Designing around patents with an immunotherapy case

Abstract

In TiVo Inc. V. EchoStar Corp case (2010), all judges of the US Court of Appeals for the Federal Circuit (CAFC) reemphasized that legitimate design around a competitor’s patents is always encouraged as a route of innovation. The modified elements of the design-around must be evaluated against the asserted claim(s) to ensure that each limitation is met before concluding that the modification is not substantially different from the previously adjudged infringed product. Regarding the significance of the differences between the features adjudged as infringement and the modified characteristics of the newly designed products, CAFC stated that the determination may refer to the rule of obviousness.

 

In this article, we present an immunotherapy case that shows how to overcome an obviousness rejection by showing an unexpected result. The new design using an anti-VEGF antibody-encoding sequence in vaccinia virus should significantly increase its therapeutic effect. Furthermore, the newly-designed virus would provide tumor-localized delivery of the antibody and enhance anti-tumor activity.

Keywords: :

• design-around
• immunotherapy
• obviousness
• patent
• virus

The patent system is organized to encourage innovation. A government grants the patentee the right to exclude others from practicing the technical development for a certain amount of time in return for fully disclosing the innovation. The government hopes that other inventors will learn from the disclosure, and use this knowledge as the basis for further innovation.

Inventors have legitimately designed around patents, building devices or designing pharmaceutical products or devising processes similar to, but not infringing upon, patent-protected inventions.^1,2 Our previous investigation³ demonstrated that avoiding all elements of a patent claim would be the first choice for designing around a patent. The prosecution history estoppel would be the second best option for avoiding patent infringement, and seeking to replace the non-equivalent element(s) would be another alternative for designing around a patent.

Another study⁴ further illustrated the designing-around procedures, starting with a thorough reading of the patent specification and prosecution history. The meaning of particular claim terms or the scope being disclaimed can be found in the written description that supports a claim.⁵ The patent specification offers explicit directions about claim meanings, and the patentee may act as his/her own lexicographer, and give a specialized definition of claim terms.⁶ Next, a design, device, or process can be developed by omitting a part or property from the claim, reversing the action(s) used in the claim, or changing the claim’s structure or range. Claims recite and define the structure or acts of an invention, and serve as tools to determine whether or not a patent is infringed.^3,7,8 Therefore, a modification as described above would, most likely, not be within the scope of the claim.

In TiVo Inc. V. EchoStar Corp,⁹ all judges of the CAFC made decisions on the issue related to designing around. Although the TiVo case is not related to biotech in particular, the rules laid down by the CAFC full court panel would be applicable to biotech, and of course to immunotherapy or vaccine-related research and development.

TiVo Inc. V. EchoStar Corp Case

TiVo Inc. owns US patent 6233389, which disclosures the digital video recorder technology allowing users to simultaneously record and play television broadcast sites. In 2004, Tivo sued EchoStar, claiming that their satellite television receivers infringe the hardware and software claims of the ‘389 patent. A district court entered judgment on the verdict and issued a permanent injunction against EchoStar. The injunction ordered EchoStar to stop making, using, offering to sell, and selling the receivers that were found infringing by the jury, and also to disable the digital video recorder functionality in existing receivers that had been placed with customers.

In 2008, CAFC affirmed the jury’s verdict that the EchoStar devices infringed the software claims of the ‘389 patent and remanded the district court to determine any additional damage that TiVo might have sustained. The injunction became effective around three months later.

EchoStar’s Designing-around

After losing a patent infringement action and being permanently enjoined from selling a product, EchoStar decided to design around the patent adjudged to have been infringed, but not to drop out of the market or to negotiate a license with the patentee. EchoStar claimed to have employed 15 engineers who put in 8000 h of labor over a year to design around the patented software. EchoStar redesigned one of their receivers by replacing the “star code detection” feature with a “statistical estimation” characteristic to seek the nonequivalent substitution³ of the “parsing” limitation in the claims. The start code detection feature designated the start of each video frame and indexed those codes to allow the system to locate and access a required frame from the data stream, while the statistical estimation characteristic relies on the statistics for average frame rate in order to estimate the location of a given video frame. Another design feature was to eliminate the “automatically flow controlled” limitation of claims to avoid all element rule.³

EchoStar further obtained an opinion of counsel that its modified software for digital video recorder was not infringing. EchoStar then deployed its designing-around receivers into the marketplace. However, TiVo moved the district court to find EchoStar in contempt of the injunction order. The district court held that EchoStar violated the order to stop selling infringing receivers and was in contempt for continuing to use the functionality of the digital video recorder.

CAFC Full Court Opinions

The CAFC first cited the US Supreme Court precedent that a lack of intent to violate an injunction alone cannot save an infringer from a finding of contempt. The general rule in civil contempt is that a party need not intend to violate an injunction to be found in contempt.¹⁰ Therefore, CAFC affirmed that the district court was correct in rejecting EchoStar’s diligence and good-faith efforts arguments in deciding whether a violation had occurred.

Furthermore, CAFC stated that a patentee seeking to enforce the injunction must prove both that the newly accused product is not substantially different from the product originally found to infringe and that the newly accused product actually infringes.¹¹ The US Supreme Court also reminded that contempt is a serve remedy and should not be resorted to where there is a fair ground of doubt as to the wrongfulness of the defendant’s conduct.¹² Therefore, CAFC vacated the judgment of the district court that focused solely on infringement by the newly accused devices in deciding contempt.

Indeed, CAFC requires that the contempt analysis must focus on the differences between the features previously adjudged as infringing and the modified characteristics of the newly designed products. Specifically, when the new designing-around has modified or removed one or more elements previously found to infringe, the court must take an inquiry into whether the modification is significant. If the modification is significant, the newly accused product as a whole shall be judged as substantially different from the previously adjudged infringing one. When there is a more than an intangible difference, a contempt order is considered inappropriate.¹³

Regarding the significance of the differences between the features adjudged as infringing and the modified characteristics of the newly accused products, CAFC stated that the determination may refer to the rule of obviousness¹⁴ in contempt proceedings. The main issue is to determine whether the modification employs or combines elements already known in the prior art that would be obvious to a person of ordinary skill in the art at the time of the modification. An obvious modification may be more like an intangible difference and vice versa. However, CAFC disagreed that a redesign that substitutes a patent element with a patented subject serves as prima facie evidence of an intangible difference.

In this full court case, CAFC further emphasized that legitimate design around a competitor’s patent is always encouraged as a route of innovation. Thus, CAFC requires an evaluation of the modified elements of the modification against the asserted claim in order to ensure that each limitation continue to be met before concluding that the modification is not substantially different from the previously adjudged infringing product. Certainly, the patentee bears the burden of proving intangible difference and infringement.

An Immunotherapy Example

The single-chain antibodies (scFv V65) against vascular endothelial growth factor (VEGF) were demonstrated to reduce tumor growth in mice. Systemic administration of an adenovirus expression vector for delivering anti-VEGF scFv V65 would produce a sustained and improved inhibitory effect for tumor growth.¹⁵ Szalay et al.¹⁶ used microorganisms or cells containing heterologous DNA, polypeptides or RNA to induce immunization of an organism against a tumor and demonstrated the tumor accumulation properties of a recombinant vaccinia virus (strain Lister) from the Institute of Viral Preparations in Moscow, Russia (LIVP) with an insertion in the F3 gene for purposes of tumor therapy.

Recombinant humanized anti-VEGF F(ab) and IgG1 variants were found to bind VEGF with affinities very similar to that of the original murine monoclonal antibody (mAb). Moreover, the recombinant humanized anti-VEGF mAb would inhibit VEGF-induced proliferation of endothelial cells in vitro and of tumor growth in vivo.¹⁷ Another invention¹⁸ provided novel antibodies and polypeptide sequences capable of binding to rodent VEGF and human VEGF with K_d values within ten-fold of each value and capable of inhibiting the binding of VEGF to a VEGF receptor.

References taught feasibility and an advantage of using scFV against VEGF to treat cancer in combination with chemotherapy or radiation therapy, especially because scFV was found to be sustainably expressed and could be delivered in vivo for treating a cancer. However, none of the references suggested that the LIVP virus modified to express an anti-VEGF antibody would be more effective than other virus vectors. Furthermore, the engineered LIVP strain would accumulate in the tumor and thus provide expression and delivery of the anti-VEGF antibody in the tumor. The design-around with the engineered LIVP virus comprises an inactivated gene locus, that of the thymidine kinase (TK) gene or of the F14.5L gene. The gene for the anti-VEGF antibody or fragment would be inserted into a non-essential locus in the virus operatively linked to a promoter for expression. The virus would permit tumor-specific locally amplified drug delivery.

In the TiVo Inc. V. EchoStar Corp case, a full court CAFC reemphasized that legitimate design around a competitor’s patents is always encouraged. The main issue is to determine whether the modification is substantially different from that in the original patent claim. The modification of LIVP virus to include an anti-VEGF antibody would be more effective than with other viruses. The newly designed viruses would provide tumor-localized delivery of the antibody and enhanced anti-tumor activity. Thus, the difference between the design-around and prior references would be significant.

Conclusion

In TiVo Inc. V. EchoStar Corp,⁹ a CAFC full court judge panel reemphasized that designing around patent claims to achieve a non-infringing product or method is one of the benefits of patent system.^1,19 Even under an injunction order to stop making, using, offering to sell, and selling the infringed products, the defendant could still design around the patent claims. The contempt analysis must focus on the difference between the features adjudged as infringing and the modified characteristics of the newly accused products, but not solely on infringement by the newly accused devices.

CAFC requires the evaluation of the modified elements of the new design-around against the asserted claim in order to ensure that each limitation continues to be met, and the patentee bears the burden of proving intangible difference and infringement. This CAFC decision would further confirm part of the designing-around guideline,³ including lack of conforming to all elements of a patent claim, prosecution history estoppel, nonequivalent substitution, and reconstruction.

Furthermore, an immunotherapy case is described that involves a vaccinia virus encoding an anti-VEGF antibody to increase its therapeutic effect. The newly designed viruses would provide tumor-localized delivery of the antibody and thus enhance its anti-tumor activity. These unexpected results would demonstrate the differences between the features adjudged as infringing and the modified characteristics of the new designs.