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 .
The preliminary amendment to the claims dated 11/20/2023 are under consideration. Claims 51-70 are under consideration.
Claim Objections
Claims 51-70 are objected to because of the following informalities: Claims added by amendment require the status identifiers, “New”, which has been omitted from the newly added claims. Going forward, please provide the correct status identifiers. Appropriate correction is required.
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 51-70 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.
Independent claim 51, step (d) recites, “initiating further propagation in adherent or suspension cultures”. However, the step does not specify what is being further propagated (i.e. the spheroids or organoids? Cells therefrom? Some other entity not recited?). As such, the metes and bounds of the claim are not clearly and distinctly pointed out, and therefore, the claim is indefinite.
Further, claims 52-70 all depend upon claim 51. As such, they also comprises the above indefinite subject matter.
Claim Interpretation
[0065] As defined herein, a “spheroid” or “organoid” is a type of 3D cell modeling that can simulate a live cell's environmental conditions as compared to a 2D cell model, specifically with the reactions between cells and the reactions between cells and the matrix.
Thus the definition of a spheroid or organoid, the broadest reasonable interpretation of “muscle spheroids or organoids” as claimed and formed in step (b) encompasses a 3D cell culture/structure comprising muscle cells or muscle cell precursors.
Step (b) recites “expanding the muscle cells or the muscle precursors from the non-human animal source in presence of an effective concentration of insulin-like growth factor (IGF)…to facilitate formation of muscle spheroid or organoids”. “Expanding” has not been specifically definite by the specification. “Expanding” in the cell culture art can often be synonymous with “proliferating”. However, the instant claims recite the end result of step b is the formation of muscle spheroids or organoid (i.e. muscle 3D culture/structure comprising muscle cells or muscle precursors). Further step c requires the formation of the claimed spheroids or organoids to be able to harvest them as claimed. As such, “expanding” in the context of the claim is being interpreted as including both expanding, differentiating, culturing in such a manner that the claimed spheroid or organoids form.
Regarding step c, the specification does not define the term “harvesting”. As such, the spheroid or organoid can be harvested in an art recognized understanding of “harvesting”. Akadeum Life Sciences (printout from https://www.akadeum.com/blog/cell-harvesting/?cn-reloaded=1, published Feb 2021, pp. 1-5) states, “The process of isolating target cells from a growth medium is called cell harvesting.” See page 2 of printout. As such, the breadth of “harvesting the muscle spheroid or organoids as claimed encompasses changing the medium in which the spheroid/organoids are cultured.
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.
(1) Claim(s) 51, 53-67, and 69-70 is/are rejected under 35 U.S.C. 103 as obvious over Ben-Arye (WO2019016795 A1 pub date:1/24/2019; of record in IDS and ISR).
Regarding claim 51, Ben-Arye teaches a method for producing an edible composition comprising: (a) incubating a 3D porous scaffold and a plurality of cell types comprising: (a) myoblast or progenitor (i.e. muscle precursor) thereof; and at least one of: (ii) at least one type of ECM secreting cell (i.e. muscle or muscle precursor) or (iii) endothelial cells or progenitor cells (i.e. muscle cell or precursor). See page 2, [009]. Ben-Arye also more specifically discloses. Ben-Arye teaches seeding and culturing bovine satellite cells (BSC) on a porous 3D TSP scaffold (See p 32, [0154]). Thus Ben-Arye teaches (a) acquiring muscle cells and muscle precursor cells form a non-human animal source as claimed. Ben-Arye further teaches that IGF was added to the culture to promote the formation of myotubes (p. 32, [0154]). Ben-Arye also teaches that the seeding and culturing are in a culture vessel or plate (for example, See figure 2B; p. 38). This teaches expanding the muscle cells or precursor in the presence of an effective amount of IGF in a culture vessel or culture plate to facilitate the formation of muscle spheroids or organoids as claimed. Ben-Arye further teaches the TSP was 100-1000 µm pore size which can be used for cell culture (p. 27, example 1). Ben-Arye further teaches medium was replaced every other day . After a week, medium was changed every to BSC for an additional week (p. 25, [0134]). These teachings encompass the limitations of (c) harvesting the muscle spheroids or organoids”. Ben-Arye does not expressly state that they harvested “when the average diameter of the muscle spheroid or organoids is about 100 micrometers or greater. However as discussed above, the TSP scaffold is 100 micrometers or greater upon which the BSC and others are harvested. As such, when the medium is changed every other day, as taught by Ben-Arye, the spheroids/organoids must be 100 micrometers or greater. As such, Ben-Arye teaches the size of the spheroids/organoids when they are being harvested. Further the above teachings by Ben-Arye also teaches the limitations of (d) inhibiting further propagation because the culture is continued for at least one week after adding differentiation factors. Ben-Arye is silent as to whether the culture is adherent or suspension culture. However, Ben-Arye teaches culture in a culturing vessel, multi-welled plate with no other structures other than medium. As such, the cultures taught by Ben-Arye has to be either adherent to the culture dish or suspension culture in the medium, as claimed. Thus, Ben-Arye teaches all of the require limitations of the claims.
Regarding claim 53, Ben-Arye teaches acquiring BSC which a muscle precursor cells as claimed.
Regarding claim 54, Ben-Arye teaches that adding IGF-1 resulted in myotubes and adding EGF resulted in myotubes in all expansion medium (p. 32, [0154]). The claim and the specification do not define a specific means of screening for metabolic activity. As such the breadth of screening for metabolic activity includes observing a biological function that the living cell does because all of the activities of the living cell are demonstration that metabolic activity is occurring.
Regarding claim 55, Ben-Arye teaches the breadth of harvesting in this claim for the same rationale discussed above.
Regarding claim 56, Ben-Arye teaches examples of only culturing with BSC (p. 32, [0154]). As such, Ben-Arye teaches a single cell type.
Regarding claim 57, Ben-Arye teaches that endothelial cells can also be culture with the BSC (p. 25 and as discussed above). As such, Ben-Arye teaches two or more cell types.
Regarding claim 58, Ben-Arye teaches the use of bovine endothelial cells (BEC) and BSC as discussed above. Further, Ben-Arye teaches another variant that cultures with BSC, bovine smooth muscle cells (MSC), and Skeletal microvascular endothelial cells (SkMVEC). See Example 14 for example.
Regarding claim 59, Ben-Arye teaches a TSP scaffolding as discussed above.
Regarding claim 60, Ben-Arye expressly teach a scaffold free variant. However, Ben-Arye teaches other non-scaffold method are known mediums are known in the prior art such as hydrogels [00157].
Regarding claim 61, Ben-Ayre teaches the plurality of cell types are derived from non-human cells. In some embodiments, the plurality of cell types are derived from non-human cells selected from the group consisting of: mammals, birds, fishes, invertebrates, reptiles, amphibians, and combinations thereof. In some embodiments, the plurality of cell types are derived from mammals. In some embodiments, the plurality of cell types are derived from non-human mammals. In some embodiments, the plurality of cell types are derived from livestock mammals. As used herein, "livestock" comprises any domestic mammal, semi-domestic mammal or captive wild mammal. Non-limiting examples of non-human mammals include: antelope, bear, beaver, bison, boar, camel, caribou, cattle, deer, elephant, elk, fox, giraffe, goat, hare, horse, ibex, kangaroo, lion, llama, moose, peccary, pig, rabbit, seal, sheep, squirrel, tiger, whale, yak, and zebra, or combinations thereof. In some embodiments, the plurality of cell types are derived from bird cells. Non-limiting examples of birds include: chicken, duck, emu, goose, grouse, ostrich, pheasant, pigeon, quail, and turkey, or combinations thereof. In some embodiments, the plurality of cell types are derived from fishes. Non-limiting examples of fishes include: bass, catfish, carp, cod, eel, flounder, fugu, grouper, haddock, halibut, herring, mackerel, mahi, marlin, orange roughy, perch, pike, pollock, salmon, sardine, shark, snapper, sole, swordfish, tilapia, trout, tuna, and walleye, or combinations thereof. In some embodiments, the plurality of cell types are derived from invertebrates. Non-limiting examples of invertebrates include: lobster, crab, shrimp, clams, oysters, mussels, and sea urchin. In some embodiments, the plurality of cell types are derived from reptiles. Non-limiting examples of reptiles include: snake, alligator, and turtle. In some embodiments, the plurality of cell types are derived from amphibians. Non- limiting example of amphibians includes frogs. See [0076].
Regarding claim 62, Ben-Arye teaches the inclusion of ECM secreting cells which secrete heterologous ECM. Further Ben-Arye discloses resuspension in fibrinogen solution (i.e. a heterologous ECM). See [0134].
Regarding claim 63, Ben-Arye does not disclose the claimed percentages of fibronectin/hydrogel as claimed. However, the percentages are concentration ranges. MPEP § 2144.05 (II) states the following:
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In reAller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In reHoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc.v.Biocraft Lab. Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In reKulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997); Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree “will not sustain a patent”); In re Williams, 36 F.2d 436, 438 (CCPA 1929) (“It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions.”). See also KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007) (identifying “the need for caution in granting a patent based on the combination of elements found in the prior art.”).
A review of the specification fails to provide evidence that the claimed concentration are critical. Absent such evidence it would have been obvious to an artisan of ordinary skill at the time of effectively filing Ben-Arye to try a finite number of possible concentration of the fibronectin/hydrogel component to predictably arrive at the claimed concentration through routine optimization. An artisan would have a reasonable expectation of success in optimizing the concentrations because methods of determining optimal fibronectin/hydrogel concentrations were long established in the art as demonstrated by Ben-Arye. Thus Ben-Arye renders the instantly claimed concentration above.
Regarding claim 64, Ben-Arye teaches that the 3D cultures are expanded in medium comprising 10 mg/ml bovine FGF, 62 ng/ml EGF, and 100 ng/ml IGF-1 ([0128]).
Regarding claim 65, Ben-Arye teaches 100 ng/ml IGF-1 as discussed above. However, about 1 to about 50 ng/ml concentrations of IGF-1 is not taught.
However, MPEP § 2144.05 (II) states the following:
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In reAller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In reHoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc.v.Biocraft Lab. Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In reKulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997); Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree “will not sustain a patent”); In re Williams, 36 F.2d 436, 438 (CCPA 1929) (“It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions.”). See also KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007) (identifying “the need for caution in granting a patent based on the combination of elements found in the prior art.”).
A review of the specification fails to provide evidence that the claimed concentration are critical. Absent such evidence it would have been obvious to an artisan of ordinary skill at the time of effectively filing Ben-Arye to try a finite number of possible concentration of the precursor component to predictably arrive at the claimed concentration through routine optimization. An artisan would have a reasonable expectation of success in optimizing the concentrations because methods of determining optimal IGF-1 concentrations were long established in the art as demonstrated by Ben-Arye. Thus Ben-Arye renders the instantly claimed concentration above.
Regarding claim 66, Ben-Arye discloses that the media is changed every other day as discussed above. As such, Ben-Arye teaches harvested at least 2 days after expanding.
Regarding claim 67, Ben-Arye discloses for an additional week after adding differentiation medium as discussed above. As such, Ben Arye teaches harvesting at least 5 days after expanding.
Regarding claim 69-70, Ben-Arye discloses multiple 3D cell culture scaffold constructs, one comprising BSC solely, one comprising BSC and BEC, and one comprising BSC, BEC, skMEV, as described above. Given the end-result of the method of Ben-Arye is intended to produce an edible product. An artisan of ordinary skill could easily combine any of these three different types of constructs to provide enough mass to arrive at an edible product with a reasonable expectation of success.
As such, the prior art of Ben-Arye renders obvious the claims because it adequately teaches or suggests all the limitations of the claims.
(2) Claim(s) 51 and 68 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ben-Arye (WO2019016795 A1 pub date:1/24/2019; of record in IDS and ISR) as applied to claims 51, 53-67, and 69-70 above, and further in view of Zuchowska (Zuchowska et al. Analytica Chimica Act1 (2017) 990:110-120) and Agrawal (Agrawal et al. Lab Chip 2017:17(20):3447-3461).
Regarding the microchip embodiments of claims 51 and 68, Ben-Arye teaches the limitations of these claims as discussed above. Ben-Arye does not teach the limitations of expanding the muscle cells or precursors to form a spheroids or organoids in a microchip (claim 51), more particularly a microchip with the claimed structural elements (claim 68).
However, before the time of effective filing, Zuchowska teaches a method culturing 3D lung spheroid in wells a microfluidic chip (abstract). Zuchowska teaches that the microfluidic chip is fabricated to comprise a microchambers with network of microchannels with inverted dome and a diameter of about 100 micrometers. See figure 1 on page 112 and page 111, col 2, section 2.1. Zuchowska further teaches that the design of the microwells comprising microchamber are have a spherical bottom which allows for more effective aggregation of cells and spheroids to stay connected and have a design dedicated to spheroid formation and culture (page 112 and page 111, col 2, section 2.1).
Agrawal teaches engineered skeletal muscle tissues can be used for in vitro studies that require physiologically relevant models of native tissues. Herein, we describe the development of a three-dimensional (3D) skeletal muscle tissue that recapitulates the architectural and structural complexities of muscle within a microfluidic device. See abstract. Organs-on-chips, which contain engineered microtissues that capture the physiological complexity of the native tissues within a continuous perfusion device, can be developed in a reproducible and cost-effective manner. These microphysiological systems also have the potential to supplement preclinical animal studies during drug discovery and development in order to improve the translatability of the drugs to the clinic. See page 2, paragraph 1.
Thus, it would have been obvious to an artisan of ordinary skill before the time of effective filing to produce the muscle spheroids or organoids of Ben-Arye in the microchip taught by Zuchowska using the method of Ben-Arye to predictably arrive at the limitations of the claims. One would have a reasonable expectation of success because Zuchowska demonstrates successful spheroid formation and culture can be done in their microchip design. Further, the artisan would be motivated to use the microchip of Zuchowska because it has been design specifically to facilitate spheroid formation and culture as taught by Zuchowska. Further an artisan would particularly be motivated to make a muscle spheroid microchip because Agrawal teaches engineered skeletal muscle tissues can be used for in vitro studies that require physiologically relevant models of native tissues. Herein, we describe the development of a three-dimensional (3D) skeletal muscle tissue that recapitulates the architectural and structural complexities of muscle within a microfluidic device. Organs-on-chips, which contain engineered microtissues that capture the physiological complexity of the native tissues within a continuous perfusion device, can be developed in a reproducible and cost-effective manner. These microphysiological systems also have the potential to supplement preclinical animal studies during drug discovery and development in order to improve the translatability of the drugs to the clinic.
Thus, Ben-Ayre in further view of Zuchowska and Agrawal teach the limitations of the claims rendering them obvious.
(3) Claim(s) 51 and 52 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ben-Arye (WO2019016795 A1 pub date:1/24/2019; of record in IDS and ISR) as applied to claims 51, 53-67, and 69-70 above, and further in view of Chromiak (Chromiak et al. In vitro Cell Dev Biol.-Animal 1998 34:694-703.)
Ben-Ayre teaches the limitations of the claimed method as discussed above. Ben-Ayre does not teach the expanding (claim 51) and propagating (claim 52) the muscle spheroid/organoid in a bioreactor. However, long before effective filing, Chromiak teaches that muscle organoids can be expanded and propagated in perfusion bioreactor systems (abstract). Perfusion techniques in which differentiated avian and mammalian muscle organoids can be maintained for up to 13 and 30 d, respectively, under conditions where their metabolism is constant, and reliable biochemical and morphological assays can be performed. See page 701, col 1, paragraph 1 of Discussion section. Continuous medium perfusion prevents the large shifts in glucose, nutrients, and secreted molecules in the medium, including autocrine and paracrine growth regulatory molecules that occur in static, nonperfused cultures with intermittent medium changes. Perfusion also prevents the local accumulation of deleterious metabolic products such as lactic acid and associated H + ions. Long-term maintenance of cells in a closed-loop perfusion system also reduces the potential for introducing contaminants. Finally, eliminating the necessity of routine culture medium changes is important for experiments in which daily access to the cultured cells is not possible. See page 694, col 1, paragraph 1).
Thus it would have been obvious to an to an artisan of ordinary skill before the time of effective filing to do the method of forming and propagating muscle spheroids/organoids, as taught by Ben-Ayre, in a perfusion bioreactor, as taught by Chromiak to predicably arrive at the limitations of the claims. One would have a reasonable expectation of success because Chromiak demonstrates stable long formation and propagation of muscle organoids in a perfusion bioreactor. Further one would be motivated to do the method of Ben-Ayre in a bioreactor because continuous medium perfusion prevents the large shifts in glucose, nutrients, and secreted molecules in the medium, including autocrine and paracrine growth regulatory molecules that occur in static, nonperfused cultures with intermittent medium changes; perfusion also prevents the local accumulation of deleterious metabolic products such as lactic acid and associated H + ions. Long-term maintenance of cells in a closed-loop perfusion system also reduces the potential for introducing contaminants; and finally, eliminating the necessity of routine culture medium changes is important for experiments in which daily access to the cultured cells is not possible. Thus Ben-Arye in view of Chromiak renders the claims obvious.
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 53 and 58 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for the claimed method as claimed using precursor cells that are not embryonic stem cells, does not reasonably provide enablement for the use of embryonic stem cells. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
While determining whether a specification is enabling, one considers whether the claimed invention provides sufficient guidance to make and use the claimed invention, if not, whether an artisan would require undue experimentation to make and use the claimed invention and whether working examples have been provided. When determining whether a specification meets the enablement requirements, some of the factors that need to be analyzed are: the breadth of the claims, the nature of the invention, the state of the prior art, the level of one of ordinary skill, the level of predictability in the art, the amount of direction provided by the inventor, the existence of working examples, and whether the quantity of any necessary experimentation to make and use the invention based on the content of the disclosure is “undue”.
Nature of Invention: A method of claim meat product comprising producing muscle spheroids/organoids.
Breadth of the Claims: Claims 53 and 58 are narrow species claims identifying the species of precursor cells used in the claimed method. The species include embryonic stem cells from any species of non-human animal.
Specification Guidance: The specification, while contemplating differentiation of embryonic stem cells into muscle cells and muscle precursor, does not provide any specific guidance a means of obvious embryonic stem cells from all non-human species. As such, the specification fails to enable embodiments with embryonic stem cells.
State of the prior Art: At the time of effective filing, successful derivation of true embryonic stem cells that predictably maintain pluripotency had only been established for humans and rodents. While embryonic stem cell can be isolated from the inner cell mass of other non-human embryos, these isolated inner cell mass cells are unable to maintain pluripotency. Post-filing some progress has been made in establishing bovine embryonic stem cells. However, they fail to be predictably maintain pluripotency and none have been reported to contribute to a chimeric embryo. Given these unstable and unpredictable status of pluripotency in these non-human embryonic stem cells, propagation of embryonic stem cells in non-human species other than rats and mice are not possible. See Navarro et al. (Anim Reprod. 2024;21(3):e20240029 | https://doi.org/10.1590/1984-3143-AR2024-0029 pp. 1-15).
As such, the state of the art teaches that other than rodents, non-human embryonic stem cell fail to be predictably be available for use in the claimed method. As such, the art fails to supplement the shortcomings of the specification.
Amount of Experimentation: As discussed above, non-human embryonic stem cells were not predictably available and could not be propagated that the time of effective filing. Addition methods of culturing, maintaining, and propagating non-human embryonic stem cells would need to be development before successful use of non-human embryonic stem cells as a precursor source in the instant method can be achieved. This level of experimentation goes beyond routine optimization into new discovery experimentation. As such, the level of experimentation would be undue.
In conclusion, the embodiments of the claims that expressly recited embryonic stem cells lack enable because neither the specification nor the art provide a predictable means of obtain embryonic stem cells that are stably pluripotent and can be propagated. Further the amount of experimentation need to possibly make and use the claimed method with non-human embryonic stem cells goes beyond routine predictable experimentation into new and unpredictable means of new discovery. As such, the amount experimentation is undue.
No claims are 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