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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 31st, October, 2025 has been entered.
Claim Status
Claims 1, 7-21 and 23-25 are pending.
Claims 11-19 are withdrawn.
Claims 1, 7-10, 20-21 and 23-25 are under examination.
New Claim Rejections - 35 USC § 112 (a)
Written Description
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.
Claim 23 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
In the amendment filed on 31st, October, 2025, new claim 23 was added and recites the limitation “the neuroectoderm marker-positive cell aggregate is not encapsulated.” This new limitation appears to be new matter. A review of the originally filed specification by the Examiner did NOT find any specific basis for the recited limitation. The disclosure (including the specification, claims and sequence listing) as originally filed, does not contain an explicit recitation of the limitation. The closest support for the new limitation are statements regarding prior art insertion of aggregates into trademarked Matrigel® (“a gel-like Matrigel particle is easily broken at the time of insertion” para. [0015]), the statement of “to insert the above-mentioned cell aggregate” (para. [0015]) which also appears to refer to insertion into Matrigel® specifically, and a statement of “a step of culturing a neuroectoderm marker-positive cell aggregate in the first medium containing the extracellular matrix with a concentration of more than 10% by volume in a dispersed state without inserting into the extracellular matrix” (para. [0074]). The closest support is the aforementioned paragraph 74, but this does not provide sufficient support because the newly added limitation recites “the neuroectoderm marker-positive cell aggregate is not encapsulated.” The term “encapsulated” includes being encapsulated by all possible encapsulating substances and therefore is not commensurate in scope with the disclosed “without inserting into the extracellular matrix” (para. [0074]) which at most appears to exclude encapsulation in the extracellular matrix. Because the new limitation is broader than the support found in the specification, and there is not information in the specification to lead one of ordinary skill to these broader embodiments, the support is not sufficient.
Furthermore, the new limitation recites a negative limitation “not encapsulated.” Applicant is directed to MPEP section 2173.05(i) which states any negative limitation or exclusionary proviso must have basis in the original disclosure. As stated above, this negative limitation was not found to have basis in the original disclosure.
As noted by MPEP 608.04(a), new matter includes not only the addition of wholly unsupported subject matter, but may also include adding specific percentages or compounds after a broader original disclosure, or even the omission of a step from a method. In the instant case one skilled in the art would NOT consider the limitation to be explicitly, implicitly, or inherently supported by Applicant’s disclosure.
Hence, there is insufficient written descriptions support for the instantly claimed limitation of and Applicant has not shown possession of the invention.
Response to Arguments
Applicant’s arguments, filed 31st, October, 2025, have been fully considered but are not found persuasive.
Applicant argues support for newly added claim 23 could be found in [0074], page 29, in [0015], pages 10-11 and Experimental Example 3 (para. [0119]) (pg. 6-7). Applicant argues “the present specification clearly explains mixing the first medium and the extracellular matrix component on ice such that the extracellular matrix component is dispersed in the solution (opposite to inserting/encapsulating the aggregates into a gel-like an extracellular matrix component particles/droplets) and further explains that the neuroectoderm marker-positive cell aggregate is not inserted/encapsulated into a gel-like extracellular matrix component particle” (pg. 7 4th para.).
In response, as discussed above, these provide support for the aggregate not being encapsulated by the extracellular matrix component, but do not provide support for the full breadth of newly added claim 23 because the claim recites “the neuroectoderm marker-positive cell aggregate is not encapsulated” which encompasses a lack of encapsulation by all possible encapsulation methods. Because this is a negative limitation, it requires basis in the original disclosure (MPEP section 2173.05(i)). While the original disclosure has basis for encapsulation by Matrigel® or the Extracellular Matrix component, or lack thereof, it does not have basis for the full breadth of encapsulation by all possible encapsulation methods or the lack of encapsulation by all possible encapsulation methods.
New Claim Rejections - 35 USC § 112 (a)
Written Description
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 1, 7-10, 20-21 and 23-25 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The purpose of the written description requirement is to ‘ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor’s contribution to the field of art as described in the patent specification.” Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1353-54 (Fed. Cir. 2010) (en banc) (quoting Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920 (Fed. Cir. 2004)). To satisfy the written description requirement, the specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991). See also MPEP 2163.04.
For a claim to a genus, a generic statement that defines a genus of substances by only their functional activity does not provide an adequate written description of the genus. Reagents of the University of California v. Eli Lilly, 43 USPQ2d 1398 (CAFC 1997).
To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include a disclosure of a representative number of species to describe the complete structure of the claimed genus and/or disclosure of a complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, and any combination thereof.
Scope of the Claims
Instant claims encompass:
“preparing a solution comprising a first medium and an extracellular matrix component by mixing the first medium and the extracellular matrix component on ice such that the extracellular matrix component is dispersed in the solution at a concentration of from 20% to 50% by volume” and “suspension culturing a neuroectoderm marker-positive cell aggregate in the solution” (claim 1 and dependents)
These solutions encompass all possible medias with all possible extracellular matrix components dispersed in the solution at a concentration of from 20% to 50%. Importantly, because the claim requires “suspension culturing a neuroectoderm marker-positive cell aggregate in the solution” the solution must be capable of being used in suspension culture. In other words, the solution appears to require a liquid solution for suspension culture and not a gel or solid-like particle.
“a second medium containing 0.5% by volume or less of an extracellular matrix component” which includes all possible medias with all possible extracellular matrix components of 0.5% by volume or less. Importantly, dependent claim 7 requires the culturing in the second medium is performed by suspension culture and therefore the second medium must be suitable for suspension culture.
Disclosure of Structure and Disclosure of Species
Solutions with mediums and Extracellular Matrix Components
Regarding the solutions comprising a first medium and extracellular matrix components, Applicant discloses two culture medium formulation that are suitable for suspension culture and otherwise meet claim limitations, each with Matrigel® as the “extracellular matrix component.” The two solutions are described to have Matrigel® as 30% or 50% by volume (para. [0120]) respectively.
Second Medium
Regarding the culture mediums containing 0.5% by volume or less of an extracellular matrix component, the specification describes suitable mediums (para. [0096]). Regarding suspension culture, the specification describes “medium not containing an extracellular matrix was used.” (para. [0133]). Therefore, no mediums between 0.5% and 0% extracellular matrix appear to be described for suspension culture.
Structure/Function Correlation
Solutions with mediums and Extracellular Matrix Components
Regarding the solutions for suspension culture where “the extracellular matrix component is dispersed in the solution at a concentration of from 20% to 50% by volume,” Applicant is first directed to the art of record of Corning (The Ultimate Guide to Corning® Matrigel® Matrix, 2017; Accessed at: https://www.corning.com/media/worldwide/cls/documents/CLS-DL-AC-016-web.pdf) As set forth previously, the art of Corning, the manufacturer of Matrigel®, evidences Matrigel® is prepared by mixing it with a medium on ice such that the Matrigel® is dispersed in the solution ( “Keep Matrigel matrix on ice at all times during handling” and “Dilute Matrigel matrix by adding it to an ice-cold solution” pg. 5 “Do this”) and accordingly, Matrigel® is normally prepared similar to the solution of instant claims. Applicant is additionally directed to the art of Corning2 (2024, accessed at: https://www.corning.com/catalog/cls/documents/faqs/CLS-DL-CC-026.pdf) which evidences Matrigel® “is approximately 60% laminin, 30% collagen IV, and 8% entactin” (pg. 1 “What is Corning Matrigel matrix?”). Corning2 further evidences Corning Matrigel® matrix diluted to a concentration of 3 mg/mL will form a gel (pg. 5 “What is the lowest concentration of Corning Matrigel matrix that will form a gel?”). Therefore, at full concentration, Matrigel®, which is not a liquid, would have 60% of an ECM component laminin, 30% of an ECM component collagen IV, and 8% of an ECM component entactin which has extracellular matrix components dispersed in the solution at a concentration outside the range (60% or 8%) as well as inside the range. Furthermore, Matrigel® is diluted to a final concentration of 3 mg/mL which is 0.3 g/mL or 0.3% and this arrives at a concentration of have 18% of an ECM component laminin, 9% of an ECM component collagen IV, and 4.8% of an ECM component entactin which would be well below the claimed “20% by volume to 50%” and would still be a gel which is not suitable for suspension culture.
Therefore, because the structure/function relationship indicates that many solutions with an extracellular matrix component dispersed in the solution at a concentration of from 20% by volume to 50% are gels or gel-like particles (Matrigel® gel-like particle or Matrigel® Gel), which are not suitable for suspension culture, and because Applicant has not provided sufficient detail to lead one of ordinary skill to which mediums with which ECM components at which amounts would arrive at a medium suitable for suspension culture, the solutions have not been described in sufficient detail, and Applicant has not shown possession of the claimed invention.
Second Medium
Regarding the second medium containing 0.5% by volume or less of an extracellular matrix component it is noted, that as discussed above, Matrigel® diluted to a final working concentration of 3 mg/mL has 4.8% of an ECM component entactin which falls within claimed limitations of “0.5% by volume or less of an extracellular matrix component” but is not suitable for the required suspension culture because it is a gel, as discussed above.
Written Description – Conclusion
Therefore, the examiner concludes there is insufficient written description support for the instantly claimed genera. Specifically, there is insufficient description of solutions comprising a first medium and an extracellular matrix component where the extracellular matrix component is dispersed in the solution at a concentration of from 20% to 50% by volume” that are liquid and can be suspension cultured as claimed. Furthermore, it is noted that the two solutions described are merely described as 30% or 50% by volume (para. [0120]) of Matrigel® respectively, which also does not provide sufficient description because, as discussed above, as discussed above, Matrigel® as 30% or 50% by volume appears to be a gel (see Structure/Function Correlation above). It appears that the two described solutions that are suitable for suspension culturing might be 30% or 50% by volume of working dilution of Matrigel®. Regarding the solutions with first medium and an extracellular matrix component from 20% by volume to 50% by volume, there is insufficient description of these solutions. The specification merely describes two specific examples of solutions with specific concentrations, which is not representative of the full breath of solutions with a first medium and an extracellular matrix component where the extracellular matrix component is dispersed in the solution at a concentration of from 20% to 50% by volume that are suitable for suspension culture, which encompasses numerous solutions.
Regarding the second medium containing 0.5% by volume or less of an extracellular matrix component, the specification merely describes mediums with no extracellular matrix component and no mediums are described with between 0.5% by volume and 0% by volume of an extracellular matrix component that are suitable for suspension culturing.
The state of the art evidences solutions with concentrations of an extracellular matrix component inside and outside the range for both mediums that are gels and therefore cannot be used in the suspension culture require by instant claims. The instant specification fails to provide a nexus for the formulation of the solutions/mediums and their required function as suitable for suspension culture. This lack of nexus is not remedied by the state of the art. Thus, in the face of an unpredictable art, one of ordinary skill in the art could not envision the requisite structural elements and the elements that could be modified from the disclosures of the application or art at the time of filing.
Examiner’s Remark
Regarding the culture mediums with extracellular matrix components, as stated above Applicant discloses two culture medium formulation that are suitable for suspension culture and otherwise meet claim limitations, each with Matrigel® as the “extracellular matrix component.” The two solutions are described to have Matrigel® as 30% or 50% by volume (para. [0120]) respectively. Applicant discloses suspension culturing with these mediums. However, as discussed above, Matrigel® as 30% or 50% by volume appears to be a gel (see Structure/Function Correlation above). Therefore, it appears that the 30% or 50% by volume of Matrigel® of the examples may be 30% or 50% by volume of the working dilution of Matrigel®.
Examiner’s Remark
The Examiner notes that Matrigel® is a trademark and is not allowed in claims (see MPEP 2173.05(u)).
New 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.
Claim 24 is 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 24 recites “at the start of the suspension culturing the solution contained 2 x 104 cells per well, in 100 μL” which appears to refer to single cells in suspension in a well, while claim 1, upon which claim 24 depends, recites suspension culturing a neuroectoderm marker-positive cell aggregate. Therefore, because claim 24 does not refer to an aggregate, there is no nexus between the scope of claim 24 and the method recited in claim 1, upon which it depends, and it is unclear what the metes and bounds of claim 24 encompass.
Withdrawn Claim Rejections - 35 USC § 102
The rejection of claims 3-4, 6 and 22 under 35 U.S.C. 102(a)(1) as being anticipated by Bolognin et al. (WO-2017/060884-A1; see IDS filed 12th, May, 2021; henceforth “Bolognin ”) as evidenced by Corning (The Ultimate Guide to Corning® Matrigel® Matrix, 2017; Accessed at: https://www.corning.com/media/worldwide/cls/documents/CLS-DL-AC-016-web.pdf) and Kosik et al. (J Neurosci. 1987 Oct;7(10):3142-53.; henceforth “Kosik”) as set forth in the previous office action are withdrawn in view of the cancellation of these claims.
The rejection of 1, 7, 9-10 and 20-21 under 35 U.S.C. 102(a)(1) as being anticipated by Bolognin et al. (WO-2017/060884-A1; see IDS filed 12th, May, 2021; henceforth “Bolognin ”) as evidenced by Corning (The Ultimate Guide to Corning® Matrigel® Matrix, 2017; Accessed at: https://www.corning.com/media/worldwide/cls/documents/CLS-DL-AC-016-web.pdf) and Kosik et al. (J Neurosci. 1987 Oct;7(10):3142-53.; henceforth “Kosik”) as set forth in the previous office action are withdrawn in view of Applicant’s amendments and Applicant’s arguments of record that placing the aggregates in Matrigel® of Bolognin is not suspension culturing (pg. 12).
Withdrawn Claim Rejections - 35 USC § 103
The rejection of claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Bolognin et al. (WO-2017/060884-A1; see IDS filed 12th, May, 2021; henceforth “Bolognin”) as evidenced by Corning (The Ultimate Guide to Corning® Matrigel® Matrix, 2017; Accessed at: https://www.corning.com/media/worldwide/cls/documents/CLS-DL-AC-016-web.pdf) as applied to claims 1 and 6 above, in view of Gao et al. (Sci Rep. 2016 Jul 20:6:29944.; henceforth “Gao”) as set forth in the previous office action is withdrawn in view of Applicant’s amendments and Applicant’s arguments of record that placing the aggregates in Matrigel® of Bolognin is not suspension culturing (pg. 12).
Conclusion
No claim is allowable.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRIANA N EBBINGHAUS whose telephone number is (703)756-4548. The examiner can normally be reached M-F 9:30 AM to 5:30 PM ET.
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/BRIANA N EBBINGHAUS/Examiner, Art Unit 1632 /VALARIE E BERTOGLIO/Primary Examiner, Art Unit 1632