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 .
Claim Status
Claims 1, 3-12, and 14-17 are currently pending in this application.
Election/Restrictions
Applicant’s election with traverse of Group I, claims 3-11, in the reply filed on Nov. 27, 2025 is acknowledged. Upon further consideration, the restriction requirement as set forth in the Office action mailed on Oct. 2, 2025 is hereby withdrawn. Claims 1, 3-12, and 14-17 have been considered on the merits and all arguments have been fully considered.
Claim Objections
Claims 1, 4-7, 11-12 and 14 are objected to because of the following informalities:
The amendments to claims 1, 4, 12 and 14 are nearly illegible due to scanning of a submission with colored text, i.e., colored MS Word tracked changes. See 37 CFR 1.52.
Claim 1 is objected to because where a claim sets forth a plurality of elements or steps, each element or step of the claim should be separated by a line indentation, 37 CFR 1.75(i). See MPEP §608.01(m).
Claims 1, 4-7, and 11 are objected to for numerous instances of a numeral followed by a unit (e.g., µM, µg/mL, ng/mL) without a blank space between them, such as in “10µM,” “5µM,” 5.5µg/mL, 55ng/mL, etc. Appropriate correction is required.
Claim Interpretation
In the claims, the term “chemical culture system” is interpreted as a single composition product comprising a defined mixture of the specifically recited components (e.g., medium and additives).
The term “culture medium” viewed in light of the specification has implied broad limitations to encompass any composition comprising capable of comprising a living cell, at least for a short duration (e.g., 1 millisecond) but may also comprise essential nutrients suitable for growth and/or proliferation of at least mammalian cell type. However the term “basic” regarding a culture medium is not defined by the claims or instant specification and, thus, is considered non-limiting beyond meaning the medium is generally suitable for use with many diverse cell types, such as by comprising minimum essential ingredients. For example, the basic culture medium need not comprises non-essential amino acids as noted as optional at instant pg. 5, ¶ 7.
The term “recombinant human transferrin” when viewed in light of the specification means a human transferrin protein obtained via genetic engineering, and having no relationship to a recombinant human.
In claim 1, the phrase “at least one of piperidinol oxide, luteolin” is interpreted as requiring either piperidinol oxide or luteolin but not necessarily both. Similarly, the limitation “at least one of D(+)-galactose, recombinant human transferrin” requires either D(+)-galactose or recombinant human transferrin but not necessarily both.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
The claimed inventions of claims 12 and 13-17 are each directed to non-statutory subject matter. The claim(s) does/do not fall within at least one of the four categories of patent eligible subject matter because these claims are directed to a “use” suggesting a process but no active step is recited and instead recites a limitation regarding a use(s). Therefore, it is not clear if these claims are directed to a product or a process.
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 1, 4-12, and 14-17 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 pre-AIA the applicant regards as the invention.
The claims are interpreted as provided in a previous section.
Claim 1 recites “at least one of piperidinol oxide, luteolin and at least one of D(+)-galactose, recombinant human transferrin”, which is ambiguous and unclear as to the precise scope of the additives claimed without proper grammar/punctuation. Claims 4-12, and 14-17 are included in this rejection.
Claim 4 recites a further limitation to the piperidinol dosage, but this is merely an optional component of the chemical culture system, and thus this claim is indefinite for any alternative option lacking the small molecular compound additive that is piperidinol.
Claim 5 recites a further limitation to the luteolin dosage, but this is merely an optional component of the chemical culture system, and thus this claim is indefinite for any alternative option lacking the small molecular compound additive that is luteolin.
Claim 6 recites a further limitation to the of D(+)-galactose dosage, but this is merely an optional component of the chemical culture system, and thus this claim is indefinite for any alternative option lacking the small molecular compound additive that is of D(+)-galactose.
Claim 7 recites a further limitation to the recombinant human transferrin dosage, but this is merely an optional component of the chemical culture system, and thus this claim is indefinite for any alternative option lacking the small molecular compound additive that is recombinant human transferrin.
Claim 8 recites the term “minimum essential medium non-essential amino acids”, which is not defined in the instant claims, the instant specification or the prior art. Although “minimum essential amino acids” and “nonessential amino acids” supplements are known to the skilled artisan, a person of ordinary of skill in the art would not understand the metes and bounds of “minimum essential medium non-essential amino acids.”
Claim 9 recites the term “growth factors,” which in view of dependent claims 10-11 encompasses vitamins and progesterone, which are not ordinarily categorized as growth factors in the art. If the applicant acts as her own lexicographer to redefine a term of a claim contrary to its ordinary meaning, the written description must clearly define the claim term and set forth the uncommon definition so as to put one reasonably skilled in the art on notice that the applicant intended to so redefine that claim term. Process Control Corp. v. HydReclaim Corp., 190 F.3d 1350, 1357, 52 USPQ2d 1029, 1033 (Fed. Cir. 1999). In the instant case, there is no such clear redefinition, and, thus, the term “growth factor” as used in the claims is indefinite. Claims 10-11 are included in this rejection for depending from indefinite claim 9.
Claim 11 recites a small molecule “is” immediately followed by a value fused with a unit of concentration, which is incoherent, ambiguous and unclear as to how each molecule “is” a concentration.
Claim 16 recites “the DRG neuron differentiation and culture process,” which lacks proper antecedent basis within claim 16 or a claim from which it depends from, either directly or indirectly.
Claim 17 recites “the cortical neuron differentiation culture process,” which lacks proper antecedent basis within claim 17 or a claim from which it depends from, either directly or indirectly.
Claims 12 and 14-17 are each directed to a “use” suggesting a process but no active step is recited and instead recites a limitation regarding a use(s). Therefore, it is not clear if these claims are directed to a product or a process. Claim 12 recites “the induction of pluripotent stem cells to neural stem cells or the induction of brain organoids,” which is incoherent, ambiguous and unclear as to whether this is an intended use or a process comprising an active step. Therefore, these claims were not further examined on the merits.
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 12-17 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 12 further recites only an intended use of the chemical culture system product of claim 1.
Claim 14 further recites only an intended use for the chemical culture system of claim 1. As the intended use language of use “in inducing neural directed differentiation of stem cell and differentiated cell culture” implies no structural limitation to the system of claim 1, claim 14 fails to limit the scope of claim 1. Similarly, claims 15-17 further limit the intended use of claim 14 without reciting or implying any additional limitation to the system of claim 1.
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
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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 1, 6, and 9-10 are rejected under 35 U.S.C. 103 as being unpatentable over Lu (CN106244548A, IDS ref.) in view of Yan (CN104694475A, IDS ref.).
The claims are interpreted as provided in a previous section.
Lu teaches a cell culture medium comprising a medium (e.g., DMEM or DMEM/F12,) and the additive luteolin at an amount of 35 µM (preferably 10 µg/mL) (pg. 2, last para., to pg. 3; claim 7). Lu teaches using such a medium for inducing stem cells into neural progenitor cells and differentiated neural cells.
Lu does not expressly teach the medium comprises D-galactose at an amount of 5-25 µg/mL
However Yan teaches a neural stem cell medium comprising D(+)-galactose as an additive at 7.5 µg/mL and DMEM with DMEM/F12 as the base/basic culture medium ([0046]; [0051]; Abstract; ([0013], [0003], [0052]-[0054]; claims 1 and 3).
It would have been prima facie obvious to one of ordinary skill in the art before the earliest effective time of filing to combine into a single medium the additive luteolin taught by Lu and the additive D(+)-galactose taught by Yan at the concentrations taught by each for culturing neural stem cells and/or differentiating stem cells into neural cells in cultures. One of ordinary skill in the art with the goal of making neural cells from stem cells would be motived by each of Lu and Yan to include the respective additive at already validated concentrations.
Regarding claim 6, Yan teaches wherein the galactose is at 7.5 µg/mL (Abstract).
Regarding claims 9-10, Yan teaches wherein the medium additives include growth factors (e.g., epidermal growth factor, bFGF, progesterone, insulin, and/or putrescine) and inorganic salts (iron and sodium selenite), such as for use in culturing neural stem cells ([0015]; [0020]; [0035]; [0055]; [0005]; claims 1 and 3).
Claims 1, 5-6, and 9-10 are rejected under 35 U.S.C. 103 as being unpatentable over Lu in view of Yan as applied above, and further in view of Arora (Arora, M., Mater methods 3(175): 24 (2013)).
Regarding claim 5, although Lu and Yan teaches including the additive luteolin at 35 µM, the combination of Lu and Yan does not teach wherein luteolin is present at 10 or 50 µM.
However Arora teaches cell culture media can be optimized for specific concentrations of components using routine experimentation (pg. 7, last para.).
It would have been prima facie obvious to one of ordinary skill in the art at the effective time of filing to modify a medium taught by Lu and Yan by further optimizing the luteolin concentration for use in inducing stem cells toward neural differentiation as taught by Lu. One of ordinary skill in the art would be motivated to do so because Lu teaches the purpose of adding luteolin is to improve neural differentiation as a results-effective variable and it can be optimized using routine experimentation within the skills of one of ordinary skill in the art as taught by Arora to arrive at concentration of either 10 or 50 µM, such as starting from dosage of 35 µM. One of ordinary skill in the art would be motivated to do so to improve differentiation efficiency and obtain more neural-differentiated cells as is the goal of Lu. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). It is routine procedure to optimize component amounts to arrive at an optimal product that is superior for its intended use, since it has been held where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are close enough that one skilled in the art would have expected them to have the same properties. See M.P.E.P. §2144.05(I).
Claims 1, 6, and 8-10 are rejected under 35 U.S.C. 103 as being unpatentable over Lu in view of Yan as applied above, and further in view of Choi (Choi et al., Korean Journal of Chemical Engineering 24: 1058-63 (2007)).
Regarding claim 8, Lu teaches wherein the foundation of the cell culture medium is DMEM (pg. 3, para. 1-2); however, the combination of Lu and Yan does not expressly teach wherein the medium comprises “minimum essential medium non-essential amino acids.”
Choi teaches a medium for culturing and differentiating stem cells based on DMEM and supplemented with essential amino acids (EAs), non-essential amino acids (NEAs), or both (IMDM) (pg. 1059, left col., last para., to right col., 1st para.; Table 1). Further, Choi teaches exogenously added amino acids affect mammalian cells in culture, often beneficially, and can alter proliferation and differentiation rates with EAs but not NEAs preferred for both (pg. 1058, left col., last para., to right col., 3rd para.; abstract).
It would have been prima facie obvious to one of ordinary skill in the art before the earliest effective time of filing with the goal of making a medium for stem cell culture to add essential and/or non-essential amino acids to a medium based on DMEM . One of ordinary skill in the art would be motivated by Choi demonstrating media for proliferating stem cells using these components, such as for proliferation and/or differentiation.
Claims 1, 4, and 9-10 are rejected under 35 U.S.C. 103 as being unpatentable over Yan (CN104694475A, IDS ref.) in view of Zhang (Zhang et al., Free Radic Biol Med 24: 66-75 (1998)).
Yan teaches a neural stem cell medium comprising D(+)-galactose as an additive at 7.5 µg/mL and DMEM with DMEM/F12 as the base/basic culture medium ([0046]; [0051]; Abstract; ([0013], [0003], [0052]-[0054]; claims 1 and 3).
Regarding claims 1 and 4, Yan does not teach wherein the medium comprises a piperidinol oxide at a concentration of 10-200 µM. However Zhang teaches including in a cell culture medium the additive piperidinol oxide (TPL-H, 4-OH-2,2,6,6-tetramethyl-1-hydroxypiperidine) at 20 µM to act as an antioxidant to protect cells from oxidative stress and injury (Fig. 5, pg. 66, right col., last para.). Thus, it would have been prima facie obvious to one of ordinary skill in the art at the effective time of filing to modify a medium taught by Yan by including the piperidinol oxide TPL-H at 20 as taught by Zhang. One of ordinary skill in the art would be motivated to protect the cells from oxidative damage to help maintain optimal viability.
Regarding claims 9-10, Yan teaches wherein the medium additives include growth factors (e.g., epidermal growth factor, bFGF, progesterone, insulin, and/or putrescine) and inorganic salts (iron and sodium selenite), such as for use in culturing neural stem cells ([0015]; [0020]; [0035]; [0055]; [0005]; claims 1 and 3). Thus, the claimed invention as a whole is prima facie obvious to one of ordinary skill in the art before the effective time of filing in the absence of evidence to the contrary.
Allowable Subject Matter
Claims 3 and 7 are objected above and also here as being dependent upon a rejected base claim, however these claims appear to be directed to allowable subject matter if both the informalities noted above are overcome and if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
The reasons for indicating allowable subject matter of claim 3 is a search of the prior arts does not reveal any disclosures that teaches or reasonably suggests a cell culture medium comprising piperidinol oxide at 10-200 µM and recombinant human transferrin at 50-200 ng/mL.
The reasons for indicating allowable subject matter of claim 7 are a search of the prior arts does not reveal any disclosures that teaches or reasonably suggests a cell culture medium comprising recombinant human transferrin at a concentration of 200 ng/mL or less.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERIC J ROGERS whose telephone number is (571)272-8338. The examiner can normally be reached Monday - Friday 9:00-6:00.
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/ERIC J ROGERS/Examiner, Art Unit 1638
/KEVIN K HILL/Primary Examiner, Art Unit 1638