Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant’s election without traverse of Group I (i.e., claims 1-9 directed to a microparticle comprising a degradable polymer and a compound selected from CCL2, IL-4, IL-17 antibody and mixtures or blends thereof) in the reply filed on June 26, 2025, is acknowledged. Additionally, Applicant’s election without traverse of Species A (i.e., a single and specific microparticle as a microparticle comprising PLGA as the degradable polymer and CCL2 as the compound); and Species B (i.e., inflammation in claim 8 as the specific tissue inflammation or disease associated with tissue inflammation) in the reply filed on June 26, 2025, is acknowledged.
Status of Claims
Claims 1-13 were originally filed on June 21, 2022.
The amendment received on March 9, 2026, canceled claims 12-13; amended claims 1 and 8-9; and added new claims 14-19.
Claims 1-11 and 14-19 are currently pending and claims 14-19 are under consideration as claims 10-11 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, and claims 1-9 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on June 26, 2025.
Please note that in light of Applicants’ amendments to claims 1 and 9 such that the elected species of CCL2 as the compound is no longer recited, but is now recited in new claim 14, amended claims 1 and 9 no longer encompass Applicant’s elected species. Thus, claims 1 and 9 and the claims dependent thereof are withdrawn from examination.
Priority
The present application claims status as a 371 (National Stage) of PCT/US2021/014285 filed January 21, 2021, and claims priority under 119(e) to U.S. Provisional Application No. 62/963,632 filed on January 21, 2020.
Response to Arguments
Applicant’s arguments, see Response, filed 3/9/26, with respect to the objections to the drawings have been fully considered and are persuasive. The objection of Figures 6D, 7C, 7D, 8B, 10A, 10B, 11A1, 11A2, 11A3, 11A4, 11B1, 11B2, 11B3, 12B1, 12B2, 12B3, 12B4, 13B1, 13B2, 13B3, 13B4, 14B1, 14B2, 14B3, and 14B4 has been withdrawn.
Applicant’s arguments, see Response, filed 3/9/26, with respect to the objection to the specification have been fully considered and are persuasive. The objection of the specification has been withdrawn.
Applicant’s arguments, see Response, filed 3/9/26, with respect to the claim objection have been fully considered and are persuasive. The objection of claims 1 and 9 has been withdrawn.
Applicant’s arguments, see Response, filed 3/9/26, with respect to the 112(a), scope of enablement, rejection have been fully considered and are persuasive. The rejection of claim 8 as failing the enablement rejection has been withdrawn.
Applicant’s arguments, see Response, filed 3/9/26, with respect to the 102(a)(1) rejection have been fully considered and are persuasive. The rejection of claims 1-4 and 8-9 as being anticipated by Zhuang et al., J. Dental Res. 98:200-208 (first e-published on November 2018) (cited in the IDS received on 6/21/22) has been withdrawn.
New Rejections Necessitated by Amendment
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 14-19 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Independent claim 14 includes a “microparticle comprising a degradable polymer” where the degradable polymer is loaded with the compound and the microparticle is structured to provide a sustained, controlled release of the compound from the degradable polymer and where the controlled release of the compound is absent of a burst effect. Structurally, the microparticle only requires two components; namely, any degradable polymer, and a CCL2 compound. There is no required structure relating to the microparticle exhibiting the claimed functional properties such that the controlled release is absent of a burst effect. As such, there is no core microparticle structure necessary for the microparticle to exhibit a sustained, controlled release of the CCL2 compound such that the controlled release of the compound is absent a burst effect. Similarly, claims 15-17 are directed to where the sustained, controlled release of the compound is a substantially linear rate of release such as a rate that does not vary by more than about 10% or 20% over a selected period of time. As such, there is no core microparticle structure necessary for the microparticle to exhibit this sustained, controlled release rate over a selected period of time. Moreover, claims 18-19 are directed to where the compound is released in an amount from 0.001 to ng per 24-hour period or from 0.01 to 1 ng per 24-hour period. As such, there is no core microparticle structure necessary for the microparticle to exhibit this sustained, controlled release such that the compound is released in such amounts in a 24-hour period. Therefore, the claimed microparticle is required to exhibit specific functional properties without a core structure necessary for the microparticle to exhibit the specifically claimed functional properties.
The written description requirement may be met by provided a representative number of species of the genus and/or in light of the state of the art. With regard to the state of the art, Zhuang et al. discloses microparticles loaded with CCL2 for controlled release (See Zhuang et al., J. Dental Res. 98:200-208 (first e-published on November 2018) (cited in the IDS received on 6/21/22) at abstract). More specifically, Zhuang et al. fabricated rmCCL2-releasing PLGA microparticles with a water-oil-water double-emulsion procedure (See Zhuang, pg. 202, col. 1, 1st paragraph). In Appendix 1, Zhuang et al. teaches that an aqueous solution comprising 28 mcg of rmCCL2 and 15 mM NaCl in 200 µL of 1% (wt/vol) bovine serum albumin solution was added into an oil phase comprising 200 mg of PLGA in 4 mL of dichloromethane followed by 10 seconds of sonication at 25% amplitude, which is the first water-in-oil emulsion step (See Zhuang, Appendix 1; pg. 202, col. 1, 1st paragraph). The second water-in-oil emulsion step was done by homogenizing the sonicated solution in 60 mL of 2% (wt/vol) polyvinyl alcohol for 60 seconds at 3,000 rpm (See Zhuang, Appendix 1). Subsequently, the solution was mixed with 80 mL of 1% polyvinyl alcohol, and stirred on an agitator for 3 hours at 600 rpm, allowing PVA to evaporate along with dichloromethane (See Zhuang, Appendix 1). The microparticles were then collected and washed four times with deionized water, and the final solution was lyophilized for 48 hours (See Zhuang, Appendix 1). Zhuang et al. found that the release profile of CCL2 from these rmCCL2-containing PLGA MPs showed a burst release in the first 72 hours, continued by a slow and steady release phase, then a lag phase of quick release up to 71 days when the particles were completely dissolved (See Zhuang, pg. 203, col. 1, last paragraph; Figure 1E). Thus, Zhuang et al. demonstrates a specific example of microparticle comprising PLGA as a degradable polymer and CCL2 as a compound where the microparticle is produced via a water-oil-water double-emulsion procedure with specific components and amounts of the components where these microparticles exhibit a burst effect.
Furthermore, Jhunjhunwala et al. designed a release vehicle for the steady release of CCL22 (See Jhunjhunwala et al., Adv. Mater. 24:4735-4738 (2012) at pg. 2, 2nd paragraph). Jhunjhunwala et al. teaches that previously developed polymeric-microparticle-based controlled-release systems for proteins (including chemokines) have previously been developed, but the release of hydrophilic proteins from these particles typically follows a triphasic release profile (See Jhunjhunwala, pg. 2, 2nd paragraph). Jhunjhunwala et al. sought to achieve release of CCL22 without any periods of lag in order to produce a corresponding steady gradient of chemokine originating from a point source (See Jhunjhunwala, pg. 2, 2nd paragraph). To this end, Jhunjhunwala et al. teaches that one of the major factors affecting the rate of release is the erosion of a dense polymer matrix into a porous macrostructure that allows for protein egress (See Jhunjhunwala, pg. 2, 2nd paragraph). The timing of this process and, in turn, the period of lag is determined by the type of polymer, its molecular weight (inherent viscosity), and the degree of porosity in the matrix (See Jhunjhunwala, pg. 2, 2nd paragraph) (See also: Fedorchak et al. WO 2018/005780 A1 published on January 4, 2018: teaching several parameters that affect the release rate of an agent are the porosity of a particle, polymer molecular weight (which correlates to degradation rate of the particles), inner occlusion size (which can be controlled independent of surface porosity to program a delayed burst), and concentration and/or composition of encapsulated agents (See ‘780, [0042], [00105])). Jhunjhunwala et al. added contiguous pores to the microparticles during fabrication, which would pre-establish pathways for diffusive protein egress and should bypass the need for erosion as a requisite for release (See Jhunjhunwala, pg. 2, 2nd paragraph). In particular, Jhunjhunwala et al. used PLGA as the polymer with a specific inherent viscosity of 0.16-0.24 dl/g in 0.1% chloroform in order to achieve release within a 3-8 week period, and modified the surface porosity using an osmotic gradient between the inner aqueous emulsion and the outer bulk aqueous phase (See Jhunjhunwala, pg. 2, 2nd paragraph). Jhunjhunwala et al. found that porous microparticles prepared using a specific osmotic gradient (corresponding to 15 x 10-3 M NaCl in inner aqueous emulsion) when compared to unmodified degradable particles did not display the standard lag phase that would be expected as depicted in Figure 1b (See Jhunjhunwala, pg. 2, 2nd paragraph). Plus, as an additional design parameter, the particles were made to be large enough to avoid uptake by phagocytic cells and to prohibit their movement across vascular endothelium (See Jhunjhunwala, pg. 2, 2nd paragraph). However, it is not readily apparent from Figure 1b if the release rate does not vary by more than 10% or 20% over a selected period of time; or the amount of compound released in a 24-hour period. Although the art suggests certain parameters to consider when fabricating microparticles that would result in a sustained, controlled release of a compound, the specific methods of producing the microparticles and the specific components in specific amounts are critical in achieving microparticles that exhibit the instantly claimed functional properties. Thus, the claims are directed to microparticles with certain functions but no correlated structure associated with that function. Without such structure, the specification does not convey possession of the breadth of the claimed genus.
Alternatively, the written description requirement may be met by provided a representative number of species of the genus. In this, the specification only provides a microparticle species that exhibits an initial burst effect, but no microparticle species meeting the claimed functional limitations. Example 1 teaches that PLGA MPs loaded with anti-IL17A antibody were fabricated using a standard water-oil-water double emulsion procedure (See instant, [0076]). A 200 µl aqueous solution comprising anti-mouse IL-17A antibody in a concentration of 1 mg/ml in PBS was added to an oil phase comprising 200 mg PLGA dissolved in 4 ml dichloromethane as an organic solvent (See instant, [0076]-[0077]). The resultant mixture was sonicated for 10s (first emulsion of water-in-oil) then added to 60 ml of 2% poly (vinyl alcohol) (PVA) solution (MW = 25,000 gmol/l) and then homogenized for 1 minute at 3000 rpm (See instant, [0077]). The homogenized solution (second emulsion) was then added to 80 ml of 1% PVA and stirred for 3 hours to allow for evaporation of dichloromethane (See instant, [0077]). Next, the MPs in suspension were centrifuged and washed 4 times in deionized water, resuspended in deionized water, flash frozen in liquid nitrogen and lyophilized for 72 hours (See instant, [0077]). The release profile of these MPs shows an initial burst release of 0.7 ng/ml followed by a relatively steady release of additional 0.1 ng/ml per day, continuing until day 11 (See instant, [0093]). An increase in the anti-IL17A release rate took place starting day 12 with 0.2 ng/ml being released until day 14 as depicted in Figure 1A (See instant, [0093]). Total loading of anti-IL17A in PLGA was 20% of the amount initially used in the fabrication (See instant, [0093]). As such, the MPs taught in the specification appear to exhibit two separate burst effects. Thus, the MPs taught in the specification do not constitute a representative number of species that fall within the claimed genus that would allow an ordinary skilled artisan to extend the functional properties to the scope of the claimed genus. Therefore, the specification is not sufficient for the skilled artisan to envisage which MP structures preserve the claimed functions as there is no indication of a core structure necessary for the MPs to exhibit such claimed functions.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, what is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116). As discussed above, the skilled artisan cannot envision the detailed chemical structure of the encompassed genus of polypeptides which preserve the required function, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483. In Fiddes, claims directed to mammalian FGF’s were found to be unpatentable due to lack of written description for that broad class. The specification provided only the bovine sequence. Therefore, claims 14-19 do not meet the written description requirement.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
103 - KSR Examples of 'Rationales' Supporting a Conclusion of Obviousness(Consistent with the "Functional Approach" of Graham)
Further regarding 35 USC 103(a) rejections, the Supreme Court in KSR International Co. v. Teleflex Inc., 550 U.S. 398, 127 S. Ct. 1727, 82 USPQ2d 1385, 1395-97 (2007) (KSR) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper "functional approach" to the determination of obviousness as laid down in Graham. The key to supporting any rejection under 35 U.S.C. 103 is the clear articulation of the reason(s) why the claimed invention would have been obvious. The Supreme Court in KSR noted that the analysis supporting a rejection under 35 U.S.C. 103 should be made explicit.
Exemplary rationales that may support a conclusion of obviousness include:
(A) Combining prior art elements according to known methods to yield predictable results;
(B) Simple substitution of one known element for another to obtain predictable results;
(C) Use of known technique to improve similar devices (methods, or products) in the same way;
(D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results;
(E) "Obvious to try" - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;
(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art;
(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Note that the list of rationales provided is not intended to be an all-inclusive list. Other rationales to support a conclusion of obviousness may be relied upon by Office personnel.
Also, a reference is good not only for what it teaches by direct anticipation but also for what one of ordinary skill in the art might reasonably infer from the teachings. (In re Opprecht 12 USPQ 2d 1235, 1236 (Fed Cir. 1989); In re Bode 193 USPQ 12 (CCPA) 1976).
Claims 14-19 are rejected under 35 U.S.C. 103 as being unpatentable over Fedorchak et al. WO 2018/005780 A1 published on January 4, 2018, alone or as evidenced by Watson et al., Intl. J. Biochem. Cell Biol. 41:729-732 (2009).
For claim 14, with respect to a microparticle comprising: a degradable polymer such as PLGA and a CCL2 compound where the degradable polymer is loaded with the compound:
‘780 teaches a composition comprising a first particle comprising conditioned medium from a cell culture within the particle and having a first release profile of the conditioned medium (See ‘780, [0006]), and a controlled release pharmaceutical device comprising a polymer in which the conditioned media is distributed or otherwise contained (See ‘780, [0010], [0057]). A specific species of particle is a PLGA particle that is fabricated using three different configurations, i.e., non-porous, porous and burst (See ‘780, [0016]). ‘780 teaches that PLGA is a species of bioerodible polymer, which is defined as a polymer that once is implanted and placed in contact with bodily fluids and/or tissues will degrade either partially or completely through chemical, biochemical and/or enzymatic processes (See ‘780, [0027]-[0029]). As such, ‘780 teaches utilizing PLGA as a degradable polymer. The conditioned medium can contain mesenchymal stem cells (MSCs), and other active agents where these other active agents can also be incorporated into the particles and/or controlled-release devices (See ‘780, [0035], [0063]). The active agents can be growth factors, cytokines, chemoattractants and/or inflammation regulators, which are used to supplement the conditioned medium to tailor the cellular response, deposition, growth and other aspects of the tissue remodeling process (See ‘780, [0063]). ‘780 refers to active agents that were previously discussed, i.e., “as indicated above”, thereby encompassing the growth factors such as MCP-1 that have been encapsulated by microspheres (See ‘780, [0063]) thereby constituting where the polymer is loaded with the compound as recited in instant claim 14. More specifically, ‘780 teaches that microsphere particles have been utilized to deliver distinct factors (See ‘780, [0041]). Microspheres are commonly used as a delivery vehicle and offer the ability to fine tune their properties to achieve a variety of sizes and timed release rates (See ‘780, [0041]). ‘780 also teaches that microspheres have been extensively utilized to release several compounds such as growth factors (e.g., VEGF, FGF, PDGF, MCP-1, TGF-beta, EGF, BMP-2, BMP-7, IGF-1, drugs, peptides and siRNAs) (See ‘780, [0041]). As evidenced by Watson et al., CCL2 is also known as MCP-1 (See Watson, pg. 729m col. 1, 1st paragraph). As such, ‘780 teaches CCL2 as a growth factor known to be encapsulated in a microsphere.
Furthermore, ‘780 teaches a formulation of particles as a system for the controllable release of multiple bioactive factors produced by specific cell types such as MSCs (See ‘780, [0044]). The factors that can be produced by MSCs include MCP-1 (See ‘780, [0089]). In one aspect, the formulation comprises particles of any suitable degradable or non-degradable material, e.g., PLGA, that are porous or non-porous, and conditioned media dispersed through the particle (See ‘780, [0044]). In another aspect, ‘780 teaches a product comprising a delivery matrix comprising the conditioned media for release of the conditioned media in a controlled manner (See ‘780, [0044]). The matrix can have any suitable shape such as a particle, and can be polymeric, e.g., as a porous and/or biodegradable matrix, where the polymer can be PLGA (See ‘780, [0044], [0046]). The particles can be of any useful size, typically ranging from nanometer to micrometer scale (See ‘780, [0046]-[0047]) thereby constituting a microparticle as recited in instant claim 14. Thus, when considering the teachings of ‘780 as a whole, ‘780 suggests a controlled release pharmaceutical device or a formulation comprising a porous, non-porous or burst matrix composed of microparticles comprising a degradable polymer such as PLGA, a conditioned media containing MSCs, and other active agents such as MCP-1, where the microparticles are loaded with the conditioned media and other active agent(s) as further articulated below.
For claim 14, with respect to where the microparticle is structured to provide a sustained, controlled release of the compound from the degradable polymer and where the controlled release of the compound is absent of a burst effect as recited in instant claim 14:
As discussed supra, ‘780 teaches a composition comprising a first particle comprising conditioned medium from a cell culture within the particle and having a first release profile of the conditioned medium (See ‘780, [0006]), and a controlled release pharmaceutical device comprising a polymer in which the conditioned media is distributed or otherwise contained (See ‘780, [0010], [0057]). A specific species of particle is a PLGA particle that is fabricated using three different configurations, i.e., non-porous, porous and burst (See ‘780, [0016]). Moreover, in Example 1, ‘780 examines the release rate of conditioned media where MSC conditioned media is encapsulated within particles and the particles are allowed to release their cargo in ultrapure water in an incubator at 37°C (See ‘780, [0087]). As depicted in Figure 4, ‘780 developed distinct release profiles utilizing MSC-conditioned-media-loaded particles fabricated with non-porous and increasingly porous configurations using a double emulsion procedure (See ‘780, [0088]). Release is tunable by an order of magnitude as well as by as little as 2-fold by simply varying the porosity of the particles (See ‘780, [0088]). It is also possible to tune the ratio of the amount delivered within the first two days compared to the amount delivered over the first week of release (See ‘780, [0088]). Although ‘780 teaches that the most appealing release is the “burst” configuration, ‘780 does not teach that the porous and non-porous configurations should absolutely not be used or would not be useful for any purpose; especially since Figure 4 demonstrates that the non-porous configuration provided a sustained, controlled release of the MSC conditioned media from the degradable PLGA and the controlled release is absent of a burst effect (See ‘780, Figure 4). Furthermore, ‘780 teaches that the primary parameter that is varied to achieve temporally distinct burst releases is porosity, which preliminary studies suggest allows for a wide range of release behavior within the appropriate levels (See ‘780, [0042], [00105]). Other influencing factors such as polymer molecular weight (which correlates to degradation rate of the particles) and inner occlusion size (which can be controlled independent of surface porosity to program a delayed burst), also is accounted for when generating these well-defined families (See ‘780, [0042], [00105]). ‘780 also teaches that concentration and/or composition of encapsulated factors can be parameter to consider when determining a desired release rate of an agent (See ‘780, [0042]). As such, ‘780 teaches critical parameters to adjust as necessary in order to achieve the desired release rate. Thus, ‘780 teaches where the microparticle is structured to provide a sustained, controlled release of a compound from the degradable polymer and where the controlled release of the compound is absent a burst effect as recited in instant claim 14.
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant application to fabricate a microparticle comprising PLGA as a degradable polymer, MSC conditioned media, and MCP-1 as another active agent where the MSC conditioned media and MCP-1 is encapsulated by PLGA and the microparticle is structured as a non-porous matrix in order to provide a sustained, controlled release of the MSC conditioned media and MCP-1 from PLGA such that the controlled release is absent of a burst effect. One of ordinary skill in the art at the time the invention was made would have been motivated to do so because active agents such as growth factors including MCP-1 were known to be delivered in a sustained, controlled release manner in vivo or in vitro via encapsulation by microparticles comprising a delivery matrix of a degradable polymer such as PLGA where the matrix is structured as a non-porous, porous or burst matrix; and because a delivery matrix composed of a degradable polymer such as PLGA that is structured in a non-porous configuration was known to exhibit a controlled release rate that is absent of a burst effect as taught by ‘780. One of ordinary skill in the art at the time the invention was made would have had a reasonable expectation of success given that the delivery matrix of ‘780 was composed of a microparticles comprising a degradable polymer that encapsulates MSC conditioned media and one or more active agents where the microparticles are fabricated for a sustained, controlled release of the MSC conditioned media and one or more active agents. Therefore, substituting PLGA as the degradable polymer and MCP-1 as the one or more active agents such that the PLGA delivery matrix is in a non-porous configuration would support the fabrication of microparticles structured to provide a sustained, controlled release that is absent of a burst effect by constituting the simple substitution of one known element for another to obtain predictable results and/or some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention pursuant to KSR.
Additionally and/or alternatively, it is noted that the instantly claimed invention is directed to a product, i.e., microparticles. The required structure recited in claim 14 is that the particles are to be micro in size, and comprise any degradable polymer and a CCL2 compound, and where the degradable polymer is loaded with the CCL2 compound. Although claim 14 recites that the microparticle is structured in order to provide a sustained, controlled release of the CCL2 compound from the degradable polymer, there is no specific structure recited. As such, the structural requirements of claim 14 are limited to the aforementioned structures whereas the microparticle structured to provide a sustained, controlled release of the compound from the degradable polymer in a manner that is absent of a burst effect constitutes functional properties of the claimed microparticles. Pursuant to MPEP 2112.01(II), “[p]roducts of identical chemical composition cannot have mutually exclusive properties.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id. Thus, in the instant case, since ‘780 suggests the required structure of the claimed particles, the ‘780 suggested particles would necessarily exhibit the claimed functional properties. Pursuant to MPEP 2112(I), the claiming of a new use, new function or unknown property which is necessarily present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). The discovery of a previously unappreciated property of a prior art composition, or a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer. Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999).
For claims 15-19, with respect to where the sustained, controlled release of the compound is a substantially linear rate of release as recited in instant claim 15; with respect to where the compound is released at a rate that does not vary by more than about 20% over a selected period of time as recited in instant claim 16; with respect to where the compound is released at a rate that does not vary by more than about 10% over a selected period of time as recited in instant claim 17; with respect to where the compound is released in an amount from 0.001 to 2 ng per 24-hour period as recited in instant claim 18; and with respect to where the compound is released in an amount from 0.01 to 1 ng per 24-hour period as recited in instant claim 19:
‘780 defines “slow”, “delayed”, “extended”, and “modified”-release as meaning that the constituents of the conditioned media are released from the matrix over time and not immediately as a bolus, for example, over 1-24 hours or over 1-21 days, or even over weeks or months (See ‘780, [0045]). Moreover, as discussed supra, Figure 4 demonstrates that the non-porous configuration provided a sustained, controlled release of the MSC conditioned media from the degradable PLGA and the controlled release is absent of a burst effect (See ‘780, Figure 4).
However, although ‘780 does not expressly teach that the sustained, controlled release of the MSC conditioned media is a substantially linear rate of release (note: defined in the instant specification as meaning that the agent is released at a rate that does not vary by more than about 20% over the desired period of time and, more usually, by not more than about 10% (See instant, [0056])) where the release rate does not vary by more than about 10% or 20% over a selected period of time, and where the compound is released in an amount from 0.001 to 2 ng or 0.01 to 1 ng per 24-hour period, these limitations constitute functional properties of the claimed microparticles. Pursuant to MPEP 2112(I), the claiming of a new use, new function or unknown property which is necessarily present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). The discovery of a previously unappreciated property of a prior art composition, or a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer. Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999).
Additionally and/or alternatively, for claims 16-19, pursuant to MPEP 2111.04(I), [c]laim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed, or by claim language that does not limit a claim to a particular structure. However, examples of claim language, although not exhaustive, that may raise a question as to the limiting effect of the language in a claim are:
(A) "adapted to" or "adapted for" clauses;
(B) "wherein" clauses; and
(C) "whereby" clauses.
The court has found that the determination of whether clauses such as “wherein” and “whereby" is a limitation in a claim is dependent on the specific facts of the case. If the “wherein" or “whereby” clause limits a process claim where the clause gives meaning and purpose to the manipulative steps, it should be given patentable weight. Griffin v. Bertina, 285 F.3d 1029, 1034, 62 USPQ2d 1431 (Fed. Cir. 2002). However, the court also found (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)) that a “‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’” In the instant case, the claimed compound is intended to be released from the degradable polymer at a rate that does not vary by more than about 10% or 20% over a selected period of time, or intended to be released in an amount from 0.001 to 2 ng or 0.01 to 1 ng per 24-hour period constitutes the intended use of the claimed microparticle, and thus, there is no structure imparted by such uses other than excluding prior art with expressed teaching of microparticles exhibiting a burst effect which would not result in the release rates or released amounts. Since ‘780 renders obvious the claimed microparticle structure, as discussed supra, the intended use limitations recited in the “wherein” clauses are met. Therefore, the teachings of ‘780 satisfy the claim limitations as recited in instant claims 15-19.
Thus, the invention as a whole is prima facie obvious over the references, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant’s arguments with respect to claims 14-19 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/THEA D' AMBROSIO/Primary Examiner, Art Unit 1654
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