DETAILED ACTION
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 .
Claims 1-20 are pending, all of which have been considered on the merits.
Priority
Acknowledgement is made of Applicants’’ claim for priority under 35 USC 121 as a divisional of prior-filed US application 16/308889 (filed 12/11/2018, now USP 11684574), which is a national stage entry under 35 USC 371 of PCT/US2017/039973 (filed 6/29/2017), which claims benefit of US Provisional application 62/356754 (filed 6/30/2016).
However, the instant application is an improper divisional, and thus will not get the benefit of the ‘121 shield’ over the parent patent 11684574. A divisional application may be filed to claims which are patentably distinct from the claims examined in the parent application. In the instant case, the claims presented for exam are indistinct from those examined in the parent application. Specifically, current claim 1 is identical in scope to claim 1 presented and examined in the parent application. (In the prosecution of the parent application the restriction requirement was withdrawn in its entirety in the office action mailed 7/29/2022.)
Applicants are required to correct the priority claim of the instant application by filing a new ADS, wherein under “domestic priority” the word “divisional” is lined through and the word “continuation” is written in and underlined.
Claim Interpretation
For clarity of record, the broadest reasonable interpretation of the claims is set forth. Use of identifying letters and numerettes are added by Examiner for use in this office action only. (Claims not specifically discussed are considered prima facie clear.)
Regarding claim 1: The composition of claim 1 is understood to be a composition (composition A) comprising (i) a first particle comprising a conditioned medium from a cell culture within the particle and having a first release profile of the conditioned medium. The particle may consist of the conditioned culture medium, or the particle may comprise the first conditioned medium in combination with another component (e.g. a polymer). The term “particle” does imply a solid state of matter. Thus liquid conditioned medium will not read on a particle, but particles of lyophilized conditioned medium will.
Regarding claim 2: The composition of claim 2 is understood to be a composition (composition A’) comprising (i) a first particle, as previously described, and (ii) a second particle, said second particle being different than the first particle, said second particle comprising a conditioned medium from a cell culture within the second particle and having a second release profile of the conditioned medium present therein (in the context of the claim it is clear “the conditioned medium” is referring to the conditioned medium within the second particle). The claim specifies that the first and second release profiles must be different. The claim also specifies the combination of the particles produces an extended release profile, which extends beyond the first release profile. This is understood to mean that the release profile of the second particle is longer than the release profile of the first particle. The claim states the conditioned medium present within the first and second particles can be the same or different.
Regarding claim 3: The composition of claim 3 is understood to be a composition (composition A”) comprising (i) a first particle, as previously described, (ii) a second particle, as previously described, and (iii) one or more additional particles, each independently comprising conditioned medium from a cell culture within the one or more additional particles and having a release profile of the conditioned medium present therein (in the context of the claim it is clear “the conditioned medium” is referring to the conditioned medium within the one or more additional particles). The claim specifies that the independent release profile of the one or more additional particles must be different from the first release profile of the first particle, and from the second release profile of the second particle. The claim also specifies the combination of the first, second, and one or more additional particles produces an extended release profile, which extends beyond the first release profile of the first particle and the second release profile of the second particle. This is understood to mean that the independent release profile(s) of the one or more additional particles is/are longer than the first release profile of the first particle and longer than the second release profile of the second particle. The claim states the conditioned medium present within the first, second, and one or more additional particles can be the same or different.
Claim 12 is directed to a method of making a tissue growth scaffold, comprising distributing a composition comprising the composition A’ in a biocompatible polymer. The tissue growth scaffold made by claim 12 is broader than the tissue growth scaffold of claim 7, as the method of claim 12 does not limit the biocompatible polymer to a porous material of biocompatible polymer. The method must result in production of a tissue growth scaffold, which will have the characteristics discussed above in regards to claim 7.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1, 4-12, 14, 16 and 19 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Schilling et al (WO 13/113821).
Schilling et al disclose a method of preparing a cell-free composition, comprising (a) providing cells on/in a first carrier and subjecting said cells to stress, and (b) collecting factors produced by the cells in a second cell-free carrier (See Pg. 13, ln 14-Pg 14, ln 2). Cells types that can be provided on the first carrier include, inter alia, bone marrow stromal stem cells (See Pg. 31, ln 36-Pg 32, ln 26).
Schilling et al teach the second carrier can be a matrix capable of absorbing or trapping the soluble factors (the conditioned medium) (See Pg. 35, ln 5-30). Schilling et al teach the material of the second carrier matrix can be the same as that described for first carrier (See Schilling et al, Pg. 35, ln 11-15). Schilling et al describe the matrix material of the first carrier as including, inter alia synthetic polymers, including polyglycolic acid (PGA), polylactic-co-glycolic acid (PLGA), polylactic acid (PLA), polycaprolactone (PCL), polystyrene and polyethylene terephthalate (PET) (See Pg 33, ln 11-17). The second matrix can be mechanically fragmented after loaded with the conditioned medium (Pg 38, ln 32-Pg 39, ln 15).
Regarding claim 1: The cell-free composition collected in step (b) reads on conditioned medium from a cell culture. The cell-free composition (conditioned medium) is absorbed/trapped in the second carrier matrix. The particles yielded from fragmentation of the second carrier matrix reads on particles comprising conditioned medium from a cell culture. The particles of fragmented matrix necessarily have a first release profile. Thus the particles of fragmented matrix read on the composition of claim 1 (i.e. Composition A).
Regarding claims 4, 7-12 and 14: Schilling teach the second carrier can comprise, inter alia, synthetic polymers, including PLGA, PLA, PGA and/or PCL. These are each biocompatible, bioerodible polymer materials. These species anticipate polymer species listed in claims 4, 7-12 and 14.
Regarding claims 5 and 6: Schilling et al teach the cells provided on the first carrier can be bone marrow stromal stem cells (BMSSCs). BMSSCs read on stem cells, progenitor cells, mesenchymal stem cells, and secretory cells (as they secrete factors). Therefore the conditioned culture medium is from a culture of a stem cells, progenitor cell, mesenchymal stem cells, or secretory cell.
Regarding claims 16 and 19: Schilling et al teach the factors secreted by the cells include, inter alia, growth factors, and specifically angiogenic factors (which reads on composition that promotes angiogenesis) (See Pg 19, ln 6-11). Thus, growth factors are specifically collected in/present within the collected second carrier matrix.
Claims 1, 4-6, 9, 10, 16, and 18-20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Riordan et al (US 2012/0276215).
Riordan et al disclose therapeutic compositions comprising medium conditioned by stem cells, the stem cells can be Whartons’ jelly mesenchymal stem cells (See ¶0014). Riordan et al teach various embodiments of their invention. Separate rejections are made over different embodiments.
In one embodiment of the invention the conditioned media is nanoencapsulated into nanoparticles for delivery as a pharmaceutical composition. The nanoencapsulation material may be synthetic polymers, such as polyvinyl alcohol (See ¶0015).
This embodiment reads on the claims as follows: Regarding claim 1: The nanoparticles comprising the stem cell conditioned medium and polymers reads on a composition comprising a first particle comprising conditioned medium. (i.e. Composition A). The nanoparticles will necessarily have a first release profile.
Regarding claims 4, 9 and 10: The polymers satisfy the limitation of polymer material (claim 4) and a polymer (claim 6). Polyvinyl alcohol is both biocompatible and bioerodible (claims 9 and 10).
Regarding claims 5-6: The conditioned medium is from Wharton’s jelly mesenchymal stem cells.
Regarding claims 16, 18 and 20: Riordan et al teach additional anti-inflammatory agents can be provided with the conditioned media, including inter alia, NSAIDS and/or aspirin (See ¶0019). Anti-inflammatory agents also read on inflammation regulators (claim 16). Aspirin reads on an anti-thrombogenic (claim 20).
Regarding claim 16 and 19: The stem cells can secrete VEGF (¶0021). VEGF is a growth factor that promotes angiogenesis.
In a different embodiment, the conditioned media is lyophilized (See ¶0035).
This embodiment reads on the claims as follows:
Regarding claim 1: The lyophilized conditioned media, per se, reads on a composition comprising a first particle comprising conditioned medium. (i.e. Composition A). The particles of the lyophilizate are each particles consisting of conditioned medium. The particles will necessarily have a first release profile.
Regarding claims 5-6: The conditioned media is medium from culture of Wharton’s Jelly mesenchymal stem cells Thus the conditioned medium is from mesenchymal stem cells.
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.
Claims 1, 4-16 and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Schilling et al (WO 13/113821), in view of Vroman et al (Materials, 2009).
The teachings of Schilling et al are set forth above.
Regarding claims 7-15: As discussed above, Schilling et al teach the second carrier matrix can be made of synthetic polymer suitable for drug delivery. Schilling et al provide several examples, including PLA, PLGA and PCL (anticipating claims 7-12 and 14). Schilling et al does not teach all species claimed, particularly species from claims 13 or 15. However, at the time the application was filed numerous biocompatible polymer materials were known as suitable for use in drug delivery (See Vroman et al, Materials, 2009), including, inter alia, polydioxanone (pg 311) and polycarbonate (See Pg 312).
Given that both Schilling et al and Vroman et al teach polymers suitable for drug delivery, it would have been prima facie obvious to have substituted any of the polymers taught by Vroman et al, in particular polydioxanone and polycarbonate, in for the PLA, PLGA and/or PCL used by Schilling et al. One would have had expected similar results given that all were recognized as generally biocompatible polymers that can be used in drug encapsulation and delivery. This conclusion of obviousness is based on the ‘substitution rationale’.
Claims 1, 4-6, 9, 10 and 16-20 are rejected under 35 U.S.C. 103 as being unpatentable over Riordan et al (US 2012/0276215).
The teachings of Riordan et al are set forth above. The embodiment wherein the conditioned medium is encapsulated into nanoparticles for delivery as a pharmaceutical composition, wherein the nanoencapsulation material is a synthetic polymer, is relied upon.
Regarding claims 1, 4-6, 9, 10, 16, and 18-20: Riordan et al anticipates these claims for the reasons set forth above.
Regarding claim 17: Riordan et al teaches additional agents can be added to the stem cell conditioned media to treat specific conditions (See ¶0019). A wide variety of conditions are contemplated by Riordan et al (See ¶0019 and claim 24). Infections is listed as one of the conditions (See claim 24).
Official notice is taken that IL-2, IL-12 and IFN-gamma each trigger an immune response and activate NK cells.
In cases of infection, activation of the immune system is desired to combat the infection. Therefore, for the embodiments when the composition of Riordan et al is intended to treat infections, it would have been prima facie obvious to have further includes pro-inflammatory agents IL-2, IL-12 and/or IFN-gamma into the nanoparticles for activation of the immune system. One would have had a reasonable expectation of success because Riordan eta l teaches that additional active agents can be selected for the condition to be treated and loaded into the stem cell conditioned media.
Claims 1 and 4-20 are rejected under 35 U.S.C. 103 as being unpatentable over Riordan et al (US 2012/0276215), in view of Vroman et al (Materials, 2009).
The teachings of Riordan et al are set forth above. The embodiment wherein the conditioned medium is encapsulated into nanoparticles for delivery as a pharmaceutical composition, wherein the nanoencapsulation material is a synthetic polymer, is relied upon.
Regarding claims 1, 4-6, 9, 10, 16, and 18-20: Riordan et al anticipates these claims for the reasons set forth above.
Regarding claim 17: Riordan et al renders obvious this claim for the reason set forth above.
Regarding claims 7-15: As discussed above, Riordan et al teach the nanoparticle can be made of any suitable biocompatible polymer. Riordan et al give a list of examples at ¶0015).
Riordan et al does not teach all species claimed, particularly species from claims 8-15. However, at the time the application was filed numerous biocompatible polymer materials were known as suitable for use in drug delivery (See Vroman et al, Materials, 2009), including, inter alia, polydioxanone (pg 311) and polycarbonate (See Pg 312).
Given that both Riordan et al and Vroman et al teach polymers suitable for drug delivery, it would have been prima facie obvious to have substituted any of the polymers taught by Vroman et al, in particular polydioxanone and polycarbonate, in for the polymer material used by Riordan et al. One would have had expected similar results given that all were recognized as generally biocompatible polymers that can be used in drug encapsulation and delivery. This conclusion of obviousness is based on the ‘substitution rationale’.
Claims 1-6, 9, 10, and 16-20 are rejected under 35 U.S.C. 103 as being unpatentable over Riordan et al (US 2012/0276215), in view of Little et al (US 2012/0172456).
The teachings of Riordan et al are set forth above. The embodiment wherein the conditioned medium is encapsulated into nanoparticles for delivery as a pharmaceutical composition, wherein the nanoencapsulation material is a synthetic polymer, is relied upon.
Regarding claims 1, 4-6, 9, 10, 16, and 18-20: Riordan et al anticipates these claims for the reasons set forth above.
Regarding claim 17: Riordan et al renders obvious this claim for the reason set forth above.
Regarding claims 2 and 3: Riordan et al does not teach encapsulating the conditioned medium in different nanoencapsulation materials to produce a variety of nanoparticles having different release profiles.
Little et al disclose methods for making a modified release composition, said composition comprising different populations of sustained release microparticles, wherein each population of microparticles contains at least one active agent and at least one biodegradable polymer matrix, and wherein the at least one biodegradable polymer matrix of each population of microparticles is different, such that each population of microparticles has a different release prolife. Little et al teach that by providing the same active agent in multiple populations of microparticles, each population of microparticles having a different release profile, the overall composition can provide sustained release of the active agent over greater periods of time due to differentiation release profiles of each population. Little et al teach modified release compositions comprising two or three different microparticle populations (See Little et al, ¶0004-0018; claims 11-12). Little et al teach this modified release composition is suitable for sustained delivery of, inter alia, proteins and/or small molecules (See Little et al, ¶0054-0056). Little et al provide guidance on how to manipulate the release rate of particles (See Little et al, ¶0079-0088).
It would have been prima facie obvious to one having ordinary skill in the art, at the time the application was filed, to modify the nanoencapsulated cell conditioned culture medium of Riordan et al to be a modified release composition comprising two or three different nanoparticle populations, each nanoparticle population comprising the cell conditioned medium, but different polymer matrices such that the different populations have different release profiles. The motivation to make this modification is provided in Little et al. Specifically, one would have been motivated to make the modification so that the cell culture conditioned medium, when delivered as nanoparticles, has sustained release over a longer period than a single population of nanoparticles. Little et al teach prolonged, sustained release is desirable in pharmaceutical therapies. One would have had a reasonable expectation of successfully generating the different nanoparticle populations based on the teachings of Little et al.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 11684574.
Although the claims at issue are not identical, they are not patentably distinct from each other because the patented claims anticipate and/or render obvious the instant claims.
Regarding claims 1-2: Patented claim 9 is drawn to a method that will produce first and second particles having the same constitution as the first and second particles of instant claims 1 and 2.
Regarding claims 4 and 7-15: Patented claim 15 teaches the polymers of claims 4 and 7-15.
Regarding claims 5 and 6: Patented claim 16 teaches the conditioned media is from the same cell types as claim 6.
Regarding claims 16-20: The cells cultured to produce the conditioned media will necessarily produce a variety of growth factors, cytokines and inflammatory regulators. Inclusion of additional well known active agents, such as those recited in claims 17-20 are considered prima facie obvious. Inclusion of additional active agents for predictable result of providing the predictable benefit of the active agents is obvious based on the “combining known equivalents” rationale.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALLISON M FOX whose telephone number is (571)272-2936. The examiner can normally be reached M-F 10-6 EST.
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/ALLISON M FOX/Primary Examiner, Art Unit 1633
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