when switching to AIBW dosing resulted in the elimination of higher ocular events, it was an unexpected result; (iv) that IMGN853 is a promising treatment for cancer and satisfied a long-felt need among patients; and (v) that at least one other company copied plaintiff's use of AIBW dosing for a ovarian cancer treatment. For the reasons that follow, plaintiff's argument fails and the prior art makes 6mg/kg of AIBW dosing obvious such that the ‘809 Application is not patentable.
The Patent Act provides that an applicant cannot receive a patent if "the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious." 550 U.S. § 103. In Graham v. John Deere Co. of Kansas City , 383 U.S. 1, 86 S.Ct. 684, 15 L.Ed.2d 545 (1966), the Supreme Court set out the framework for analyzing the issue of obviousness under § 103. Under the Graham framework, "the scope of and content of the prior art are to be determined; differences between the prior art and the claims at issue are to be ascertained; and the level of ordinary skill in the pertinent art resolved." Id. at 17-18, 86 S.Ct. 684. Where there are no genuine issues of material fact with respect to this framework, a district court must determine whether the claimed invention would have been obvious to a person of ordinary skill in the art. In determining whether a claimed invention would have been obvious, Graham directs courts to analyze various secondary considerations such as "commercial success, long felt but unresolved needs, failures of others, etc." Id.
In KSR International Co. v. Teleflex, Inc. , 550 U.S. 398, 127 S.Ct. 1727, 167 L.Ed.2d 705 (2007), the Supreme Court reaffirmed this "functional approach" to questions of obviousness. Id. at 415, 127 S.Ct. 1727. The Supreme Court further emphasized that the purpose of declining to issue patents that are obvious is that a "patent for a combination which only unites old elements with no change in their respective functions ... withdraws what is already known into the field of its monopoly and diminishes the resources available to skillful men." Id. at 416, 127 S.Ct. 1727 (quoting Great Atl. & Pac. Tea Co. v. Supermarket Equip. Corp. , 340 U.S. 147, 152-53, 71 S.Ct. 127, 95 L.Ed. 162 (1950) ). Ultimately, the Supreme Court, in KSR , recognized that "[w]hen there is a design need or market pressure to solve a problem and there are a finite number of identified, predictable solutions, a person of ordinary skill has good reason to pursue the known options within his or her technical grasp." Id. at 421, 127 S.Ct. 1727.
A.
As initial matter, it is necessary to determine whether a district court can reach whether the claims within a patent application are obvious after determining that the same claims are indefinite. Simply put, the answer is yes. The Federal Circuit has recognized that "[t]he questions [of obviousness and indefiniteness] are different" and the finding that a claim is indefinite does not "imply that it is incapable of being compared to prior art to determine if one of its alternatives is anticipated or would have been obvious on the grounds asserted." Cochlear Bone Anchored Sols. AB v. Oticon Med. AB , 958 F.3d 1348, 1360 (Fed. Cir. 2020). Here, the nature of the indefiniteness of the ‘809 Application does not preclude a comparison of the ‘809 Application to the prior art, as each of the independent claims relies on dosing IMGN853 at 6mg/kg of AIBW without regard for the specific AIBW formula at issue. If it is necessary to narrow the dosing method to a specific AIBW formula for purposes of the obviousness analysis, then plaintiff may be taken at its word that the formula plaintiff intended to patent is the one in Example 4 of the'809 Application. Even though examples may not be used to limit the scope of the'809 Application, it is appropriate to accept that the formula provided in Example 4 is the formula for purposes of assessing obviousness. See Cochlear , 958 F.3d at 1360 (holding that a court may focus on one of an application's alternatives to determine obviousness). Accordingly, it is appropriate to consider whether the independent claims recited in the ‘809 Application are obvious.
B.
Next, it is appropriate to identify the characteristics of the person of ordinary skill in the art in this context. See Graham , 383 U.S. at 17-18, 86 S.Ct. 684. Plaintiff's experts, Drs. Shah and Tolcher, both assert that a person of skill in the art of immunology, cancer treatment, and immunoconjugates would "typically have an M.D. degree or Ph.D. degree in Pharmacology or a Biology-related field and experience working with immunoconjugates." Exh. 47-3 ("Dr. Shah Opening Report"); Exh. 47-4 ("Dr. Tolcher Opening Report"). Defendant's expert, Dr. Figg, asserts that a person of ordinary skill in the art "would have an advanced degree in clinical pharmacy or clinical pharmacology and at least two years of experience in the field of clinical pharmacy, clinical pharmacology, or drug development with an emphasis on oncology agents or would be a clinical oncologist with expertise in drug development and similar years of experience." Exh. 55-3 ("Dr. Figg Opening Report"). Thus, the parties' three experts in this case appear to have essentially similar definitions of a person of ordinary skill in the art. Indeed, all three agree that their opinions would be unaffected if the other party's view of a person of ordinary skill in the art were to be adopted. Thus, for purposes of this Memorandum Opinion, a person of ordinary skill in the art is an individual with an advanced degree in pharmacology with experience in drug development, immunoconjugates, or oncology.
See Dr. Shah Opening Report ¶ 30 ("My opinion does not change under Defendant's definition of a POSA."); Dr. Tolcher Opening Report ¶ 56 ("My opinion does not change under Defendant's definition of a POSA."); Dr. Figg Opening Report ¶ 23 ("The opinions expressed herein would not change if I adopted [plaintiffs] definition of a POSA.").
C.
To determine whether a patent application is invalid for obviousness, Graham next teaches that a district court must determine what the prior art teaches and how that prior art compares to the invention claimed in the patent application at issue. And significantly, the Supreme Court, in KSR , makes clear that where "the content of the prior art, the scope of the patent claim, and the level of ordinary skill in the art are not in material dispute, and the obviousness of the claim is apparent in light of these factors, summary judgment is appropriate." KSR , 550 U.S. at 427, 127 S.Ct. 1727. Importantly, the KSR decision also clarified the role of experts in determining obviousness. Indeed, the Supreme Court noted that, to the extent the Federal Circuit "understood the Graham approach to exclude the possibility of summary judgment when an expert provides a conclusory affidavit addressing the question of obviousness, it misunderstood the role expert testimony plays in the analysis." Id. at 426, 127 S.Ct. 1727. In this regard, the Supreme Court, in KSR , further made clear that the "ultimate judgment of obviousness is a legal determination" and that conflicting expert declarations on that ultimate question do not preclude summary judgment. Id. at 427, 127 S.Ct. 1727. Indeed, in the wake of the KSR decision, the Federal Circuit has endorsed "common sense" reasoning with respect to obviousness. Perfect Web Techs., Inc. v. InfoUSA, Inc. , 587 F.3d 1324, 1330 (Fed. Cir. 2009). Other Federal Circuit opinions have also emphasized that where the only disagreement between the parties is whether there was a motivation to combine the prior art that existed, summary judgment is appropriate. Here, the record makes clear the nature of the prior art that existed and that there are no factual inquiries in dispute; the parties only dispute inferences to be drawn from the undisputed facts.
See Wyers v. Master Lock Co. , 616 F.3d 1231, 1240 (Fed. Cir. 2010) (citing Perfect Web , 587 F.3d at 1330 ; Ball Aerosol & Specialty Container, Inc. v. Limited Brands, Inc. , 555 F.3d 984 (Fed. Cir. 2009) ; Sundance Inc. v. DeMonte Fabricating, Ltd. , 550 F.3d 1356 (Fed. Cir. 2008) ).
As previously discussed in Section IV.A, there is no dispute concerning the scope of the ‘809 Application if, as appropriate, the dosing formula stated in Example 4 is accepted for purposes of the obviousness analysis. Similarly, as discussed in Section IV.B there is no dispute as to the level of skill of the person of ordinary skill in the art. A review of the record further supports that there are no disputes that the prior art taught the following concepts relevant to the ‘809 Application:
• The immunoconjugate recited in the ‘809 Application, IMGN853, was known in the art and was already used to ovarian and peritoneal cancers. That immunoconjugate has also been previously described in Ab ‘528, Carrigan ‘675, Ab '181, and Lutz ‘282.
• The prior art teaches that "optimum dosing," "dosing methodologies," and "repetition rates" for IMGN853 can "easily" be determined.
• The prior art also teaches dosing of IMGN853 in terms of milligrams per kilogram of total body weight. In Lutz ‘282, the focus was specifically on dosing around 6mg/kg of total body weight.
• Dosing based on IBW or AIBW was also known in the art prior to October 8, 2013. Several articles had noted that failure to adjust doses could lead to possible negative outcomes, because, as one article suggested, dosing based on AIBW helps normalize the volume of drug distribution. At least two articles (Geraghty and Fuchs) recommended dosing drugs based on the lower of AIBW or actual body weight.
See supra Section I, facts 18 and 19.
See supra Section I, facts 22, 23, and 27.
See supra Section I, facts 30 and 31.
See supra Section I, fact 33.
Thus, this case, as the Supreme Court discussed in KSR , is one in which summary judgment may be appropriate, if the obviousness of the ‘809 Application is apparent on the undisputed summary judgment record. A review of the record confirms that the ‘809 Application is obvious when the prior art's teachings are taken into account.
The ‘809 Application claims to add to the prior art dosing of IMGN853 at 6mg/kg of AIBW to treat ovarian and peritoneal cancers in order to avoid certain toxic ocular events. Stated succinctly, each of the elements of the ‘809 Application's claims is covered by the prior art: (i) IMGN853 was known to treat ovarian and peritoneal cancers ; (ii) dosing of IMGN853 of around 6mg/kg of total body weight was disclosed by the prior art; and (iii) AIBW was a known method of avoiding negative outcomes associated with dosing by other weight measures. It is thus clear from the record that the prior art teaches every individual element of the asserted claims of the ‘809 Application; only their combination is not in the prior art. See Pregis Corp. v. Kappos , 700 F.3d 1348, 1354 (Fed. Cir. 2012) (upholding finding of obviousness where the prior art taught every element of the asserted claims).
See supra Section I, facts 30 and 31 (discussing Lutz ‘282).
Indeed, the record reflects that the shift from 6mg/kg of total body weight dosing to 6mg/kg of AIBW dosing does not significantly change the dose for patients who are not significantly overweight or underweight. See Dr. Shah Depo. Tr. at 75:16-81:3; Exh. 24 (referenced chart). Defendant's expert, Dr. Figg, explained this point, stating "[t]he closer the person's actual body weight is to their ideal body weight, the less significant AIBW dosing becomes – and the trouble of calculating AIBW is not worth the effort." Dr. Figg Opening Report ¶ 99. Indeed, Drs. Shah and Tolcher agree that use of AIBW was developed for dosing in patients who were far from their ideal body weight, namely patients who were obese. See Dr. Shah Opening Report ¶ 57; Dr. Tolcher Opening Report ¶ 207. Thus, for many patients, dosing by total body weight and dosing by AIBW would not result in significant differences in the doses of IMGN853 prescribed for that patient and therefore the ‘809 Application would cover the dosages taught by Lutz ’282. Thus, the ’809 Application would "effectively remove from the public that which is in the public domain by virtue of its inclusion in, or obviousness from, the prior art." In re Huai-Hung Kao , 639 F.3d 1057, 1073 (Fed. Cir. 2011).
Indeed, "where there is a range disclosed in the prior art," as in Lutz ’282, and "the claimed invention falls within that range," there is a "presumption of obviousness." Tyco Healthcare Grp. LP v. Mutual Pharm. Co., Inc. , 642 F.3d 1370, 1372 (Fed. Cir. 2011). Here, the dosage amount (6mg/kg) claimed by the ’809 Application falls within the range disclosed by Lutz ’282, but the specific dosing methodology used (total body weight v. AIBW) differs. Although a presumption of obviousness may not apply directly in this case, the Tyco language is still instructive as to what should be considered obvious for patents covering dosing.
In Huai-Hung Kao , the Federal Circuit addressed the obviousness of three patent applications relating to drug formulations containing opioids. In particular, the novel invention claimed by one patent was " ‘providing information’ about a previously undiscovered correlation between renal failure and bioavailability." 639 F.3d at 1073. The Federal Circuit recognized that the "correlation between the renal impairment and bioavailability was not known," but nonetheless held that the patent application failed as obvious because "the administration of controlled release oxymorphone is squarely present in the prior art." Id. Similarly, here, although the specific correlation between AIBW dosing and a reduction in the ocular toxicity of IMGN853 was not known, AIBW dosing was squarely present in the prior art and a known means of reducing negative outcomes for drug administration.
Seeking to avoid this result, plaintiff argues that a person of ordinary skill in the art would not have been motivated to look to AIBW dosing as a means of reducing ocular toxicity because that person would not have known that IMGN853 could result in ocular toxicity at certain dosages. The record, however, reflects otherwise. First, as plaintiff's expert notes, ocular toxicity was a known negative effect of antibody-drug-conjugates or ADCs, like IMGN853. Thus, a person of ordinary skill in the art would have known that there were a limited number of dosing methodologies to solve ocular toxicity issues and, based on the history of ocular toxicity problems for ADCs, would have been motivated to investigate such options. Second, as Dr. Tolcher conceded in his deposition, IMGN853 could not have been brought to market without human testing. Specifically, in Phase 1 of human testing, the studies are designed "to determine the metabolism and pharmacologic actions of drugs in humans, the side effects associated with increasing doses, and, if possible, to gain early evidence on effectiveness." 21 C.F.R. § 312.21. Thus, the ocular toxicity of IMGN853 specifically would have been known as a result of human testing. Third, AIBW dosing was a common dosing methodology. Fourth, AIBW dosing was known in the prior art to normalize volume of distribution and to reduce negative outcomes in drug administration.
See Dr. Tolcher Opening Report ¶ 155 ("Off-target ocular toxicity – especially for DM4 and MMAF payloads – has always been a challenge in designing and manufacturing ADCs.").
See Dr. Tolcher Depo. Tr. at 24:6-8; 21 C.F.R. § 312.21 (describing the phases of testing for new drugs, including human testing).
See A3999-40002; Exh. 25 at 60; Dr. Shah Depo. Tr. at 40:7-12; Dr. Tolcher Depo. Tr. at 55:3-13.
See A3998-40002; see also Exhs. 7 and 8. Moreover, as plaintiff's expert concedes in his report AIBW dosing has been used to account for both volume normalization and altered drug distribution. See Dr. Shah Opening Report ¶¶ 58, 208.
Together, these facts point persuasively to the fact that a person of ordinary skill in the art would have been motivated to investigate AIBW dosing to avoid ocular toxicity and would have been motivated to combine the prior art's teachings to reach a dosage of 6mg/kg of AIBW. As the Federal Circuit has noted, where "the experimentation needed to arrive at the claimed dosages was nothing more than routine," a patent is invalid for obviousness. Merck & Co., Inc. v. Biocraft Labs., Inc. , 874 F.2d 804, 809 (Fed. Cir. 1989). In Merck , the patent claimed the dosing of two drugs, which were diuretics, to avoid sodium excretion and the testing performed by Merck to reach those dosages were those that "all pharmaceutical companies[follow]." Id. The Federal Circuit therefore held that the recited claims were obvious because they were "[r]eached by means of routine procedures, and produc[ed] only predictable results." Id. Similarly, in the circumstances presented, a person of ordinary skill of the art would expect IMGN853 to cause ocular toxicity, would find that it did cause ocular toxicity through routine and legally required studies, and would have been motivated to try dosing by AIBW in order to reduce ocular toxicity events.
This conclusion finds firm support in the Federal Circuit's decision in Boehringer Ingelheim Pharms. Inc. v. Mylan Pharms., Inc. , 803 F. App'x 397 (Fed. Cir. 2020). There, the Federal Circuit affirmed a finding of obviousness of a dosing methodology where the district court determined that a person skilled in the art would have a reasonable expectation of arriving at the claimed dosages "through routine experimentation." Id. at 402.
Next, plaintiff argues that, without that data, a person of ordinary skill in the art would not know whether AIBW dosing would be effective in reducing ocular toxicity. In support, plaintiff cites Personal Web Technologies, LLC v. Apple, Inc. , 848 F.3d 987 (Fed. Cir. 2017), for the proposition that the law requires a "clear, evidence-supported account of the contemplated workings of the combination [which] is a prerequisite to adequately [sic] explaining and supporting a conclusion" of obviousness. Id. at 994. This argument fails because plaintiff misreads Personal Web. In Personal Web , the basis for the Federal Circuit's decision was that the PTAB failed to discuss "how the combination" of the two pieces of prior art "was supposed to work." Id. (emphasis added). Moreover, the quote from Personal Web upon which plaintiff contains an important qualifier, omitted by plaintiff, where the Federal Circuit indicates that this point is relevant "at least in this case. " Id. (emphasis added). Here, it is clear how the combination of the prior art is supposed to work and that a person of ordinary skill in the art would be motivated to combine the teachings of the prior art given the known ocular toxicity issues with ADCs, like IMGN853, and the limited dosing methodologies available. Moreover, it is important to note, that in Carrigan ’675, an application owned by plaintiff, it is recognized that dosing of IMGN853 could "easily" be determined. A220-221. Additionally, plaintiff appears to rely on Personal Web to require that a person of ordinary skill in the art must know with certainty that an obvious combination would be successful. The law does not require as much. As defendant correctly points out, the law does not require "absolute predictability of success." In re O'Farrell , 853 F.2d 894, 903 (Fed. Cir. 1988) (finding patent obvious where the prior art provided a "reasonable expectation of success"). Indeed, the Federal Circuit has explicitly rejected plaintiff's argument that certainty of success is required, when it noted in Pfizer, Inc. v. Apotex, Inc. , 480 F.3d 1348 (Fed. Cir. 2007) that "obviousness cannot be avoided simply by a showing of some degree of unpredictability so long as there was a reasonable probability of success." Id. at 1364. Here, there was a reasonable probability of success in reducing ocular toxicity by exploring dosing IMGN853 by AIBW, at the dosages disclosed by Lutz ’282, and a person skilled in the art would be motivated to combine the prior art in such a manner.
See KSR , 550 U.S. at 421, 127 S.Ct. 1727 (recognizing that an invention may be obvious when there is a design need and "a finite number of identified, predictable solutions").
Plaintiff notes that the sentence immediately preceding the language indicating that dosing could easily be determined provides that: "Optimal dosing schedules can be calculated from measurements of drug accumulation in the body of the patient and will vary depending on the relative potency of an individual antibody or agent." A3224, at ¶ 237. Plaintiff apparently relies on this line to point out that the prior art does not specify what the ultimate dosing should be or whether it would be safe. Plaintiff's reliance on this line is insufficient to undermine the position that a person of ordinary skill in the art would have been motivated to combine the teachings of the prior art and that such person would have a reasonable probability of success in reaching the correct dosage. In this regard, it is not necessary for the prior art to cover a claimed invention so explicitly. But the specific language in the prior art that dosing can be "easily" determined, lends support to the position that a person skilled in the art would have been motivated to combine the teachings of the prior art and that such person would have a reasonable probability of success in reaching the correct dosage.
Plaintiff also argues that secondary considerations of obviousness weigh in favor of non-obviousness. This argument is mistaken. To accord substantial weight to secondary considerations, "the evidence of secondary considerations must have a ‘nexus’ to the claims," Henny Penny Corp. v. Frymaster, LLC , 938 F.3d 1324, 1332 (Fed. Cir. 2019), and "[t]he patentee bears the burden of showing that a nexus exists," WMS Gaming Inc. v. Int'l Game Tech. , 184 F.3d 1339, 1359 (Fed. Cir. 1999). Plaintiff's arguments on secondary considerations fail in both respects. Plaintiff first argues that the AIBW dosing caused unexpected results by "eliminating" Grade 3 or higher ocular toxicity events. Opp'n at 27. To begin with, plaintiff overstates the effects of AIBW dosing, as plaintiff's expert witness noted that in the Phase 3 human studies ocular toxicity events still occurred with AIBW dosing and one to two percent of patients experienced Grade 3 or 4 ocular events. See Exh. 18, Dr. Tolcher Reply Report at ¶ 77. More importantly, to show that the results of AIBW dosing were unexpected, plaintiff must compare those results to the ocular toxicity of other means of dosing IMGN853, such as total body weight dosing. Plaintiff does so but relies on a 10-person study of persons who received 5mg/kg of total body weight, in which one person showed a Grade 3 ocular event. See Dr. Tolcher Opening Report at ¶ 179. Plaintiff's reliance on this meager study is misplaced. As Dr. Tolcher recognized, in his deposition, the Phase III results of AIBW dosing could not properly be compared to the 10-person total body weight dosing study. Specifically, as Dr. Tolcher put it "you're asking me to compare apples to oranges," because one was a very large study and the other was a limited sample size. See Dr. Tolcher Depo. Tr. at 169:13-20. Dr. Tolcher further explained that "no biostatistician is going to compare a small sample size that is part of the hypothesis generating in early studies and try to compare it to a larger study based on a phase 3 study." Id. at 171:7-12. Moreover, in the Phase 3 AIBW dosing study, other prophylactic eye care in the form of corticosteroids and lubricating eye drops were used to treat patients. See Dr. Figg Opening Report ¶¶ 105-107; Dr. Tolcher Opening Report ¶¶ 46, 172, 175. Thus, plaintiff's argument that the results of the AIBW dosing study were unexpected fails to demonstrate that AIBW and total body weight dosing result in different levels of ocular toxicity. Moreover, the use of other prophylactic measures in the Phase III study clouds the nexus between the use of AIBW dosing and the reduction in adverse ocular events such that the results cannot be unexpected. In sum, plaintiff fails to demonstrate a nexus between AIBW dosing and ocular toxicity levels when compared to total body weight dosing and, even if such reduction occurred in Phase 3 studies, fails to demonstrate that any such reduction in ocular events is due to AIBW dosing. Accordingly, plaintiff cannot persuasively argue that the results of AIBW dosing led to unexpected results.
To establish that AIBW dosing eliminates ocular toxicity for IMGN853, plaintiff relies on earlier Phase I human studies, but the Phase I study was based on a limited sample size and elimination of ocular toxicity events was not borne out by the larger Phase III study, which showed that one to two percent of patients experienced Grade 3 or higher events.
Importantly, in an article published in 2018, researchers (including researchers from plaintiff) recognized: first, that "[i]t is well established that the eye is susceptible to toxic insults" in response to treatment and, second, that "[p]rimary prophylactic use of topical corticosteroid eye drops resulted in a trend toward symptomatic improvement and a reduction in ocular [adverse event]-related dose modifications in patients treated with [IMGN853]." Exh. 39.
See Bristol-Myers Squibb Co. v. Teva Pharms. USA, Inc. , 752 F.3d 967, 977 (Fed. Cir. 2014) ("To be particularly probative, evidence of unexpected results must establish that there is a difference between the results obtained and those of the closet prior art, and that the difference would not have been expected by one of ordinary skill in the art at the time of the inventions.").
See ArcelorMittal France v. AK Steel Corp. , 700 F.3d 1314, 1326 (Fed. Cir. 2012) (finding no nexus where the alleged superior result was due to unclaimed features).
Plaintiff next claims that IMGN853 has received industry praise. To begin with, there is no nexus to the claimed invention in the ’809 Application, 6 mg/kg of AIBW dosing of IMGN853. Plaintiff primarily relies on statements by Drs. Kathleen Moore and Michael Birrer. See Dr. Tolcher Opening Report at ¶¶ 234, 236-38. Defendant also notes that Drs. Moore and Birrer are Immunogen researchers praising their own work. Plaintiff does not dispute this but argues that this does not undermine the force of their praise. See Opp'n at 28. The Federal Circuit has held otherwise. See In re Cree, Inc. , 818 F.3d 694 (Fed. Cir. 2016) (holding that "self-serving statements from researchers about their own work do not have the same reliability"). Although, at this juncture, it is unnecessary to make any determinations about the reliability of statements by Drs. Moore and Birrer, the fact that they are Immunogen researchers praising their own work lessens the force of their praise and certainly does not constitute industry praise. Plaintiff also relies on statements from Dr. Figg, defendant's expert, at his deposition and an article. None of the statements on which plaintiff relies, however, demonstrates industry praise for the claimed IMGN853 dosage of 6mg/kg of AIBW in the ’809 Application; rather, Dr. Figg praises IMGN853 as a drug and either does not discuss dosing or admits only that dosing "maybe" reduced ocular toxicity. Once again, plaintiff's arguments in this regard are unpersuasive; they lend minimal support, if any, to a conclusion of non-obviousness. See Bos. Sci. SciMed, Inc. v. Iancu , 811 F. App'x 618, 628 (Fed. Cir. 2020).
See Dr. Figg Depo. Tr. at 17:17-18:6 (agreeing that IMGN853 itself is a promising drug); id. at 19:3-6 (praising IMGN853 itself, not the AIBW dosing regimen); id. at 182:14-22 (admitting only that the dosing regimen "maybe" reduced ocular toxicity); id. at 192:14-18 (agreeing that IMGN853 itself demonstrates a favorable risk profile); Exh. 54 (praising IMGN853 without discussing dosing).
Plaintiff also argues that AIBW dosing satisfies a long-felt need for an effective and well-tolerated treatment for ovarian and peritoneal cancers. As defendant correctly notes, however, a distinction must be drawn between a long-felt need for IMGN853 and a long-felt need for a dosing regimen for IMGN853. The Federal Circuit recognizes, "whether there is long-felt need is analyzed as of the date of an articulated identified problem and evidence of efforts to solve that problem." Texas Instruments, Inc. v. U.S. Int'l Trade Comm'n , 988 F.2d 1165, 1178 (Fed. Cir. 1993). Here, IMGN853 was only developed in 2011 and Phase I testing did not begin until 2012. Plaintiff then sought to patent 6mg/kg of AIBW of IMGN853 dosing in 2013. When the period between the development of IMGN853 and the development of 6mg/kg of AIBW dosing is examined, it is relatively short. In Pentec, Inc. v. Graphic Controls Corp. , 776 F.2d 309 (Fed. Cir. 1985), the Federal Circuit addressed both of these issues, noting that the patentee's testimony indicated "the need for disposable pens per se , not for the claimed invention." Id. at 316. Similarly, here, Plaintiff's experts fail to establish the required nexus between the claimed dosing regimen and any long-felt need. Rather, plaintiff focused on the long-felt need for an efficacious cancer drug – which was satisfied by the development of IMGN853 an invention not claimed in the ’809 Application. Additionally, in Pentec , the Federal Circuit noted that, "[i]n light of the short period between the introduction of disposable pens and the time the invention was made, the district court's findings that GC failed to prove the existence of a long[-]felt need was not clearly erroneous." Id. Indeed, the record here conclusively points to the fact that AIBW dosing of IMGN853 was simply the use of a known dosing method with a newly developed drug. Thus, there is no persuasive evidence of, nor is there any factual dispute, that there was not a long-felt need for a dosing regimen for IMGN853.
Moreover, other than Lutz ‘282, there is no evidence in the record about other persons efforts to attempt to determine the appropriate dosing of IMGN853.
See Jore Corp. v. Kouvato, Inc. , 117 F. App'x 761, 765 (Fed. Cir. 2005) ("If the fact of a new design in an old art field demonstrated a long-felt need for the new design, long-felt need would not be a meaningful indicator of nonobviousness but would merely be another way of saying that a particular design is novel.").
Finally, plaintiff claims that another ADC developer, Sutro Biopharma, Inc. ("Sutro"), has copied plaintiff's work by using AIBW dosing for Sutro's own drug for treating ovarian cancer. But, to be probative on obviousness, "more than the mere fact of copying is necessary." Sealy Tech., LLC v. SSB Mfg. Co. , 825 F. App'x 801, 807 (Fed. Cir. 2020). In this respect, plaintiff relies on Dr. Tolcher's expert report, which states that Sutro, after becoming aware of plaintiff's success with dosing IMGN853 by AIBW, commenced a clinical trial for an ADC where subjects will be dosed based on AIBW. See Dr. Tolcher Opening Report ¶¶ 247-252. The evidence of copying is thus that Sutro is using AIBW dosing for an ADC to treat ovarian cancer. See Opp'n at 30 (arguing that "Sutro duplicated a particularly relevant feature: AIBW dosing"). But, the invention at issue here is the specific 6mg/kg of AIBW dosing set forth in Example 4 of the ’809 Application. As discussed supra , AIBW dosing was a known method of dosing and a known means of reducing negative outcomes of drug treatments. By arguing that all that is necessary to constitute copying is the use of AIBW dosing for an ADC, plaintiff improperly seeks to expand the scope of the ’809 Application to cover AIBW dosing for any ADC. See Liqwd, Inc. v. L'Oreal USA, Inc. , 941 F.3d 1133, 1137 (Fed. Cir. 2019) (citing Iron Grip Barbell Co. v. USA Sports, Inc. , 392 F.3d 1317, 1325 (Fed. Cir. 2004) ) (noting that "copying requires the replication of a specific product"). Moreover, as Dr. Tolcher testified in his deposition, the dosing of one ADC "tells you nothing" about the dosing of another ADC, "because the toxicides of an ADC are very specific for each individual drug." Dr. Tolcher Depo. Tr. at 27:21-28:22. Here, plaintiff and Sutro are dosing different drugs, plaintiff is dosing IMGN853 whereas Sutro is dosing its own ADC cancer drug, and there is no evidence in record regarding any efforts by Sutro to develop a dosing regimen for its ADC drug. See Pentec , 776 F.2d at 317 (copying argument should be given "little weight" where the alleged copier's "effort to develop their own solution was not shown to have been extensive" and where the "product is not identical to the claimed invention"). Accordingly, plaintiff's copying argument is unpersuasive and does not support a conclusion of non-obviousness.
See also In re GPAC , 57 F.3d 1573, 1580 (Fed. Cir. 1995) ("[M]ore than the mere fact of copying by an accused infringer is needed to make that action significant to a determination of the obviousness issue.").
In his Reply Report, Dr. Tolcher notes that Sutro is beginning clinical trials and that, at least one such trial, will use 6mg/kg dosing. This does not alter the analysis or conclusion reached here, because (i) Sutro is not dosing IMGN853, which is what is claimed by the ’809 Application; (ii) Sutro "had yet to determine the maximum tolerated dose of Sutro's tested ADC," Dr. Tolcher Reply Report 85, and, therefore, is not committed to the 6mg/kg AIBW dosing claimed by the ’809 Application; (iii) there is no evidence of Sutro's efforts to solve a problem of ocular toxicity prior to beginning the studies that are alleged to constitute copying; and (iv) as Dr. Tolcher testified, the dosing of one ADC "tells you nothing" about how to dose another ADC, Dr. Tolcher Depo. Tr. at 27:21-28:22. Thus, even if Sutro uses 6mg/kg of AIBW dosing of its own ADC, plaintiff cannot establish that Sutro is replicating plaintiff's "specific product" or that Sutro went to extensive efforts to "develop their own solution" as required by Federal Circuit precedent. Liqwd, Inc. , 941 F.3d at 1137 ; Pentec , 776 F.2d at 317.
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In sum, the ‘809 Application is both fatally indefinite and fatally obvious. The ’809 Application fails to define IBW or AIBW in a manner that would provide person of ordinary skill in the art with reasonable certainty as to the scope of the claimed invention, because those terms are only defined in terms of "examples" in the ’809 Application. Moreover, the ’809 Application is unpatentable because it is an obvious combination of the teachings of the prior art. AIBW dosing existed prior to 2013 and Lutz ’282 taught that IMGN853 should be dosed at around 6mg/kg of total body weight. In light of the ocular toxicity problems that arose as part of required human testing of IMGN853, it would have been obvious to a person of ordinary skill in the art to try AIBW dosing in line with the amounts taught by Lutz ’282, which is what the ‘809 Application seeks to patent. Plaintiff's arguments regarding secondary considerations of obviousness are not persuasive and do not establish a conclusion of non-obviousness nor do they present any genuine issue of material fact as to obviousness.
Because the ‘809 Application fails as being both fatally indefinite and fatally obvious, it is unnecessary to reach or decide defendant's obviousness-type double patenting arguments. Accordingly, defendant's motion for summary judgment must be granted on the issues of indefiniteness and obviousness.
An appropriate Order will issue.