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 II, claims 8-9, 11, 13, 26, and 28 in the reply filed on 02/05/2026 is acknowledged.
Claims 1-5, 7, 14-15, 17, 19-20, 22, 27, and 29 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected groups, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 02/05/2026.
Status of the Claims
Claims 1-5, 7-9, 11, 13-15, 17, 19-20, 22, 26-28, and 29 are currently pending.
Claims 3-5, 7, 11, 13, 17, 19-20, 22, and 26-29 are amended.
Claims 1-5, 7, 14-15, 17, 19-20, 22, 27, and 29 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Invention, there being no allowable generic or linking claim.
Claims 6, 10, 12, 16, 18, 21, and 23-25 are cancelled.
Claims 8-9, 11, 13, 26, and 28 have been considered on the merits.
Non-Patent Literature Request
The art rejections presented below rely on a reference provided in the IDS dated 09/12/2023 by Yoshikazu Kato, entitled “Development of 3D floating iPS cell differentiation induction culture device for industrial use” (Translated). Applicant is thanked for providing a detailed unofficial translation of this document. It is kindly requested that a cleaner/darker copy of the original reference in Japanese is provided to complete an official translation.
Claim Objections
Claim 9 is objected to because of the following informalities: the body of the claim currently reads: “wherein the unsteady operation step comprises an up-and-down reciprocating motion, a left-and-right reciprocating motion, a rotational motion with a variable speed, or a rotational reciprocating motion of the stirring blade, in the steps (b) and (c)”; which can be more clearly conveyed if desired by Applicant. The claim should be amended as follows:
“wherein the unsteady operation in steps (b) and (c)
Appropriate correction is required.
Claim 11 is objected to because of the following informalities: the body of the claim currently reads: “wherein the unsteady operation step varies the operation of the stirring blade at an unsteady cycle in the range of 0.01 Hz to 100 Hz in the steps (b) and (c); or the unsteady operation step in the step (c) is performed for at least 10 days.”; which can be more clearly conveyed if desired by Applicant. The claim should be amended as follows:
“wherein the unsteady operation in steps (b) and (c)
Appropriate correction is required.
Claim 13 is objected to because of the following informalities: the body of the claim currently reads: “wherein the neuronal differentiation medium contains retinoic acid or its derivative in the step (c)”; which can be more clearly conveyed if desired by Applicant. The phrase “in the step (c)” can be deleted as the neuronal differentiation medium in step (c) of claim 8 provides antecedent basis for the neuronal differentiation medium of claim 13 and is therefore redundant. Appropriate correction is required.
Specification
The use of the following terms which is a trade name or a mark used in commerce, has been noted in this application:
Matrigel® appears 24 times in the specification in at least table 1, [0044], [0050], [0068], [0111], [0112], [0116], and [0166]
StemFit® in Table 1
Knockout™ serum replacement in Table 1
GlutaMAX® in Table 1
The terms should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Drawings
The specification contains references to various colors including gray, blue, red, and green in at least the descriptions of Figures 5 and 6 (pgs. 10-11 of spec). Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Claim Rejections - 35 USC § 112(b)
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 26 and 28 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.
Claim 26 recites “A method for producing a spinal cord motor neuron, comprising the steps according to the method of claim 8”, which is indefinite. Claim 26 is unclear because the body of the claim requires the steps according to claim 8, the preamble requires a method of producing a spinal cord motor neuron, however the steps according to claim 8 do not recite the formation of a spinal cord motor neuron, rather they recite the production of a culture spherical body (preamble). It is not clear if the preamble of claim 26 is reciting an inherent result of practicing the method of claim 8, wherein the spherical body of claim 8 contains a spinal cord motor neuron; or if additional steps are required to achieve the spinal cord motor neuron of claim 26.
Claim 28 recites “A method for producing a GABAergic neuron or its progenitor cell, comprising the steps according to the method of claim 8”, which is indefinite. Claim 28 is unclear because the body of the claim requires the steps according to claim 8, the preamble requires a method of producing a s GABAergic neuron or its progenitor cell, however the steps according to claim 8 do not recite the formation of a GABAergic neuron or its progenitor cell, rather they recite the production of a culture spherical body (preamble). It is not clear if the preamble of claim 28 is reciting an inherent result of practicing the method of claim 8, wherein the spherical body of claim 8 contains a GABAergic neuron or its progenitor cell; or if additional steps are required to achieve the GABAergic neuron or its progenitor cell of claim 28.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 26 and 28 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 26 recites “A method for producing a spinal cord motor neuron, comprising the steps according to the method of claim 8”. Additionally, claim 28 recites “A method for producing a GABAergic neuron or its progenitor cell, comprising the steps according to the method of claim 8”. Neither claim provides any additional limitations in the body of the claim other than referring to the method of claim 8. The preambles of claims 26 and 28 appear to recite the intended result of practicing the method of claim 8. If the claim uses the patent preamble only to state a purpose or intended use for the invention, then the preamble is not limiting (Bio-Rad Laboratories Inc. v. 10X Genomics Inc, 2020). Therefore, claims 26 and 28 fail to further limit claim 8.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 8-9, 11, 13, 26, and 28 are rejected under 35 U.S.C. 103 as being unpatentable over Nogueira et al (Journal of Biological Engineering, 2019), in view of Knoblich et al (US20150330970A1) and Kato et al (Unofficial Translation from Information Disclosure Statement and NPL reference provided by Applicant on 09/12/2023, “Development of 3D floating iPS cell differentiation induction culture device for industrial use”, 2018; also cited in WIPO Written Opinion mailed on 03/22/2022).
Claim interpretation: The specification defines “the term ‘unsteady’ means not unidirectional drive (operation)/motion (movement) of the stirring blade, but drive/motion with a variable speed/reciprocating motion/reverse motion”, therefore the claimed phrase “unsteadily operating the stirring blade” is interpreted to mean operating the stirring blade with variable speed, reciprocating motion, or reverse motion.
Claim 26 recites “A method for producing a spinal cord motor neuron, comprising the steps according to the method of claim 8”. Additionally, claim 28 recites “A method for producing a GABAergic neuron or its progenitor cell, comprising the steps according to the method of claim 8”. Neither claim provides any additional limitations in the body of the claim other than referring to the method of claim 8. The preambles of claims 26 and 28 appear to recite the intended result of practicing the method of claim 8. If the claim uses the patent preamble only to state a purpose or intended use for the invention, then the preamble is not limiting (Bio-Rad Laboratories Inc. v. 10X Genomics Inc, 2020). Therefore, Claims 26 and 28 are being interpreted to be met by the completion of the method of claim 8.
Regarding claim 8, Nogueira teaches a method of producing a spherical body (spheroid), comprising the steps of (a) placing pluripotent stem cells in a culture tank with a stirring blade (See Fig. 1 and description). Nogueira teaches the step (b) of operating the stirring blade to perform stirring culture of the pluripotent stem cells in the presence of a pluripotent stem cell maintenance medium within a culture apparatus which comprises an unconventional vertical wheel stirring apparatus (See Fig. 1 and description; pg. 2, col. 2, last para). Nogueira teaches that the pluripotent stem cells which have been cultured in the unconventional vertical wheel stirring apparatus are capable of differentiating into neural progenitor cells (pg. 7, Col. 1, last para).
Nogueria does not teach step (c) of claim 8 which requires performing stirring of the pluripotent stem cells in the presence of a neuronal differentiation medium. Nogueria does not teach that the neuronal differentiation medium contains retinoic acid as required by claim 13.
However, Knoblich teaches methods of performing 3D culture of organoids/spheroids which contain multiple cell types (abstract).
Regarding claims 8 and 13, Knoblich teaches the directed differentiation of human pluripotent stem cells in culture in a spinning bioreactor in differentiation media containing retinoic acid ([0070]). Additionally, Knoblich teaches at the stage where the spheroid culture is stirred or shaken in a bioreactor, the culture reaches an enlarged size which is dependent on constant nutrient supply, best achieved by flushing the cells through stirring or shaking ([0039]).
Knoblich teaches that the 3D spheroids comprise a heterogenous population of neuronal tissue cells ([0041]).
Regarding claim 11, Knoblich teaches the spheroids are introduced to the bioreactor on day 11 ([0070]) and allowed to differentiate until 20 days of differentiation ([0071]), which meets the alternative limitation of claim 11 requiring that step (c) of claim 8 be performed for at least 10 days.
One of ordinary skill in the art would find it obvious at the effective filling date of the instant invention to combine the method of pluripotent stem cell spheroid culture of Nogueria with the method of differentiating neural spheroids of Knoblich to arrive at the instant invention. One of ordinary skill in the art would be motivated to make this combination because Nogueria teaches that the cultured pluripotent stem cell spheroids are able to differentiate into neural cells and Knoblich teaches the directed differentiation of human pluripotent stem cells into neural spheroids. Additionally, one of ordinary skill in the art would be motivated to make the specific combination where the cells are differentiated within a stirred/shaken bioreactor environment because Knoblich teaches at the stage where the spheroid culture is stirred or shaken in a bioreactor, the culture reaches an enlarged size which is dependent on constant nutrient supply, best achieved by flushing the cells through stirring or shaking ([0039]). One of ordinary skill in the art would have a reasonable expectation of success when combining Nogueria with Knoblich because both teach similar embodiments of spheroid culture within bioreactors and therefore all the necessary information to make the combination successfully is taught.
Nogueria and Knoblich do not teach that the stirring of the bioreactor is “unsteadily” performed as required by steps (b) and (c) of claim 8. Nogueria and Knoblich do not teach that the unsteady operation step comprises an up-and-down reciprocating motion, a left-and-right reciprocating motion, a rotational motion with a variable speed, or a rotational reciprocating motion of the stirring blade, in the steps (b) and (c) as required by claim 9.
However, Kato discloses a bioreactor termed the “VMF reactor”.
Regarding claim 8, Kato discloses the VMF reactor with unsteady stirring using a vertical agitation device (described in translation on pg. 7, lines 27-28). Kato describes human iPS cell differentiation using the VFM reactor and further states that “Figure 16c shows neurons induced to differentiate from human iPS cells by the VMF reactor. Although an unprecedented differentiation efficiency was obtained, the details are omitted in this paper because the results should be introduced by researches on another occasion” (stated in translation, pg. 9, last para spanning pg. 10).
Regarding claim 9, the VMF reactor is described to employ vertical or up-down reciprocating motion of an elliptical blade (described in translation on pg. 7, paras 1-2).
Regarding claims 26 and 28, the claims require the method of claim 8 be completed which is taught by the combination of Nogueria, Knoblich, and Kato (see claim interpretation at beginning of rejection).
One of ordinary skill in the art would find it obvious at the effective filling date of the instant invention to combine the method of pluripotent stem cell differentiation into neural lineage cells employing a bioreactor taught by Nogueria and Knoblich with the VMF bioreactor taught by Kato to arrive at the instant invention. One of ordinary skill in the art would be motivated to make this combination because Nogueria teaches that the cultured pluripotent stem cell spheroids from the vertical wheel bioreactor are able to differentiate into neural cells and Knoblich teaches the directed differentiation of human pluripotent stem cells into neural spheroids employing stirring/shaking within a bioreactor. Additionally, one of ordinary skill in the art would be motivated to make the specific combination where the VMF reactor with unsteady stirring using a vertical agitation device is employed to culture pluripotent stem cells because Kato teaches that the bioreactor is able to differentiate iPS cells into neurons and states “an unprecedented differentiation efficiency was obtained” (stated in translation, pg. 9, last para spanning pg. 10). One of ordinary skill in the art would have a reasonable expectation of success when combining Nogueria and Knoblich with Kato because both teach similar embodiments of spheroid culture within bioreactors and therefore all the necessary information to make the combination successfully is taught. Additionally, Kato teaches that they were able to successfully culture and differentiate pluripotent stem cells into neurons using the bioreactor apparatus which is a demonstration of success.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CONSTANTINA E STAVROU whose telephone number is (571)272-9899. The examiner can normally be reached M-F 8:00-5:00.
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CONSTANTINA E. STAVROU
Examiner
Art Unit 1632
/PETER PARAS JR/Supervisory Patent Examiner, Art Unit 1632