A Study of Post-Grant Reviews in U.S. PTO Tech Center 1600

Post grant review (PGR) is a trial proceeding conducted at the Patent Trial and Appeal Board (PTAB or Board) to review the patentability of one or more claims in a patent on any ground that could be raised under 35 U.S.C. §282(b)(2) or (3) (e.g., §§101, 102, 103 or 112). The procedure for conducting post grant review took effect on September 16, 2012, and generally applies to patents issuing from applications subject to first-inventor-to-file provisions of the American Invents Act.

The PGR process begins with a third party filing a petition on or prior to the date that is 9 months after the grant of the patent or issuance of a reissue patent. The patent owner may file a preliminary response to the petition. A PGR may be instituted upon a showing that, it is more likely than not that at least one claim challenged is unpatentable. If the proceeding is instituted and not dismissed, a final determination by the PTAB will be issued within 1 year (extendable for good cause by 6 months).

We have been monitoring the PGRs filed in U.S. PTO Tech Center (TC) 1600 and a summary of the PGRs filed to date is shown in the attached table: PGRCHARTTC1600_09_28_2018.  We will continue to update this table in future posts as new PGRs are filed against patents issued from this TC.

As of September 27, 2018, 39 PGRs have been filed in TC 1600.  Twenty-three of these PGRs have involved transitional applications.  Five different drugs listed in the electronic Orange Book have been the subject of one or more PGRs (namely, Aloxi®, phenylephrine hydrochloride, Copaxone®, Jakafi® and Qbrelis®).

A summary of the grounds alleged in the 39 PGRs is provided in the below table.

§101
§101* (Other)
§112 (Written Description)
§112 (Enablement)
§112 (Indefiniteness)
§102
§103

4

2 28 25 15 27

27

*Other grounds raised under §101 included lack of inventorship and practical utility.

A summary of the status of the 39 PGRs is provided in the below table.

Terminated
Institution Denied
Trial Instituted
Final Written Decision
Pending
7
13
4
4
11

The four written decisions issued thus far have been in Altaire Pharmaceuticals, Inc. v. Paragon BioTeck, Inc. (PGR2015-00011), Grünenthal GmBH v. Antecip Bioventures II LLC (PGR2017-0008), L’Oréal USA, Inc. v. Liqwd, Inc. (PGR2017-00012) and KVK-Tech, Inc. v. Silvergate Pharmaceuticals, Inc. (PGR2017-00039).   A brief summary of each of the final written decisions is provided in the attached table.  Particularly noteworthy is the decision in Grünenthal which is the first final written decision involving a patent in TC 1600 that focuses solely on written description.  This decision is helpful in that it provides insight on how the PTAB analyzes written description in such proceedings.  Given its importance, Grünenthal is discussed in more detail below.

Grünenthal GmBH v. Antecip Bioventures II LLC

Grünenthal requested post-grant review of claims 1-17 of U.S. Patent No. 9,283,239 (the ‘239 patent) owned by Antecip.  In a final written decision entered on June 22, 2018, the PTAB held that Grünenthal had demonstrated by a preponderance of the evidence that claims 1-17 of the ‘239 patent were unpatentable for a lack of written description.

Background

The ‘239 patent is directed to oral dosage forms of bisphosphonate compounds, such as zoledronic acid, that can be used to alleviate pain or related conditions.  One such condition, complex regional pain syndrome (CRPS), is a debilitating pain syndrome that is characterized by severe pain in a limb that is accompanied by edema, and autonomic, motor and sensory changes.  Because bisphosphonates generally have low oral bioavailability, the ‘239 patent describes enhancing oral bioavailability of zoledronic acid by administering the compound in its disodium salt form.

Claims of the ‘293 patent

The ‘293 patent issued with 17 claims.  Claim 1, the only independent claim, is reproduced below:

  1. A method of treating complex regional pain syndrome comprising orally administering zoledronic acid to a human being in need thereof, wherein the human being receives about 80 to about 500 mg of zoledronic acid within a period of six months.

Dependent claim 17, which also discussed in the PTAB’s decision, is reproduced below:

  1. The method of claim 1, wherein the zoledronic acid is orally administered in a dosage form containing at least 10% zoledronic acid.

Written Description of the ‘293 patent

According to the specification, the monthly dose of zoledronic acid:

. . . is about 5000 mg or less, about 4000 mg or less, about 3000 mg or less, about 2000 mg or less, about 1000 mg or less, about 700 mg or less, about 600 mg or less, about 1 mg to about 4,000 mg, about 1 mg to about 1,000 mg, about 10 mg to about 1000 mg, about 50 mg to about 1000 mg, about 10 mg to about 600 mg, about 40 mg to about 600 mg, about 50 mg to about 600 mg, or about 100 mg to about 600 mg, about 40 mg to about 2000 mg, about 40 mg to about 800 mg, about 50 mg to about 800 mg, or about 100 mg to about 800 mg, about 40 mg to about 1000 mg, about 50 mg to about 1000 mg, or about 100 mg to about 1000 mg, or any monthly dose in a range bounded by, or between, any of these values.  Column 11, lines 33-48.

…may be administered for only 1 month, or may be repeatedly administered for 2 or more months.  Column 12, lines 2-3.

Additionally, the specification, in column 10, lines 40-63, provides following guidance with regard to dosing regimens:

Any suitable amount of zoledronic acid may be used. Some solid or liquid oral dosage forms, or units of oral dosage forms (referred to collectively herein as ‘oral dosage form(s)’) may contain about 0.005 mg to about 20 mg, about 0.1 mg to about 10 mg, about 0.5 mg to about 10 mg, about 0.2 mg to about 5 mg, about 1 mg to about 500 mg, about 1 mg to about 50 mg, about 10 mg to about 250 mg, about 100 mg to about 300 mg, about 20 mg to about 200 mg, about 20 mg to about 150 mg, about 30 mg to about 100 mg, about 1 mg to about 1,000 mg, about 10 mg to about 50 mg, about 10 mg to about 300 mg, about 10 mg to about 150 mg, about 10 mg to about 100 mg, about 40 mg to about 150 mg, about 10 mg to about 600 mg, about 40 mg to about 600 mg, about 40 mg to about 2000 mg, about 40 mg to about 800 mg, about 25 mg to about 800 mg, about 30 mg to about 800 mg, about 10 mg to about 500 mg, about 50 mg to about 150 mg, about 50 mg, about 100 mg, about 50 mg to about 500 mg, about 100 mg to about 2000 mg, about 300 mg to about 1500 mg, about 200 mg to about 1000 mg, about 100 mg to about 500 mg, or about 150 mg of zoledronic acid, or any amount of zoledronic in a range bounded by, or between, any of these values. In some embodiments, the oral zoledronic acid is administered daily, weekly, monthly, every two or three months, once a year, or twice a year. (Emphasis added).

Moreover, the specification in column 13, lines 34-40, provides the following guidance with regard to dosing regimens:

In some embodiments, an oral dosage form comprises about 10 mg to about 150 mg or about 10 mg to about 100 mg of zoledronic acid, and is administered daily for about 5 to about 10 consecutive days. This regimen may be repeated once monthly, once every two months, once every three months, once every four months, once every five months, once every six months, once yearly, or once every two years. (Emphasis added).

With respect to the examples, example 3 describes treatment of CRPS with orally administered zoledronic acid in a rat tibia fracture model. According to this example, CRPS was induced by fracturing the right distal tibias of the animals, then casting the fractured hindpaws for four weeks. The animals were orally administered either a vehicle (control) or 18 mg/m2/day of zoledronic acid for 28 days. After 28 days, the casts were removed and the animals tested for hindpaw pain, edema, and warmth.  Additionally, Figures 3–6 depict the results of the treatment. The ’239 patent states that “a daily dose of 18 mg/m2 corresponds to a monthly dose of about 500–560 mg/m2 or a human dose of about 800–900 mg”.

PTAB’s Analysis and Decision

Claim 1 – “about 80 to about 500 mg of zoledronic acid within a period of six months”

The PTAB first considered whether the specification provided written description support for the range of “about 80 to about 500 mg of zoledronic acid” as recited in the claims.  The PTAB acknowledged the Antecip’s argument that column 10 of the ’239 patent specification disclosed ranges that would encompass the claimed range.   Specifically, the PTAB noted that this portion of the specification disclosed the range of “about 50 mg to about 500 mg,” thereby giving literal support to the range and to the endpoint of “about 500 mg.”  The Board also noted that although the endpoint of “about 80 mg” was not expressly disclosed in combination with the 500 mg endpoint, that the Federal Circuit had explained

If lack of literal support alone were enough to support a rejection under § 112, then the statement of In re Lukach . . . that ‘the invention claimed does not have to be described in ipsis verbis in order to satisfy the description requirement of § 112,’ is empty verbiage.

Thus, according to the PTAB, the issue was whether the description “clearly allowed persons of ordinary skill in the art to recognize” the claimed invention.  The PTAB stated that in this case, the ’239 patent specification clearly did not allow persons of ordinary skill in the art to recognize the “about 80 mg” endpoint as part of invention described in the ’239 patent.  Specifically, the Board noted that there was no disclosure of “about 80 mg” as a preferred endpoint, no disclosure of a specific embodiment including a dose of 80 mg, nor any other description suggesting the importance or criticality of the “about 80 mg” endpoint.

As a result, the Board concluded:

In view of the lack of any explicit disclosure for ‘about 80 mg’ endpoint, Patent Owner suggests that the ‘about 80 mg’ endpoint may be derived from the specification in numerous ways. PO Resp. 13–33; Ex. 2015 ¶¶ 26, 28. For example, Patent Owner argues that the endpoint of 80 mg finds support in column 13 of the specification, which discloses a range of ‘about 10 mg to about 100 mg’ administered over the course of 5 to 10 consecutive days, thereby essentially disclosing a list six different ranges that includes the ranges of about 50 mg to about 500 mg and about 80 mg to about 800 mg. PO Resp. 14 (citing Ex. 2015 ¶¶ 18, 26–29); Tr. 24:8–25:7, 30:16–33:11, 45:3–46:22.

We are aware of cases indicating that the written description analysis requires consideration as to whether one of skill in the art could derive the claimed ranges from the specification. See e.g., Purdue Pharma L.P. v. Faulding Inc., 230 F.3d at 1327; Vas–Cath Inc. v. Mahurkar, 935 F.2d at 1563–64; Ralston Purina Co. v. Far–Mar–Co, Inc., 772 F.2d at 1575; In re Wertheim, 541 F.2d at 264–65. For example, we note that ‘ranges found in applicant’s claims need not correspond exactly to those disclosed in [the specification, so long as] one skilled in the art could derive the claimed ranges from the  [ ] disclosure’. Vas–Cath, 935 F.2d at 1566. However, none of the cases concluding that sufficient written description existed such that a person of ordinary skill in the art could derive a claimed range from a specification are factually equivalent to the present case, where, as here, a non-original claim recites a dosage regimen range with endpoints derived from an inordinate amount of picking and choosing from disparate disclosures of various embodiments reciting broader ranges. For example, in Ralston, the Federal Circuit held that the disclosure of 25%–27% water in a soybean mixture did not support broader claims to ‘at least 20%’, ‘between 20% and 40%’, or ‘in the range of 20%–30%’ moisture levels, but did support moisture levels of ‘at least about 25% by weight’ and ‘at least 25% by weight’, reasoning that the open-ended claims would be limited by what a person skilled in the art would understand to be workable. 772 F.2d at 1576; see also, In re Wertheim, 541 F.2d at 264–65 (discussed hereinabove).

Furthermore, we note that the disparate disclosures of the ’239 patent specification upon which Patent Owner relies may very well render the ‘about 80 mg’ endpoint of the claimed ranges obvious to a person having ordinary skill in the art. Obviousness, however, is an inappropriate standard to measure a claim’s compliance with the description requirement. Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572 (Fed. Cir. 1997) (‘One shows that one is ‘in possession’ of the invention by describing the invention, with all its claimed limitations, not that which makes it obvious’.) Moreover, we note that the claims do not merely require administration of a dose of about 80 mg to about 500 mg of zoledronic acid, they also require that dose to be administered ‘within a six month period’.  The ’239 patent specification does not use the phrase ‘within a six month period’, but rather discloses that the various described dosage amounts may be administered, for example, ‘monthly, every two or three months, once a year, or twice a year’ or may be ‘repeated . . . once every six months’.  Ex. 1003, 10:40–63, 13:27–33. To the extent the specification does describe periods of six months, it also does not specify the administration of the recited doses over six months. Thus, a person of ordinary skill in the art must further derive from the language of the ’239 patent specification the time frame of ‘within a period of six months’ to administer the recited dose of ‘about 80 to about 500 mg of zoledronic acid’, thereby further complicating the process necessary to derive the recited dosing regimen from the ’239 patent specification. We thus, conclude that the ’239 patent specification does not clearly allow persons of ordinary skill in the art to recognize nor derive the recited dosing regimen of ‘about 80 to about 500 mg of zoledronic acid within a period of six months’.  (Emphasis added).

Claim 17 – “orally administered in a dosage form containing at least 10% zoledronic acid”

With respect to claim 17, Grünenthal acknowledged that the ’239 patent described liquid compositions containing from 0.0001 % to about 50% (w/v) zoledronic acid, and solid compositions containing from 5% up to about 90% (w/w) zoledronic acid.  However, Grünenthal argued that because formulations containing more than 90% zoledronic acid were not described in the specification but would be within the scope of claim 17, the written description requirement was not satisfied.  Interestingly, Antecip did not specifically address Grünenthal’s arguments regarding claim 17. Nonetheless, the PTAB was not persuaded by Grünenthal’s contentions. Instead, it found that the ’239 patent contained a sufficient written description of an oral dosage form containing “at least 10% zoledronic acid”.  Specifically, according to the PTAB, the specification described a “full panoply of zoledronic acid concentrations” citing to column 10, lines 17-28 which recited that the liquid compositions may contain:

…about 10% (w/v) to about 15% (w/v), about 15% (w/v) to about 20% (w/v), about 20% (w/v) to about 30% (w/v), about 30% (w/v) to about 40% (w/v), or about 40% (w/v) to about 50% (w/v) of zoledronic acid.

Additionally, with respect to solid dosage forms, the PTAB referred to column 10, lines 29-32 which recited that such solid forms “may contain at least about 10% (w/w), at least about 20% (w/w) . . .” up to “at least about 80% [w/w]” zoledronic acid.  Moreover, solid dosage forms were also described in this same section of the specification as containing zoledronic acid in ranges beginning from “about 10% (w/w) to about 30% (w/w), about 10% (w/w) to about 20% (w/w) . . .” all the way up to a range of “about 80% (w/w) to about 90% (w/w)” (See, column 10, lines 32-39).  Therefore, according to the PTAB, the breadth of zoledronic acid concentration ranges disclosed in the specification was more comprehensive than, and therefore distinguishable from, the more limited concentration ranges disclosed in Wertheim (where the claimed range of “at least 35%” was not supported by disclosure of 25% to 60% range disclosed in priority application). In short, the PTAB determined that a person of ordinary skill in the art, namely, a medical doctor with experience treating CRPS, would have recognized that the “inventor invented what is claimed” and did not overreach in claiming “at least 10% zoledronic acid” in an orally administered dosage form for treating CRPS.

This post was written by Lisa Mueller.