Case: 23-1389   Document: 67    Page: 1     Filed: 02/07/2025




   United States Court of Appeals
       for the Federal Circuit
                 ______________________

  WUHAN HEALTHGEN BIOTECHNOLOGY CORP.,
                Appellant

                           v.

      INTERNATIONAL TRADE COMMISSION,
                  Appellee

            VENTRIA BIOSCIENCE INC.,
                     Intervenor
               ______________________

                       2023-1389
                 ______________________

    Appeal from the United States International Trade
 Commission in Investigation No. 337-TA-1238.
                 ______________________

                Decided: February 7, 2025
                 ______________________

     ERIK R. PUKNYS, Finnegan, Henderson, Farabow, Gar-
 rett & Dunner, LLP, Washington, DC, argued for appel-
 lant. Also represented by J. MICHAEL JAKES, RYAN
 VALENTINE MCDONNELL, ELIZABETH NIEMEYER, JASON LEE
 ROMRELL; MICHAEL KUDRAVETZ, Boston, MA.

    RONALD TRAUD, Office of the General Counsel, United
 States International Trade Commission, Washington, DC,
 argued for appellee. Also represented by DOMINIC L.
 BIANCHI, WAYNE W. HERRINGTON.
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 2              WUHAN HEALTHGEN BIOTECHNOLOGY CORP. v. ITC




    THOMAS P. HENEGHAN, Husch Blackwell LLP, Madison,
 WI, argued for intervenor. Also represented by JENNIFER
 E. HOEKEL, St. Louis, MO; BEAU JACKSON, Kansas City,
 MO; MATTHEW KAMPS, Chicago, IL.
                  ______________________

     Before MOORE, Chief Judge, CHEN, Circuit Judge, and
                 MURPHY, District Judge. 1
 MOORE, Chief Judge.
     Wuhan Healthgen Biotechnology Corp. (Healthgen)
 appeals a final determination from the International Trade
 Commission (Commission) finding (1) Healthgen’s clinical
 grade albumin products infringe claims 1 and 11–13 of 

; and (2) Intervenor Ventria Biosci-
 ence Inc. (Ventria) satisfied the economic prong of the do-
 mestic industry requirement under subparagraph (a)(3) of
 

 (Section 337). Because substantial evi-
 dence supports the Commission’s findings, we affirm.
                        BACKGROUND
     Cell culture media supplies essential nutrients for cells
 to grow in an artificial environment. This media often con-
 tains albumin, a protein produced in an animal’s liver,
 which raises contamination and ethical concerns. As a re-
 sult, recombinant albumin has been used as an alternative.
 Recombinant technology involves inserting a gene of inter-
 est into a host cell to produce a desired protein the cell
 would not normally produce, allowing for large-scale pro-
 duction of proteins without relying on animal sources.




      1   Honorable John F. Murphy, District Judge, United
 States District Court for the Eastern District of Pennsylva-
 nia, sitting by designation.
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 WUHAN HEALTHGEN BIOTECHNOLOGY CORP. v. ITC                  3



      Ventria owns the ’951 patent, which is directed, in part,
 to cell culture media containing recombinant human serum
 albumin (rHSA) produced in a genetically modified plant.
 ’951 patent at 31:37–41, 39:11–13. Claim 1 is representa-
 tive and recites:
     1. A cell culture media supplement or complete me-
     dia composition for improving the growth of a cell
     in cell culture comprising:
     a recombinant mammalian albumin wherein said
     albumin is:
         i) produced in a transgenic plant;
         ii) has less than 1 EU of endotoxin/mg of albu-
         min; and
         iii) less than 2% aggregated albumin.
 

 at 123:44–51 (emphasis added).
     Healthgen imports clinical and medium grade rHSA
 products. Ventria filed a complaint with the Commission
 alleging Healthgen’s importation activities violated § 337
 because its imported products infringed the ’951 patent.
 Ventria relied on its six rHSA products—Cellastim, Exbu-
 min, OptiPEAK, OptiVERO, ITSE+A, and Optibumin—to
 satisfy the economic prong of the domestic industry re-
 quirement and asserted all six products practice the ’951
 patent.
      The Commission instituted an investigation, and the
 Administrative Law Judge (ALJ) issued an initial determi-
 nation finding Healthgen violated § 337 by importing clin-
 ical and medium grade rHSA products that infringe claims
 1 and 11–13 of the ’951 patent. J.A. 145–68. The ALJ also
 found Ventria satisfied the domestic industry requirement
 under subsections (A), (B), and (C) of § 337(a)(3) based on
 all six rHSA products and, in the alternative, based on
 Optibumin alone. J.A. 211–22.
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 4              WUHAN HEALTHGEN BIOTECHNOLOGY CORP. v. ITC




     Healthgen petitioned the Commission for review. The
 Commission affirmed the ALJ’s finding of infringement as
 to Healthgen’s clinical grade products, but not its medium
 grade products. J.A. 25–53. The Commission affirmed the
 ALJ’s finding that Ventria satisfied the domestic industry
 requirement based on Optibumin alone without further
 analysis, but took no position on Ventria’s five other rHSA
 products. J.A. 54–55.
    Healthgen appeals. We have jurisdiction pursuant to
 

(a)(6).
                           DISCUSSION
                      I.   Infringement
      We review the Commission’s legal conclusions de novo
 and its factual findings for substantial evidence. Roku, Inc.
 v. Int’l Trade Comm’n, 

 (Fed. Cir. 2024).
 Infringement is a question of fact. Kinik Co. v. Int’l Trade
 Comm’n, 

 (Fed. Cir. 2004).
     The Commission found 2 Healthgen’s clinical grade
 products infringe the ’951 patent because they contain less
 than 2% aggregated albumin. J.A. 17–19, 27–32. The
 Commission relied on Healthgen’s SEC-HPLC 3 data,
 which show the products had at most 1.1% aggregated al-
 bumin. J.A. 3371–72.




     2   We refer to the findings on review in the Infringe-
 ment and Domestic Industry sections as those of the Com-
 mission, whether made by the ALJ or the Commission,
 because the Commission adopted the ALJ’s findings not in-
 consistent with the Commission’s opinion. J.A. 4.

     3   SEC-HPLC (Size Exclusion Chromatography High
 Performance Liquid Chromatography) is a technique used
 to separate proteins based on their size. J.A. 17.
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 WUHAN HEALTHGEN BIOTECHNOLOGY CORP. v. ITC                 5



      Healthgen argues the Commission erred in relying on
 SEC-HPLC data because the data does not reflect aggre-
 gated albumin levels at the time of importation. Appel-
 lant’s Br. 44–51. Rather, the data, measured in China one
 day after manufacture, reflects when aggregated albumin
 is lowest and fails to account for increased aggregation dur-
 ing storage and shipping such that the products are no
 longer infringing upon importation. 

     The Commission’s finding is supported by substantial
 evidence. It is undisputed SEC-HPLC is a reliable and ap-
 propriate test to measure aggregation levels and the meas-
 ured 1.1% aggregated albumin meets the “less than 2%
 aggregated albumin” claim limitation. Appellant’s Br. 12,
 48; Appellee’s Br. 16. The Commission found aggregated
 albumin levels in Healthgen’s products do not increase
 above 2% during storage and shipping. J.A. 29–30, 36–37;
 J.A. 161. This finding is supported by expert testimony
 that neither storage alone nor shipment according to com-
 mon practice would induce additional aggregation, J.A.
 1453 at 452:5–16, peer-reviewed literature discussing ag-
 gregation increase under extreme stressor conditions, J.A.
 3380, and Healthgen’s communications to customers ex-
 plaining stability test results show its products remain sta-
 ble under its storage and shipping practices, see, e.g., J.A.
 3137–39; J.A. 5035; J.A. 7029.
     Healthgen contends the peer-reviewed literature sug-
 gests aggregation is caused by storage and shipping, and
 its communications to customers are about stability and
 quality which are untethered to the “less than 2% aggre-
 gated albumin” limitation. Appellant’s Br. 46–47, 49–50.
 Even accepting Healthgen’s claim that aggregated albumin
 levels do increase, Healthgen did not show this aggregation
 would rise to noninfringing levels before importation. Ap-
 pellant’s Br. 48–49 (claiming aggregated albumin in-
 creased to greater than 2%, despite acknowledging “it is
 unclear precisely how much it had increased upon the prod-
 uct’s arrival in the United States”). Healthgen’s most
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 6              WUHAN HEALTHGEN BIOTECHNOLOGY CORP. v. ITC




 concrete evidence for increased aggregated albumin is com-
 paring SEC-HPLC data taken in September 2020 with Re-
 ducing SDS-PAGE 4 data taken in June 2021. Id.; compare
 J.A. 3372, with J.A. 3297. The same batch that measured
 1.1% aggregated albumin in China using SEC-HPLC meas-
 ured 1.81% nine months later in the United States using
 Reducing SDS-PAGE. J.A. 3372; J.A. 3297. However, the
 Reducing SDS-PAGE data is not inconsistent with a find-
 ing that the imported products are infringing because
 1.81% aggregated albumin still meets the “less than 2% ag-
 gregated albumin” limitation. There is thus substantial ev-
 idence for the Commission’s finding of noninfringement.
 Spansion, Inc. v. Int’l Trade Comm’n, 

 (Fed. Cir. 2010) (“[We] must affirm a Commission determi-
 nation if it is reasonable and supported by the record as a
 whole, even if some evidence detracts from the Commis-
 sion’s conclusion.” (quoting Nippon Steel Corp. v. United
 States, 

 (Fed. Cir. 2006) (internal quo-
 tation marks omitted))).
     The Commission also relied on Reducing SDS-PAGE
 data as an alternative basis for finding infringement. J.A.
 19–25, 32–36. Because we affirm the finding of infringe-
 ment based on SEC-HPLC data, we need not reach the
 Commission’s alternative basis.




     4    Similar to SEC-HPLC, Reducing SDS-PAGE (So-
 dium Dodecyl Sulfate Polyacrylamide Gel Electrophoresis)
 is a technique used to separate proteins based on their size.
 J.A. 19–20. But unlike SEC-HPLC, Reducing SDS-PAGE
 alters the sample before analysis by first using a surfactant
 (SDS) to denature the proteins and then using a reducing
 agent to break the disulfide bonds holding protein subunits
 together. J.A. 20, 24.
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 WUHAN HEALTHGEN BIOTECHNOLOGY CORP. v. ITC                    7



                     II.    Domestic Industry
     Whether the domestic industry requirement is satis-
 fied “typically presents issues of both law and fact.” John
 Mezzalingua Assocs., Inc. v. Int’l Trade Comm’n, 

 (Fed. Cir. 2011). Whether investments are
 “substantial” enough to satisfy this requirement is a ques-
 tion of fact. 

 We review the Commission’s substantiality
 finding for substantial evidence. Roku, 

.
      To demonstrate a patent infringement-based violation
 of § 337, a complainant must show “an industry in the
 United States, relating to the articles protected by the pa-
 tent . . . exists or is in the process of being established.” 

(a)(2). This domestic industry requirement
 has a technical prong and an economic prong. InterDigital
 Commc’ns, LLC v. Int’l Trade Comm’n, 

 (Fed. Cir. 2013). Healthgen conceded Optibumin practices
 the ’951 patent and thus satisfies the technical prong. Ap-
 pellant’s Br. 64; J.A. 54. The economic prong considers
 whether “there is in the United States, with respect to the
 articles protected by the patent, . . . (A) significant invest-
 ment in plant and equipment; (B) significant employment
 of labor or capital; or (C) substantial investment in its ex-
 ploitation, including engineering, research and develop-
 ment, or licensing.” 

(a)(3). Only one of
 subsections (A), (B), or (C) needs to be satisfied to meet the
 economic prong. Roku, 

 n.1. A “quantita-
 tive analysis” is required to determine whether invest-
 ments are “significant.” Lelo Inc. v. Int’l Trade Comm’n,
 

 (Fed. Cir. 2015).
     The Commission found Ventria’s Optibumin invest-
 ments in plant and equipment costs under subsection (A),
 labor costs under subsection (B), and research and devel-
 opment costs under subsection (C) are significant and sub-
 stantial because, inter alia, 100% of those investments
 occur in the United States. J.A. 54; J.A. 219–20. A sales-
 based allocation method was used to calculate the
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 8              WUHAN HEALTHGEN BIOTECHNOLOGY CORP. v. ITC




 investments under each subsection. J.A. 211–12. The
 Commission also found Ventria’s Optibumin investments
 are significant and substantial based on a comparison of
 the investments to Optibumin’s revenue. J.A. 54; J.A. 220.
 Healthgen argues Ventria’s Optibumin investments are
 too small to be significant or substantial under § 337(a)(3),
 and low Optibumin revenue, when coupled with small in-
 vestments, artificially creates high investment-to-revenue
 ratios. Appellant’s Br. 64–73.
      The Commission’s findings are supported by substan-
 tial evidence. That it may have been relatively inexpensive
 for Ventria to develop and produce its patented product
 does not alone preclude a finding that Ventria did in fact
 establish a domestic industry in that product. It is undis-
 puted all of Ventria’s investments and activities related to
 researching, developing, and commercially producing Opti-
 bumin occurred within the United States. Appellant’s Br.
 68–69; Appellee’s Br. 36–37. Comparing the cost of foreign
 to domestic manufacturing to determine the percentage of
 additional value created by domestic Optibumin operations
 in the final product yields a value added of 100%. J.A. 219–
 20. The investment-to-revenue ratio can indicate whether
 an investment is significant and substantial. A high ratio
 signals the company is investing heavily in the industry
 despite comparatively low revenue, highlighting the indus-
 try’s importance and value to the company, which can be
 predictive of a significant market. See, e.g., J.A. 1699 at
 697:5–17; J.A. 220–21.
     Healthgen contends the Commission relies on qualita-
 tive factors to overcome Ventria’s quantitatively small
 Optibumin investments in violation of our precedent. Ap-
 pellant’s Br. 64–65, 67–69; see also Lelo, 

 (“Qualitative factors cannot compensate for quantitative
 data that indicate insignificant investment and employ-
 ment.”). We do not agree. In Lelo, we recognized the com-
 parison of domestic investments to total (i.e., domestic plus
 foreign) investments as a valid quantitative analysis for
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 WUHAN HEALTHGEN BIOTECHNOLOGY CORP. v. ITC                 9



 assessing the significance of investments. 786 F.3d at 883–
 84 (citing Certain Concealed Cabinet Hinges and Mounting
 Plates, Inv. No. 337-TA-289, 

, Comm’n
 Op. at 11–12 (Jan. 8, 1990)). We also recognized the value
 added by domestic operations as a quantitative factor in
 the assessment. 

 at 884 (citing Certain Male Prophylac-
 tic Devices, Inv. No. 337-TA-546, USITC Pub. 4005,
 Comm’n Op. at 24–26 (June 21, 2007)).
     Small market segments can still be significant and sub-
 stantial enough to satisfy the domestic industry require-
 ment. A finding of domestic industry cannot hinge on a
 threshold dollar value or require a rigid formula; rather,
 the analysis requires a holistic review of all relevant con-
 siderations that is very context dependent. Bally/Midway
 Mfg. Co. v. Int’l Trade Comm’n, 

 (Fed.
 Cir. 1983) (“There is nothing in the statute which requires
 that an industry must be of any particular size.” (cleaned
 up)); Certain Printing and Imaging Devices, Inv. No. 337-
 TA-690, 

, Comm’n Op. at 27 (Feb. 17,
 2011) (explaining whether investment activities are signif-
 icant or substantial “is not evaluated according to any rigid
 mathematical formula,” but rather requires “an examina-
 tion of the facts in each investigation, the article of com-
 merce, and the realities of the marketplace”); 134 CONG.
 REC. S10711-01, 

 (Aug. 3, 1988) (“Smaller
 businesses should not be denied the right to seek relief
 merely because they may have made smaller financial in-
 vestments than large companies . . . .”). Though the dollar
 amounts of Ventria’s Optibumin investments are small,
 the Commission found all of the investments are domestic,
 all market activities occur within the United States, and
 the high investment-to-revenue ratios indicate this is a val-
 uable market. J.A. 219–21. Under these circumstances,
 there is substantial evidence for the Commission’s finding
 that the domestic industry requirement is satisfied.
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 10             WUHAN HEALTHGEN BIOTECHNOLOGY CORP. v. ITC




                        CONCLUSION
    We have considered Healthgen’s remaining arguments
 and find them unpersuasive. For the reasons given above,
 we affirm.
                        AFFIRMED