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 .
Election/Restrictions
Applicant’s election without traverse of Group I in the reply filed on 12/4/2025 is acknowledged.
Claims 7-11 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 12/4/2025.
Regarding the species election, Applicant elected without traverse: Neuronal cell reprogramming method, neuronal cell differentiation-inducing medium, expression of neuron specific markers, and neurons for differentiated cell type.
Claims 1-6 and 11-17 are under consideration.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-6 and 11-17 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
(1) Claim 1 recites, “extracellular vesicle containing exosomes isolated from the culture medium”. The first step recites “a mixture of differentiated or non-differentiated cells and a culture medium”. However, there is no implication that “a culture medium” in the first step has “extracellular vesicle containing exosome”. As such, the scope of the culture medium in the first step is not apparent because it is not apparent if it requires the presence of extracellular vesicles containing exosome or not.
Further, claim 1 recites, “mixing the differentiated or non-differentiated cells with extracellular vesicles containing exosomes”. However, it does not specify when this mixing is to occur. So it is not apparent if it is some type of pretreatment prior to the first recited subjecting step or intended to occur at a later time in the method.
Even further, claim 1 recites that last step of “culturing the mixture for a pre-determined time”. However prior to this recitation, there are two recited mixtures, the first being “a mixture of differentiated or non-differentiated cells and a culture medium” the second being the mixture that results from “mixing the differentiated or non-differentiated cells with extracellular vesicles”. As such, the last step reciting “the mixture” lack sufficient antecedent basis and is definite because it is not apparent to which of the mixtures it refers.
Overall the intended scope of the claim is not apparent for the reasons discussed above.
For purposes of identifying relevant prior art, Claim 1 will be interpreted as a reprogramming method comprising subjecting a mixture of differentiated or non-differentiated cells with exosome and culture medium to physical stimulation and culturing for at 1 to 6 days or until reprogrammed cells are obtained.
Claims 2-6 and 11-17 are dependent upon claim 1 and therefore also comprise the indefinite subject matter discussed above.
(2) Claim 2 is rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of physical stimuli is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: the listed species, “ultrasonic wave, laser, plasma, light-emitting diodes, electrical stimulation, chemical exposure, heat shock, or acid treatment are recognized as different and distinct classes of physical stimuli. Each having physical structural/functional properties. As such, the would not be recognized as one that could be substituted for the other.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
(3) Claim 4 is rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of culture mediums is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: Each of the recited species of culture medium comprise different chemical structures comprising different differentiation factors that ultimately result in structural different cell types.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
(5) Claim 5 recites, “further comprising: treating ultrasonic…”. Claim 5 dependents upon claim 1 and there are no ultrasonic waves that one could subject to treatment. Further the claim specifies the ultrasonic waves “having an output intensity…for 1 to 20 minutes”. This recitation would suggest that the ultrasonic waves are being used to treat something as opposed to treating ultrasonic wave as the claim literally states. As such, it is not apparent if the claim intends to treat something will ultrasonic waves or if the ultrasonic waves are somehow being treated.
(6) Claim 6 recites, “wherein the ultrasonic wave treatment”. Claim 6 depends upon claim 1 which has no recitation or implication of ultrasonic wave treatment. As such, the recitation lack sufficient antecedent basis and is indefinite because it is not apparent to what “the ultrasonic wave treatment” refers.
(7) Claim 13 recites, “exosomes express any on pluripotent or triploblastic marker”. This recitation is indefinite because it is not apparent how exosomes “express” markers because they are just lipid membranes and do not have any of the machinery to express protein markers as claimed.
(8) Claim 15 recites, “the reprogrammed cells have different cell expression types”. “Different cell expression types” is comparative language. However, “different” relative to what?
(9) Claim 13 rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of exosomes expressing different markers is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: each of the recited species express marker proteins of different cell lineages. As such, each species is structurally and functionally divergent and recognized a different classes of molecules, one not substitutable for the other because they impart different effects.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
(10) Claim 15 is rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of reprogrammed cell types is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: each species of cell type has a different structure and function and are arrives upon uses different reprogramming factors. As such, the different cell type are not substituted one for the other in the claimed method.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
(11) Claim 17 rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of differentiated cells expressing different markers is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: each of the recited species express marker proteins of different cell lineages. As such, each species is structurally and functionally divergent and recognized a different classes of molecules, one not substitutable for the other because they impart different effects.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
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.
(1) Claims 1-6 and 11-16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 of U.S. Patent No. 11,773,387. Although the claims at issue are not identical, they are not patentably distinct from each other because the instant and patent claims have non-mutually exclusive overlapping scope.
Regarding claim 1, patent claim 1 discloses a method of reprogramming differentiated cells into pluripotent cells, comprising: treating a culture medium by applying energy to the culture medium to enhance spheroid-forming efficiency of differentiated cells prior to mixing the differentiated cells with the culture medium, wherein the energy applied to the culture medium is ultrasonic energy having an output intensity of 3 W/cm.sup.2 to 7 W/cm.sup.2 for 7 to 13 minutes; mixing the differentiated cells with the treated culture medium; applying ultrasonic energy to the mixture of the treated culture medium and the differentiated cells, and culturing the mixture for a predetermined time to form spheroids, wherein said spheroids have cells with pluripotent characteristics; wherein the differentiated cells are mammal-derived fibroblast cells; wherein the culture medium is selected from the group consisting of an embryonic stem cell culture medium, and a stem cell differentiation-inducing medium; wherein the applying ultrasonic energy to the mixture of the treated culture medium and the differentiated cells is performed at an output intensity of 0.5 W/cm.sup.2 to 3 W/cm.sup.2 for 1 to 5 seconds. Patent claim 1 does not each exosome in the medium mixed with the differentiated or non-differentiated cells that are treated with ultrasound. However, the specification of the patent teaches that the mechanism by which reprogramming occurs includes the release of exosome comprising undifferentiated marker that enter surrounding cells and reprogram. This occurs by subjecting the differentiated cells to the ultrasound. As such, while the patent claim is silent as to the presence of exosome, inherently they are being release into the medium and taken up by surrounding cells when the recited subjecting to ultrasonic energy. As such, patent claim 1 discloses a species of instant claim 1.
Regarding claim 2, patent claim 1 discloses ultrasonic energy as discussed above.
Regarding claim 3, patent claim 1 discloses differentiated cells are fibroblast cells (i.e somatic cells as claimed).
Regarding claim 4, patent claim 1 discloses the medium as an embryonic stem cell medium (i.e. stem cell culture medium as claimed).
Regarding claim 5, patent claim 1 discloses treating a culture medium by applying energy to the culture medium to enhance spheroid-forming efficiency of differentiated cells prior to mixing the differentiated cells with the culture medium, wherein the energy applied to the culture medium is ultrasonic energy having an output intensity of 3 W/cm.sup.2 to 7 W/cm.sup.2 for 7 to 13 minutes. Thus patent claim 1 discloses a range that fall within the ultrasonic wave output intensity claimed.
Regarding claim 6, patent claim 1 discloses applying ultrasonic energy to the mixture of the treated culture medium and the differentiated cells is performed at an output intensity of 0.5 W/cm.sup.2 to 3 W/cm.sup.2 for 1 to 5 seconds as claimed.
Regarding claim 11, patent claim 1 discloses spheroid forming in culture which is suspension culture as claimed. Further, patent claim 3 discloses wherein the culturing is carried out for 3 days to 10 days using a suspension culture method or a monolayer culture method.
Regarding claim 12, since the claim does not recite any active isolation step and the exosome recovery limitations are present in a wherein clause, it is also not an active step in the method. As such, it describes a possible capacity to isolate by centrifugation. Further, the claim as written seems to suggest that the exosome are returned to the same cells and cell culture medium making the mixture the same as a mixture comprising the cells and the medium, wherein the cell release the exosome into the medium. As such means of isolating and centrifuging the cells do not impart a structural or functional distinction to the active steps and materials of the methods. As such, given it broadest reasonable interpretation, claim 12 is an obvious variant of patent claim 1.
Regarding claim 13, patent claim 1 does not expressly disclose that the exosome express the pluripotency markers of the claims. However, as discussed above the exosome and the materials they carry that reprogram the cells inherent to the ultrasonic wave treatment as discussed above. As such, limitations of claim 13 are inherent to the limitations of patent claim 1.
Regarding claim 14, patent claim 3 discloses wherein the culturing is carried out for 3 days to 10 days using a suspension culture method or a monolayer culture method. This range falls within the claimed range.
Regarding claim 15, patent claim 1 discloses the reprogrammed cell is pluripotent.
Regarding claim 16, patent claim 2 discloses wherein the cells having pluripotent characteristics in the spheroids express one undifferentiated marker gene or a three germ layer marker gene selected from OCT3/4, SOX2, NANOG, c-MYC, KLF4, TDGF1, SSEA4, TRA-1-60, PAX6, Nestin, Brachyury, SMA, GATA4, and AFP.
(2) Claims 1-4, 6, 12, 13, 15, and 17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 2 of U.S. Patent No. 11,859,175. Although the claims at issue are not identical, they are not patentably distinct from each other because the instant and patent claims have overlapping, non-mutually exclusive subject matter.
The present application is a divisional filing of its parent application that produced the above patent. MPEP § 804 states:
35 U.S.C. 121 Divisional Applications.
[Editor Note: Applicable to any patent application filed on or after September 16, 2012. See pre-AIA 35 U.S.C. 121 for the law otherwise applicable.]
If two or more independent and distinct inventions are claimed in one application, the Director may require the application to be restricted to one of the inventions. If the other invention is made the subject of a divisional application which complies with the requirements of section 120 it shall be entitled to the benefit of the filing date of the original application. A patent issuing on an application with respect to which a requirement for restriction under this section has been made, or on an application filed as a result of such a requirement, shall not be used as a reference either in the Patent and Trademark Office or in the courts against a divisional application or against the original application or any patent issued on either of them, if the divisional application is filed before the issuance of the patent on the other application. The validity of a patent shall not be questioned for failure of the Director to require the application to be restricted to one invention.
Thus there is a double patenting bar for the “other” inventions filed in a divisional that were not examined due to a restriction requirement made in examination of the parent application that results in a patent. In the instant case, a species election was made in the parent application similar to the ones made in the present application. Applicant elected a group and species in the instant application that are directed to the same subject matter as was elected in the parent application. As such, while the instant application is a divisional filing, the elected grouping and species in the instant application would not be considered “the other invention is made the subject of a divisional application” as filing under 35 USC 121 requires. As such, the instant claims under consideration are not subject to the double patenting bar because the elected subject matter in the instant application is the same as that found in the parent and not subject matter that is a distinct invention found in another grouping found in the parent application.
Regarding claim 1, patent claim 2 teaches A cell reprogramming method comprising: subjecting a mixture of human dermal fibroblasts (HDF) and a culture medium to ultrasonic waves treatment having an output intensity of 0.5 W/cm.sup.2 to 3 W/cm.sup.2 for 1 to 5 seconds which promote an environmental influx for a cell reprogramming, wherein the ultrasonic waves treatment induces damage of the cell membrane which is recovered 2 hours after being subjected to the ultrasonic waves treatment; and culturing, immediately after the ultrasonic waves treatment, the mixture subjected to the ultrasonic waves treatment for a predetermined time to obtain reprogrammed cells, wherein the culture medium is any one of a hepatocyte differentiation-inducing medium, an adipocyte differentiation-inducing medium, or a neuronal cell differentiation-inducing medium, wherein the ultrasonic treatment promotes the environmental influx without introduction of a reprogramming inducing factor other than any one of the differentiation-inducing medium, wherein the reprogrammed cells are any one of neurons expressing any one of PAX6, Nestin, Sox1, Sox2, MAP2, TuJl, GFAP or O4; hepatocytes expressing any one of AFP, HNF1a, HNF4a, CK18 or ALB; or adipocytes stained with oil red O and expressing any one of Pparc2, C/ebpa, aP2 or Fabp4, wherein the environmental influx includes an intracellular influx of genetic materials, chemicals, small molecules, exosomes, or extracellular vesicles containing exosomes released from differentiated or non-differentiated cells subjected to the ultrasonic waves treatment; or culture medium components.
Patent claim 2 does not expressly teach the mixture is subjected ultrasonic treatment for 1-6 days, as recited in instant claim 1. However, determining the amount of time one needs to subject the cells to ultrasonic treatment to successfully arrive at reprogrammed cells is within routine optimization of the claimed invention and thus an obvious variant.
Patent claim 2 does not expressly teach “mixing the differentiated or non-differentiated cells with extracellular vesicles containing exosome isolated from the culture medium”. However, the claims does not recite any active step of isolating the exosomes from the medium and thus this describes a process by which the exosome are made. Patent claim 2 states that the environmental influx includes exosome or vesicles containing exosomes released from the differentiated or non-differentiated cells subjected to the ultrasonic wave treatment. As such, patent claim 2 expressly teaches the mixing of the differentiated or non-differentiated cells with extracellular vesicles containing exosome in the medium. Given that instant claims do not have an active step of actually isolating the exosome and placing them in a medium with the differentiated or undifferentiated cells, the teachings of the patent claim 2 would be an obvious variant of the instant claim 1.
Regarding claim 2, patent claim 1 teaches ultrasonic wave as the species of physical stimulation.
Regarding claim 3, patent claim 2 teaches a fibroblast cell as the differentiated species of cell being subject to ultrasonic wave treatment. Fibroblast are somatic cells as claimed in instant claim 3.
Regarding claim 4, patent claim 2 teaches wherein the culture medium is any one of a hepatocyte differentiation-inducing medium, an adipocyte differentiation-inducing medium, or a neuronal cell differentiation-inducing medium.
Regarding claim 6, patent claim 2 teaches subjecting a mixture of human dermal fibroblasts (HDF) and a culture medium to ultrasonic waves treatment having an output intensity of 0.5 W/cm.sup.2 to 3 W/cm.sup.2 for 1 to 5 seconds.
Regarding claim 12, since the claim does not recite any active isolation step and the exosome recovery limitations are present in a wherein clause, it is also not an active step in the method. As such, it describes a possible capacity to isolate by centrifugation. Further, the claim as written seems to suggest that the exosome are returned to the same cells and cell culture medium making the mixture the same as a mixture comprising the cells and the medium, wherein the cell release the exosome into the medium. As such means of isolating and centrifuging the cells do not impart a structural or functional distinction to the active steps and materials of the methods. As such, given it broadest reasonable interpretation, claim 12 is an obvious variant of patent claim 2.
Regarding claim 13, patent claim 2 does not expressly disclose that the exosome express the markers of the claims. However, the exosome and the materials they carry that reprogram the cells inherent to the ultrasonic wave treatment and inherent to the release exosome taught by claim 2. As such, limitations of claim 13 are inherent to the limitations of patent claim 2.
Regarding claims 15, patent claim 2 teaches the reprogrammed cells are hepatocytes, adipocytes, or neurons as claimed.
Regarding claim 17, patent claim 2 discloses that the hepatocyte, adipocytes, or neurons express the claimed markers.
(3) Claims 5, 11, and 14 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 2 of U.S. Patent No. 11,859,175 in view of Kim (US 11,773,387 effectively filed 12/4/2014).
Regarding claim 5, patent claim 2 teaches the limitations of claim 5 as discussed above. Patent claim 2 does not teach further treating ultrasonic waves having an output of 1W/cm2 to 20 W/cm2 for 1 to 20 minutes in the culture medium before mixing the differentiated or non-differentiated cells with the culture medium.
However, Kim teaches treating a culture medium by applying energy to the culture medium to enhance spheroid-forming efficiency of differentiated cells prior to mixing the differentiated cells with the culture medium, wherein the energy applied to the culture medium is ultrasonic energy having an output intensity of 3 W/cm.sup.2 to 7 W/cm.sup.2 for 7 to 13 minutes ( col 61, claim 1).
Therefore it would have been obvious to an artisan of ordinary skill before the time of effectively filing to add a pretreatment step comprising applying an ultrasonic energy field to the medium before reprogramming the cells, taught by Kim to the reprogramming method of patent claim 2 to predictably arrive at the limitation of instant claim 5. An artisan would have a reasonable expectation of success because the method is a pretreatment step applied to a reprogramming step of Kim. Further, the artisan would have motivation to include the pretreatment step of Kim to the method of patent claim 2 because Kim the pretreatment of the medium enhances spheroid-forming efficiency of differentiated cells prior to mixing the differentiated cells with the culture medium. Thus patent claim 2 in view of Kim renders claim 5 obvious.
Regarding claims 11 and 14, patent claim 2 teaches the method as described above. Patent claim 2 is silent to subjected mixture is cultured by monolayer or suspension culture. However Kim teaches spheroid forming in culture which is suspension culture as claimed (col 61, claim 1). Further, Kim teaches wherein the culturing is carried out for 3 days to 10 days using a suspension culture method or a monolayer culture method (col 63, claim 3). As such, it would have been obvious to an artisan of ordinary skill before the time of effectively filing to do the culture of the cells in the method of patent claim 2 either by suspension or monolayer culture as taught by Kim to predictably arrive at the limitations of claims 11 and 14 with a predictable and reasonable expectation of success.
Relevant Prior Art
Vacanti (WO 2013/163296 A1 pub date:10/31/2013; effectively filed:4/24/2012) is the closest prior art found. Vacanti teaches a method of reprogramming cells to the pluripotent state subjecting the cells to environmental stress stimuli, including ultrasonic wave treatment to induce pluripotency (p.2-3). However, Vacanti does not teach exosomes in the medium or that specific ultrasonic output intensity that would result in the formation of exosome by the cells subject to ultrasonic wave treatment. As the claims require some implication of such exosome becoming present in the medium and Vacanti does not provide such implication. Vacanti does not serve as prior art for the instant claims.
No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARCIA STEPHENS NOBLE whose telephone number is (571)272-5545. The examiner can normally be reached M-F 9-5:30.
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MARCIA S. NOBLE
Primary Examiner
Art Unit 1632
/MARCIA S NOBLE/Primary Examiner, Art Unit 1632