In Ex parte Freeman (USSN 16/270,259; TC 1600; Appeal 2023-000512, the underlying application being referred to herein as the "Freeman application"), a finding of obviousness and obviousness-type double patenting (ODP) was reversed on May 24, 2024. Freeman's application was examined by Devang Thakor initially, but the case was taken over by another primary examiner, Nicole Babson, whose position was supported by Supervisor Patent Examiners, David Blanchard and Bethany Barham.
Claim 1 of the Freeman application, after preliminary amendment, claimed
[a] composition comprising:
a porous particulate material comprising silicon dioxide, the porous particulate material having been heated in an oxidizing environment at a temperature at or above 800°C; and
a drug or biologically active material within the porous particulate material.
Claim 1 of then copending US Appl. Ser. No. 15/804,856 (as of February 8, 2022, US 11,241,380), over which the claims of the Freeman application were rejected for obviousness-type double patenting (ODP), recited
[a] drug delivery device for use in the controlled delivery of a particular drug or drugs to a particular location of the eye, the device comprising:
micron sized porous silicon dioxide particles having pores configured and dimensioned to at least partially receive at least one drug therein; and
the at least one drug;
wherein the at least one drug is an antiangiogenic drug selected from the group consisting of angiostatic steroids, metalloproteinase inhibitors, and vascular endothelial growth factor binding drugs;
wherein the particles are prepared by etching a crystal silicon substrate, fracturing the substrate into micron-sized particles, and oxidizing the micron-sized particles in air;
wherein the pores are configured and dimensioned to have a pore size ranging from approximately 1 nanometer to 1 μm; and
wherein the particles are suitable to be delivered into or onto the eye.
There were 2 further independent claims in US 11,241,380 with similar salient feature, but none of the 9 claims of US 11,241,380 recited anything on temperature or the structural feature of silica imparted by such a 800°C treatment of silica, besides potentially the pore size range.
The description of the Freeman application, in ¶ [0005], describes that
minimally invasive controlled drug delivery systems and methods for use in delivery of a particular drug or drugs to the eye that include porous film or porous film particles having pores configured and dimensioned to at least partially receive at least one drug therein. Embodiments include devices and methods for treating intraocular diseases where porous film particles impregnated with a particular drug are sized and configured to permit intraocular injection of the loaded porous film particles. Other embodiments include devices and methods for treating extraocular diseases, where one of a porous film, biodegradable polymer replica, porous SiO2-polymer composite, or porous Si-polymer composite impregnated with a particular drug is configured to contact a portion of the eye, such as the ocular surface or retrobulbar surface, and controllably release the drug for surface delivery of the drug. Advantageously, release of the drug is also monitorable such that the amount of drug remaining in the porous substrate can be accurately quantified.
As noted by the Patent Trial and Appeals Board (PTAB), the Freeman application describes that "methods for producing porous SiO2 particles by oxidation of porous Si at 800°C. Particles manufactured in this manner are more hydrophilic than the previous oxidized ones which were processed at 220°C," in ¶ [0163] of the description.
The claims of the Freeman application were rejected non-finally as obvious on September 29, 2020, over a combination of references, i.e., WO 2006/050221 A1 (Freeman, with encompassing inventorship relative to the Freeman application), Appl. Phys. Lett. 2005, 86, 041501 (Pap); and N. Engl. J. Med. 2006, 355, 1419-1431 (Rosenfeld). The examiner's theory behind the obviousness position was that, while failing to address the temperature issue, Freeman describes
minimally invasive controlled drug delivery systems and methods for use in delivery of a particular drug or drugs to the eye that include porous film or porous film particles having pores configured and dimensioned to at least partially receive at least one drug therein. Embodiments include devices and methods for treating intraocular diseases where porous film particles impregnated with a particular drug are sized and configured to permit intraocular injection of the loaded porous film particles. Other embodiments include devices and methods for treating extraocular diseases, where one of a porous film, biodegradable polymer replica or porous Si-polymer composite impregnated with a particular drug is configured to contact a portion of the eye, such as the ocular surface or retrobulbar surface, and controllably release the drug for surface delivery of the drug. Advantageously, release of the drug is also monitorable such that the amount of drug remaining in the porous substrate can be accurately quantified.
The examiner admitted that Freeman only described an oxidation temperature of 300°C, but relied upon Pap's disclosure that the extent of the oxidation depends upon temperature, and that an oxidation temperature of 200°C yielded 10% oxidation, while an oxidation temperature of 800°C yielded 50% oxidation. Pap was argued to describe temperatures of 600 or 800°C, so the examiner argued that "one of ordinary skill in the art would have been motivated to use a higher oxidation temperature, i.e., 800 °C, to increase the extent of oxidation and increase the stability of the silicon material of Freeman." Rosenfeld was only relied upon for its description of ranibizumab.
The applicant responded without amending the claims and arguing, with the support of a declaration under 37 CFR § 1.132 by UCSD professor and co-inventor, Michael Sailor (Sailor Declaration), that (emphasis original)
Applicant disagrees that a prima facie case for obviousness of the claimed compositions has been made. Specifically, Applicant disputes that one of ordinary skill in the art at the time of the invention would have been motivated by the teaching of Freeman and/or Pap to increase Freeman's temperature of oxidation temperature to 800°C or above in order to achieve the claimed compositions. In particular, applicant notes that Pap is not directly relevant to the thermal oxidation of the porous silicon particulate matter of the instant claims, since it relates to the thermal oxidation of porous silicon layers. As noted at paragraph 8 of the accompanying Declaration under 37 C.F.R. § 1.132 of co-inventor Michael Sailor, the conversion of elemental Si to SiO2 by thermal oxidation in air involves three processes, each of which has a unique temperature dependence: 1) reaction of oxygen at the Si surface to form the oxide; 2) diffusion of oxygen through the growing SiO2 layer to the Si/SiO2 interface; and 3) thermal annealing and viscous flow of the oxide. These processes would be understood by those of skill in the art to depend further on the thickness and shape of the porous silicon starting material, in particular whether or not the porous silicon was on the surface of a two-dimensional silicon layer (as in Pap) or on the surface of particulate material prepared by the fracture of such silicon layers (as in Freeman).
Even if Pap's thermal oxidation of porous silicon layers was considered relevant to the thermal oxidation of Freeman's porous silicon particles, Pap discloses structural changes in porous silicon that occur during oxidation at 800°C that would discourage one of ordinary skill in the art from applying the higher temperatures to Freeman's particles. Specifically, Pap teaches that the use of a higher oxidation temperature, although causing more Si to be transformed to SiO2, also causes "loss of crystalline structure", thus "resulting in a partly amorphous form". See Pap, Figure 2. One of ordinary skill in the art, with Freeman in hand, would not have considered increasing the oxidation temperatures of Freeman above 600°C in view of the structural transformations observed by Pap at 800°C. Those structural transformations are clearly highlighted by the abrupt drop in relative lattice deformation shown between 873 K (i.e., 600°C) and 1073 K (i.e., 800°C) in Figure 4 of Pap.
Pap additionally highlights the importance of lattice deformation and thermomechanical stress in porous silicon layers having different extents of oxidation, factors that have far different impacts on the much smaller porous silicon particles of Freeman and of the instant disclosure, with their significantly larger surface area to volume ratios compared to porous silicon layers. Importantly, the thermomechanical stress referred to by Pap arises in part because the films of Pap are still in contact with the crystalline silicon substrate. Due to its lack of pores, the crystalline silicon substrate does not oxidize as does the porous layer. Because it does not oxidize under the conditions of Pap, the crystalline silicon substrate retains its original dimensions. The porous layer, on the other hand, undergoes substantial changes in physical dimensions due to the conversion of silicon to silicon oxide, and this leads to the aforementioned thermomechanical stress. Because the particulate material of the instant application is not attached to a silicon substrate, it is not subjected to the same stresses considered so important by Pap.
The applicant argued that it would not have been reasonably expected that Pap's "high-temperature thermal oxidation of porous silicon layers to achieve the high-temperature oxidized porous silicon particulate material as currently claimed." Thus, the applicant argued that there was a technical reason guiding Pap's oxidation treatment which would not have been present for Freeman, but also provided declaratory evidence in support of the patentability of the Freeman application. The attorney remarks indicated that
Applicant provides the above-mentioned declaration from inventor Michael Sailor, together with a scientific publication from his laboratory at the time of the invention (Cheng et al. (2008) Br. J. Ophthalmol. 92:705-11 ("Cheng")) that compares the intravitreal properties of porous silicon-containing particles oxidized at a temperature of 800°C to those oxidized for much longer times at 220°C.
The Sailor Declaration indicated in statement #8 that "[p]orous silicon that is heated in an oxidizing environment at a temperature at or above 800°C differs structurally and functionally in significant ways from porous silicon that has been oxidized at lower temperatures." Statement #8 contained language reproduced in the attorney arguments of the response to the non-final rejection and cited several academic publications supporting the "three interrelated process" traversal on Si oxidation, of which eight were included as exhibits to the Sailor Declaration. Only one of the exhibits included Sailor as a co-author, i.e., the Cheng reference. The Sailor Declaration indicated in statement #9 that silica heated to 800°C or above had "unique and unexpected properties," pointing to ¶¶ [0073], [0163], and [0164] of the Freeman application. The Sailor Declaration indicated that the inventors had undertaken temperature-based experiments in the Cheng reference and determined surprisingly that "significantly longer residence times of the high-temperature oxidized particles compared to particles prepared using low-temperature oxidation, and at the much lower surface degradation observed with the high-temperature oxidized particles."
The Sailor Declaration's statement #14 also argued that a person of ordinary skill in the art at the time of the invention "would not have looked to Pap" to increase Freeman's oxidation temperature of porous Si particles,
because, even in view of the teaching of Freeman and Pap, that person would not have been aware of the fundamental differences in structure and function of porous silicon oxidized at a high temperature and, most importantly, would not have understood how those differences in structure and function would affect the adsorption of drugs to the particles, the long-term stability of those particles in animal vitreous fluid, and the lack of toxicity of the particles in animals.
The Sailor Declaration acknowledged that Pap discloses higher-temperature thermal oxidation of porous silicon, but argued that this "in no way predicts that particles oxidized at the higher temperatures would have such [unexpected results]."
After the first response and filing of the Sailor Declaration, the Freeman application was then finally rejected for essentially the same reasons. The (new) examiner made the somewhat common and formulaic argument — divorced from the statements in the declaration — that the Sailor Declaration was insufficient to overcome the rejections of record because the Sailor Declaration allegedly was based on "declaration on declaring that a difference in structure and function exists when a porous silicon is heated in an oxidizing environment at the claimed temperature (at or above 800°C) rather than the temperature disclosed by Freeman." The examiner argued that her hindsight combination of three references negated the strength of the statements of the Sailor Declaration. The examiner argued that the unexpected results needed to be based on the closest prior art (which the examiner did not identify) and rotely argued based on MPEP § 2145(II), encouraging such rote regurgitation, that "Freeman and Pap render obvious the claimed structure. Properties derived from an obvious structure do not render non-obvious an otherwise obvious structure, even if the properties were not recognized by the prior art." The problem with the examiner and her supervisors' understanding of this MPEP language cited to refute the showing of unexpectedly superior results was that MPEP § 2145(II) refers to scenarios in which the property in question is essentially inherent. The examiner further insisted that her prima facie finding was essentially sufficient to dismiss the rebuttal evidence, arguing that
Freeman [the declarant's own invention] clearly and explicitly teaches that oxidation of the silicon-containing material increases its stability and thus increases is residence time (page 7, line 10; page 13, lines 3-6), i.e., that oxidization is associated with stability. This provides clear motivation to increase the extent of oxidation. Pap clearly teaches that the extent of oxidation increases as the oxidation temperature increases (Figure 2) and thus provides the means to increase the oxidation of the particles of Freeman. Applicant's declaration does not address these teachings, particularly the explicit teaching of Freeman that is used as the actual basis for rejection. Applicant's declaration does not explain why even after reading Freeman and Pap including the text cited above, one of ordinary skill would still not have reasonably expected that increasing the oxidation temperature would increase the extent of oxidation and thus provide the benefit clearly described by Freeman.
The applicant directly appealed the final rejection, repeating several of the arguments already of record and clarifying to the examining corps that the examiner "completely ignored the unexpectedly advantageous properties of the claimed compositions, arguing that a finding of unexpected results must be based on a comparison with the closest prior art," pointing to "Professor Sailor's description of the comparison of high-temperature oxidized and low-temperature oxidized particles at paragraph 10 of the June 21, 2015 Declaration," and Sailor's statement regarding the difference between Freeman's heating for 300°C for 2 hours and the heating at 220°C for 24 hours in the Cheng reference relied on in the Sailor Declaration, that "[d]espite the minor difference in preparation conditions, ... it is my opinion that the low-temperature particles of Cheng have substantially similar properties to the particles disclosed in Freeman for purposes of comparison." The Examiner's Answer did not address this evidence from the Sailor Declaration, instead repeating only that the comparison was not to the same closest art (ostensibly 300°C experiments in Freeman) and that "Freeman and Pap render obvious the claimed structure," and that "[p]roperties derived from an obvious structure do not render nonobvious an otherwise obvious structure."
The PTAB summarized the issues on appeal to be
(i) Does a preponderance of the evidence of record support the Examiner's conclusion that it would have been obvious to increase the oxidation temperature of Freeman to an 800°C oxidation temperature as performed by Pap?
(ii) If so, has Appellant provided evidence of unexpected results that, when balanced with the prima facie case, supports a finding of non-obviousness?
The PTAB indicated, in the view of the drafting Administrative Patent Judge (APJ), Jeffrey Fredman, that the examiner "provided strong evidence that supports a finding of prima facie obviousness" for the reasons set forth by the examiner, but indicated that the PTAB "need not address Appellant's prima facie case arguments because we agree with Appellant that the evidence in the Sailor Declaration and Specification demonstrate an unexpected result." Citing the holding from In re Soni, 54 F.3d 746, 751 (Fed. Cir. 1995), that "when an applicant demonstrates substantially improved results, as ... here, and states that the results were unexpected, this should suffice to establish unexpected results in the absence of evidence to the contrary," the PTAB opined that "there is no evidence of record that increasing the oxidation of the silicon dioxide particles by heating to 800°C would have been expected to more than double particle residence time in the vitreous fluid of the eye."
Accordingly, without even specifically addressing the examiner's arguments on "closest prior art," the PTAB reversed the examiner and her SPEs' position on the persuasiveness of the evidence of unexpected results.
Applicants may glean several important lessons from the process in Ex parte Freeman.
Firstly, it is wise to file strong and detailed declaratory evidence as soon as possible in prosecution, as long as applicants know the field of the invention well and have a good sense of potential prior art. If the applicant does not expect to amend the claims, and particularly if the applicant does not expect a further combination of prior art to be applied against the claims, it is wise to invest considerably in an early declaration, preferably with experimental data in the chemical arts, which are typically the strongest evidence of non-obviousness.
Secondly, in response to a rejection, arguments against prima facie obviousness, either in a declaration under 37 CFR § 1.132 or in attorney remarks, should not focus on whether the results would have been predictable or reasonably expected, as was done in the Sailor Declaration (statement #14) and as is commonly done in traversing the prima facie obviousness position, as these arguments pertain to unexpected results, which are a rebuttal of an established prima facie obviousness position. Instead, the arguments regarding unexpectedly superior results need to focus on commensurateness, the quality of the comparison to the asserted prior art — i.e., useful data may be closer than the prior art or directly against the closest prior art, and the generalizability of the results to the claims. Declarations under 37 CFR § 1.132 are more persuasive than attorney argument in remarks of office action responses, but are still subject to a degree of examiner or APJ subjectivity in evaluating persuasiveness. Experimental data and third-party technical references are respectively the first and second forms of evidence. Particularly experimental data is more likely than other forms of persuasive argument to—as here—incentivize an APJ to reconsider the deference ordinarily afforded examiners based on subject-matter expertise.
Thirdly, the logic used by researchers and inventors is not the same as the logic used by patent examiners for several reasons, e.g., researchers focus on their specific technology and may not appreciate the scope of their claim, researchers know what art is actually considered by inventors while examiners know what search machines indicate was available in theory to inventors, USPTO examiners do not need to support their scientific hypotheses with evidence and generally argue in conclusory statements which generally go unchallenged — or may have even been trained into the examiners by supervisors — throughout the examining corps, etc. The applicant here argued that a person of skill in the art, i.e., any of the inventors (including Sailor), would not have "looked to Pap to increase Freeman's temperature," but did not explain in detail the risks that may have been known or feared by Prof. Sailor in carrying out the modification. The risks and unpredictability of a modification proposed by an examiner are the main basis of traversing the prima facie obviousness of the claims, which may offer a means of avoiding the "claim commensurateness" issues that arise when relying on rebuttal arguments with unexpectedly superior results. Therefore, inventors should be educated about the approach of USPTO examiners to combining references, and efforts should be made to elicit as much technical information as possible on the risks of the modification of the prior art proposed by the examiner to the primary reference.
Fourthly, many USPTO examiners, based either on training or a lack thereof, believe that strong obviousness positions can be created out of their hypotheses underpinning prima facie obviousness, supplemented by inherency or (as here) "latent properties," which many examiners misunderstand to be "anything that arises out of my hypothesized combination of the art." In fact, the Federal Circuit has frequently cautioned against inherency positions based upon obviousness, e.g., in Par Pharmaceutical v. TWi Pharmaceuticals, Inc., 773 F.3d 1186, 1195-1196 (Fed. Cir. 2014), Honeywell Int'l v. Mexichem Amanco Holding, 865 F.3d 1348 1354 (Fed. Cir. 2017), etc., and MPEP § 2112 continues to properly guide examiners that "[i]n relying upon the theory of inherency, the examiner must provide a basis in fact and/or technical reasoning to reasonably support the determination that the allegedly inherent characteristic necessarily flows from the teachings of the applied prior art," citing to Ex parte Levy, 17 USPQ.2d 1461, 1464 (Bd. Pat. App. & Inter. 1990) (emphasis in original). See also In re Rijckaert, 9 F.3d 1531, 1534 (Fed. Cir. 1993); In re Oelrich, 666 F.2d 578, 581-82 (CCPA 1981); Hansgirg v. Kemmer, 102 F.2d 212, 214 (CCPA 1939), itself citing Parker v. Ballantine, 101 F.2d 220 (CCPA 1939); In re Ball, 81 F.2d 242 (CCPA 1936); and Brand v. Thomas, 96 F.2d 301 (CCPA 1938).
Finally, USPTO examiners vary in "difficulty," generally based on a mixture of personality, research experience, and seniority. Examiner Babson is characterized as "very hard," i.e., in the 88th Difficulty Percentile, in the USPTO analytical website "Patent Bots." https://www.patentbots.com/stats/examiner/1619-BABSON-NICOLE-P . With difficult examiners, it is generally wise, early on, to put the claims into a condition the applicant feels is the most likely to succeed on appeal, and interview cases early to verify if the examiner is willing to allow any claim scope, then to appeal the case early, as was done in Ex parte Freeman. In Ex parte Freeman, the opinion of a renowned research professor and member of the American Association for the Advancement of Science, with decades of actual research experience and hundreds of publications, was pitted against the opinion of several USPTO examiners and APJs—essentially career bureaucrats. While such credentials are not in and of themselves persuasive, and may even indicate skill above that which is "ordinary" in the art, fortunately for the inventors in this case, the PTAB was persuaded by his opinion on the data.
The content of this article is intended to provide a general guide to the subject matter. Specialist advice should be sought about your specific circumstances.