Amgen Inc. v. Sandoz Inc.

          ORDER CONSTRUING CLAIMS

          RICHARD SEEBORG United States District Judge

         I. INTRODUCTION

         Amgen, Inc. and Sandoz Inc., Sandoz International GmbH, and Sandoz GmbH (collectively “Sandoz”) compete to develop, manufacture, promote, and sell biopharmaceutical products, including those used to facilitate stem-cell transplantation. Amgen holds two patents at issue in this action: U.S. Patent Nos. 6, 162, 427 (“the ’427 Patent”) and 8, 940, 878 (“the ’878 Patent”). Amgen accuses Sandoz of infringing those patents. The parties seek construction of ten terms pursuant to Markman v. Westview Instruments, Inc., 52 F.3d 967 (Fed. Cir. 1995) (en banc). For the reasons set forth below, the disputed terms are construed as follows.

         II. BACKGROUND

         In 2014, Amgen filed claims against Sandoz for infringement of the ’427 patent, “Combination of G-CSF with a Chemotherapeutic Agent for Stem Cell Mobilization.” Amgen objects to Sandoz’s efforts to market and sell ZARXIO®, a drug Amgen contends is biosimilar to its drug, NEUPOGEN®, which is commonly used to “treat[] the side effects of certain forms of cancer therapy.” FAC ¶ 11. The active ingredient in both products is filgrastim, a synthetic version of human granulocyte colony stimulating factor (“G-CSF”). Amgen also accuses Sandoz of violating California’s unfair competition law (“UCL”). In response, Sandoz asserts numerous counterclaims for declaratory judgments of compliance with the Biosimilars Price Competition and Innovation Act (“BPCIA”), non-infringement, and patent invalidity. In March 2015, Sandoz obtained partial judgment in its favor with respect to the UCL claim and Sandoz’s claim for a declaratory judgment of compliance with the BPCIA pursuant to Federal Rule of Civil Procedure 54(b). The parties jointly requested to stay these proceedings until the issuance of the Federal Circuit’s mandate. Dkt. No. 111 at 3.

         Amgen then appealed to the Federal Circuit. During the pendency of the appeal, the Federal Circuit entered an injunction to prevent Sandoz from marketing, selling, or importing ZARXIO®. The Federal Circuit affirmed dismissal of the UCL claim, and affirmed in part and reversed in part the order regarding the BPCIA. See Amgen Inc. v. Sandoz Inc., 794 F.3d 1347 (Fed. Cir. 2015). Sandoz filed a petition for en banc review, which is still pending in the Federal Circuit.

         Following the issuance of the Federal Circuit’s mandate, the parties agreed to lift the stay, and Amgen filed a First Amended Complaint, asserting one additional claim of patent infringement. Amgen now contends Sandoz employs a method of protein capture that infringes the ’878 patent, entitled “Capture Purification Processes for Proteins Expressed in a Non-Mammalian System.”

         III. LEGAL STANDARD

         Claim construction is a question of law to be determined by the court. Markman, 52 F.3d at 979. “Ultimately, the interpretation to be given a term can only be determined and confirmed with a full understanding of what the inventors actually invented and intended to envelop with the claim.” Renishaw PLC v. Marposs Societa’ per Azioni, 158 F.3d 1243, 1250 (Fed. Cir. 1998). Accordingly, a claim should be construed in a manner that “most naturally aligns with the patent’s description of the invention.”

         The first step in claim construction is to look to the language of the claims themselves. “It is a ‘bedrock principle’ of patent law that ‘the claims of a patent define the invention to which the patentee is entitled the right to exclude.’” Phillips v. AWH Corp., 415 F.3d 1303, 1312 (Fed. Cir. 2005) (quoting Innova/Pure Water, Inc. v. Safari Water Filtration Sys., Inc., 381 F.3d 1111, 1115 (Fed. Cir. 2004)). A disputed claim term should be construed in a manner consistent with its “ordinary and customary meaning, ” which is “the meaning that the term would have to a person of ordinary skill in the art in question at the time of the invention, i.e., as of the effective filing date of the patent application.” Phillips, 415 F.3d at 1312-13. The ordinary and customary meaning of a claim term may be determined solely by viewing the term within the context of the claim’s overall language. See Id. at 1314 (“[T]he use of a term within the claim provides a firm basis for construing the term.”). Additionally, the use of the term in other claims may provide guidance regarding its proper construction. Id. (“Other claims of the patent in question, both asserted and unasserted, can also be valuable sources of enlightenment as to the meaning of a claim term.”).

         A claim should also be construed in a manner that is consistent with the patent’s specification. See Markman, 52 F.3d at 979 (“Claims must be read in view of the specification, of which they are a part.”). Typically the specification is the best guide for construing the claims. See Phillips, 415 F.3d at 1315 (“The specification is . . . the primary basis for construing the claims.”); see also Vitronics Corp. v. Conceptronic, Inc., 90 F.3d 1576, 1582 (Fed. Cir. 1996) (“[T]he specification is always highly relevant to the claim construction analysis. Usually, it is dispositive; it is the single best guide to the meaning of a disputed term.”). In limited circumstances, the specification may be used to narrow the meaning of a claim term that otherwise would appear to be susceptible to a broader reading. See SciMed Life Sys., Inc. v. Advanced Cardiovascular Sys., Inc., 242 F.3d 1337, 1341 (Fed. Cir. 2001) (“Where the specification makes clear that the invention does not include a particular feature, that feature is deemed to be outside the reach of the claims of the patent, even though the language of the claims, read without reference to the specification, might be considered broad enough to encompass the feature in question.”); Phillips, 415 F.3d at 1316 (“[T]he specification may reveal an intentional disclaimer, or disavowal, of claim scope by the inventor. In that instance as well, the inventor has dictated the correct claim scope, and the inventor’s intention, as expressed in the specification, is regarded as dispositive.”). Precedent forbids, however, a construction of claim terms that imposes limitations not found in the claims or supported by an unambiguous restriction in the specification or prosecution history. Laitram Corp. v. NEC Corp., 163 F.3d 1342, 1347 (Fed. Cir. 1998) (“[A] court may not import limitations from the written description into the claims.”); Comark Commc’ns., Inc. v. Harris Corp., 156 F.3d 1182, 1186 (Fed. Cir. 1998) (“[W]hile claims are to be interpreted in light of the specification, it does not follow that limitations from the specification may be read into the claims.” (internal quotation marks and alterations omitted)); SRI Int’l v. Matsushita Elec. Corp. of Am., 775 F.2d 1107, 1121 (Fed. Cir. 1985) (en banc) (“It is the claims that measure the invention.”) (emphasis in original). A final source of intrinsic evidence is the prosecution record and any statements made by the patentee to the United States Patent and Trademark Office (“PTO”) regarding the scope of the invention. See Markman, 52 F.3d at 980.

         Courts may also consider extrinsic evidence, such as expert testimony, dictionaries, or technical treatises, especially if such sources are “helpful in determining ‘the true meaning of language used in the patent claims.’” Phillips, 415 F.3d at 1318 (quoting Markman, 52 F.3d at 980). Ultimately, while extrinsic evidence may aid the claim construction analysis, it cannot be used to contradict the plain and ordinary meaning of a claim term as defined within the intrinsic record. See Phillips, 415 F.3d at 1322-23.

         IV. DISCUSSION

         A. The ’427 Patent

         Hematopoietic stem cells naturally occur in the human body and are capable of proliferation and differentiation into cells that comprise the blood and immune systems. In other words, they are blood-forming stem cells.^[1] These cells self-renew and reside primarily in bone marrow.

         Peripheral stem cell transplantation is a process used to replace damaged blood-forming stem cells-the sort of cellular damage chemotherapy usually causes. Peripheral blood is the blood that circulates through the body. Before peripheral stem cell transplantation can occur, the doctor must collect blood-forming stem cells for later transplantation. Collection requires “mobilizing” stem cells in the bone marrow to move into the peripheral blood stream. Once the stem cells have mobilized, doctors collect them using a process called leukapheresis, which separates the stem cells from other types of blood cells. The collected cells are then set aside for later use. The more blood-forming stem cells in the blood stream, the fewer leukapheresis sessions the patient must undergo to collect enough cells for transplantation.

         G-CSF is a protein that naturally occurs in the human body. Filgrastim is a pharmaceutical analog of human G-CSF constructed artificially in E. coli bacteria using recombinant DNA technology. Since the early 1990s, doctors and researchers have been using G-CSF in connection with chemotherapy to relieve the side effects of chemotherapy. G-CSF has also been used to facilitate mobilization of blood-forming stem cells from the bone marrow into the peripheral blood.

         After the stem-cell collection, the patient undergoes myeloablative radiation (bone marrow destruction) or myelotoxic chemotherapy (bone marrow suppression), which destroy blood-forming stem cells in the process. Once chemotherapy has been administered, the collected stem cells can be reintroduced into the bone marrow to allow for further production of new blood cells.

         Both parties agree that the ’427 patent describes a method that requires administration of G-CSF before administration of a chemotherapeutic agent. The order of administration (G-CSF first, a chemotherapeutic agent second) is the allegedly novel component of the invention. At the time of the invention, a skilled artisan knew that administration of G-CSF alone, a chemotherapeutic agent alone, or a chemotherapeutic agent followed by G-CSF could mobilize blood-forming stem cells into the blood stream. The patentees purport to have reached the revolutionary conclusion that the structured administration of G-CSF first, followed by administration of a chemotherapeutic agent was the most efficient method of stem cell mobilization. The patent claims to improve on the process of stem cell collection by following the specified order, which relieves patients of the need to attend multiple of leukapheresis sessions.

         1. “hematopoietic stem cell mobilizing-effective amount of G-CSF”

         The term “hematopoietic stem cell mobilizing-effective amount of G-CSF” appears in only claim 1, but is incorporated by reference into claims 2, 3, 4, and 6. Amgen would have the term construed to mean “an amount of G-CSF effective to mobilize hematopoietic stem cells, ” whereas Sandoz contends the term is indefinite.

         When evaluating whether a term is sufficiently definite, courts must analyze that question “from the viewpoint of a person skilled in the art at the time the patent was filed.” Nautilus, Inc. v. Biosig Instruments, Inc., 134 S.Ct. 2120, 2128 (2014) (emphasis, internal quotation marks, and alteration omitted). As noted, the claims “are to be read in light of the patent’s specification and prosecution history.” Id. When examining the definiteness of a term, courts “must take into account the inherent limitations of language, ” and therefore “[s]ome modicum of uncertainty . . . is the price of ensuring the appropriate incentives for innovation.” Id. (internal quotation marks omitted). “At the same time, a patent must be precise enough to afford clear notice of what is claimed, thereby apprising the public of what is still open to them.” Id. at 2129 (internal quotation marks omitted). “Cognizant of the competing concerns, ” the Supreme Court requires “that a patent’s claim, viewed in light of the specification and prosecution history, inform those skilled in the art about the scope of the invention with reasonable certainty.” Id.

         The first step required is to define who is a person skilled in the relevant art. This patent was written for those who practice stem-cell transplantation or study stem-cell biology. A person skilled in the relevant art is therefore one who has obtained a Ph.D. in biological sciences or an M.D. In addition, this person is one with significant experience with stem-cell biology, hematopoiesis, and stem-cell transplantation.

         Turning to the question of whether such a skilled artisan understands the phrase “hematopoietic stem cell mobilizing-effective amount of G-CSF, ” Sandoz takes aim at the word “effective” and offers three arguments for why the term is indefinite. First, it argues neither the claim language nor the specification inform skilled artisans about how many blood-producing stem cells must mobilize to be considered “effective.” In other words, a skilled artisan has no way to discern whether mobilization of one stem cell, ten stem cells, or a thousand stem cells is “effective.” Second, Sandoz insists the claim, specification, and prosecution history do not provide information for skilled artisans to tailor the procedure to the species of the patient (human, mouse, dog, horse, etc.). The final argument is that the patent does not explain how artisans should measure the level of stem-cell mobilization. At the time of the invention, practitioners knew of four methods for measuring the extent of stem cell mobilization, all of which varied considerably in terms of accuracy, consistency, and practicality. See Sandoz’s Expert Negrin Decl. ¶¶ 45-46.

         Whether adjectival limitations are indefinite depends on the context of each individual patent. In Takeda Pharm. Co. v. Mylan Inc., No. 13-CV-04001-LHK, 2014 WL 5862134, at *10-11 (N.D. Cal. Nov. 11, 2014), the district court deemed the term “effective amount” definite because the patent described the proper dose of the drug (“about 0.5 to 1, 500 mg/day”), and the claim covered treatment of a specific type of disease-reflux esophagitis. Id. at *10. In contrast, another district court concluded the term “% identity” was indefinite because “the specification identifie[d] a non-inclusive list of five methods to calculate ‘% identity’ and provide[d] that sequence alignment can be performed using any commercially available or independently developed software.” Butamax Advanced Biofuels LLC v. Gevo, Inc., 117 F.Supp.3d 632, 641 (D. Del. 2015). Similarly, in Andrulis Pharm. Corp. v. Celgene Corp., No. CV 13-1644(RGA), 2015 WL 3978578, at *3-4 (D. Del. June 26, 2015), the term “enhanced therapeutically-effective amounts of thalidomide” was held to be indefinite because “enhanced” could mean “less than additive, additive, or greater than additive.” Id. at *3.

         Here, the claim itself offers little guidance, but the specification provides more direction. It teaches, “[t]he [G-CSF] dosage may depend on various factors such as mode of application, species, age, or individual condition. According to the invention, from 5 to 300 µg/kg/day of G- CSF sc.^[2] is applied.” Pai Decl. Ex. 1, ’427 Patent 3:4-7. G-CSF administration occurs “once per day over two to three days.” ’427 Patent 4:5-8. Amgen points to portions of the specification that explain, “[n]umerous substances” are capable of causing mobilization of blood-producing stem cells, such as G-CSF and “[s]ome chemotherapeutic agents.” ’427 Patent 1:32-37. These passages make clear that, at the time the patent was filed, skilled artisans knew G-CSF caused blood-producing stem cells to mobilize, and that any amount ranging from 5 to 300 µg/kg/day of G-CSF sc. would cause stem cells to mobilize enough to enable collection.

         The prosecution history of the ’427 patent offers skilled artisans further guidance and additional support for Amgen’s proposed construction. Three papers identified in the specification refer to various G-CSF dosage amounts within the range stated in the specification. Two papers examined the efficacy of subcutaneous doses of 10 µg/kg/day. Wu Decl. Ex 4 at 861 (Long et al., Cancer 76(5):860-68 (1995)); Wu Decl. Ex. 6 at 146 (Pierelli et al., J. Hematotherapy 2:145-53 (1993)). Another study tested the comparative potency of subcutaneous or intravenous doses of 10 µg/kg/day or 5 µg/kg/day. Wu Decl. Ex. 5 at 2177 (Nademanee et al., J. Clinical Oncology 12(10):2176-86 (1994)). These three studies supply a person skilled in the art with more information to determine with a reasonable degree of certainty how much G-CSF to administer to achieve more than a de minimus level of stem-cell mobilization.

         While the range of the amounts of G-CSF to administer is admittedly wide and variable depending on the size or species of the subject, a skilled artisan is not without any guidance to figure out how much G-CSF to administer. After all, “breadth is not indefiniteness.” SmithKline Beecham Corp. v. Apotex Corp., 403 F.3d 1331, 1341 (Fed. Cir. 2005). To the extent a skilled artisan may have difficulty adjusting the amount of G-CSF to administer depending on the species of the subject, the lack of precision in the claim and specification impacts only his or her ability to practice all embodiments of the claim-a question of enablement, not indefiniteness. See Takeda, 2014 WL 5862134, at *10 (citing Exxon Research & Eng’g Co. v. United States, 265 F.3d 1371, 1382 (Fed. Cir. 2001) (noting that “‘inoperable embodiments’ raise ‘an issue of enablement, and not indefiniteness”)). Overall, the patent communicates the purpose of G-CSF administration: to cause more than a de minimus number of blood-producing stem cells to enter the peripheral blood. While the claim and specification could have offered more precise guideposts, the disclosures provide those skilled in the art with sufficient information to figure out how to accomplish that goal. Accordingly, the phrase “hematopoietic stem cell mobilizing-effective amount of G-CSF” is not indefinite. It will be construed as follows: “an amount of G-CSF effective to mobilize hematopoietic stem cells.”

         2. “A method of treating a disease requiring peripheral stem cell transplantation in a patient in need of such treatment”

         The second phrase to construe is the preamble to claim 1. Although it appears in only claim 1, claims 2, 3, 4, and 6 incorporate the preamble by reference. Both parties agree the preamble limits the scope of the claim, but they disagree about how to construe it. The crux of the dispute is about the phrase “a method of treating a disease requiring peripheral stem cell transplantation in a patient in need of such treatment.” Amgen construes the phrase as follows: “In the practice of the method, a patient in need of a stem cell transplant receives a transplant of peripheral stem cells.” Sandoz offers the following construction: “In the practice of the method of treating a disease, a patient receives a transplant of peripheral stem cells.” The fight boils down to whether peripheral stem cell transplantation is itself disease treatment, or whether it is a component of disease treatment to alleviate the side effects of treatment (namely chemotherapy). The text of the claim itself and the intrinsic record support Sandoz’s construction.

         To begin, the phrase “such treatment” must have an antecedent. See Rapoport v. Dement, 254 F.3d 1053, 1059 (Fed. Cir. 2001) (noting the phrase “to a patient in need of such treatment” must have an antecedent basis). Sandoz argues the antecedent is “a method of treating a disease, ” whereas Amgen insists it refers back to “peripheral stem cell transplantation.” Under Sandoz’s construction, the treatment (usually chemotherapy) necessitates stem-cell transplantation. To practice the treatment method, the doctor mobilizes, collects, and transplants blood-producing stem cells into the patient. In contrast, under Amgen’s reading it is the disease (primarily cancer) that requires peripheral stem cell transplantation. While “such treatment” surely requires an antecedent, both proposed constructions are grammatically correct, and therefore to construe the terms requires a more searching inquiry.

         The text of the whole claim lends support to Sandoz’s construction. The method claim 1 includes two steps: (1) administration of G-CSF, and (2) administration of a chemotherapeutic agent. The claim describes the quantity of G-CSF to be administered as “stem cell mobilizing, ” whereas the chemotherapeutic agent is described as “disease treating.” See ’427 Patent at 10:26-29. In other words, one substance mobilizes stem cells, while the other treats a disease. The claim suggests the transplantation itself does not treat disease.

         The specification bears out this interpretation. It explains the purpose of the claimed method: “The use of high-dosage chemotherapy or bone marrow ablation by irradiation requires subsequent incorporation of hematopoietic stem cells into the patient, in which case recovery of such cells is required.” ’427 Patent at 1:18-21. Mobilization of blood-forming stem cells “has a crucial influence on the efficiency of” peripheral stem cell recovery. ’427 Patent at 1:22-24. The method claimed by the patent improves upon the process of collecting stem cells by increasing the number of stem cells in the peripheral blood, thereby reducing the number of leukaphereses required. See ’427 Patent at 1:24-27 (“At present, 2-3 leukaphereses are required for successful peripheral stem cell transplantation, resulting in considerable stress for the patients.”); id. at 1:55-61 (“As the required number of leukaphereses is extremely stressing for the patient in the run-up to the treatment of particular diseases, e.g., in preparing myeloablative or myelotoxic therapy, the invention was based on the object of achieving a superior yield of stem cells or a decrease in the number of leukophereses via enhanced mobilization of stem cells.”). Finally, the specification teaches that administration of G-CSF followed by administration of a chemotherapeutic agent is part of the “run-up to a, e.g. antitumor therapy, ” and therefore is not the disease treatment itself. ’427 Patent at 4:24-25.

         Thus, the specification clarifies any ambiguity in the text of the claim about whether peripheral stem-cell transplantation is a treatment for disease or a component of disease treatment.^[3] It is the latter. Accordingly, Sandoz has the better construction, and it is adopted.

         3. “disease treating-effective amount of at least one chemotherapeutic agent”

         The next phrase up for construction is “disease treating-effective amount of at least one chemotherapeutic agent.”^[4] It appears in claim 1, and the patentee also incorporated the term by reference into claims 2, 3, 4, and 6. Amgen proposes defining the phrase as “an amount of at least one chemotherapeutic agent sufficient to enhance the mobilization of stem cells for recovery from the blood for subsequent peripheral transplantation.” Sandoz offers the following construction: “an amount sufficient to treat a disease for which at least one chemotherapeutic agent is prescribed.” The crux of the dispute revolves around whether the chemotherapeutic agent treats a disease such as cancer (Sandoz’s construction), or whether the chemotherapeutic agent’s purpose is to mobilize blood-producing stem cells for collection and subsequent peripheral transplantation (Amgen’s construction). The text of the claim and the specification compel adoption of Sandoz’s proposal.

         “[T]he context in which a term is used in the asserted claim can be highly instructive.” Phillips, 415 F.3d at 1314. There are three parts to claim 1-the preamble and two limitations: the first limitation is a description of step one (administration of G-CSF); the second limitation is a description of step two (administration of the chemotherapeutic agent). Rather than referring to the two steps of the claimed process as “stem-cell mobilizing, ” the patentee chose to use different descriptors for G-CSF and chemotherapeutic agents. G-CSF is “hematopoietic stem cell mobilizing, ” whereas the chemotherapeutic agent is “disease treating.” See ’427 Patent at 10:27-29. “Different claim terms are presumed to have ...