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 .
Claim Status
In the amendment filed 8th, June, 2026, Applicant cancelled claims 3-4 and added new claim 59.
Claims 1-2, 5, 14-15, 17, 19, 21-22, 25, 31 and 55-59 are pending.
Claim 31 is withdrawn.
Claims 1-2, 5, 14-15, 17, 19, 21-22, 25, and 55-59 are under examination.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 8th, June, 2026 has been entered.
Withdrawn Objections to Specification
Browser-Executable Code
The objection to the specification because it contained an embedded hyperlink and/or other form of browser-executable code as set forth in the previous office action is withdrawn in view of Applicant’s amendments.
Withdrawn Claim Objections
The objection to claim 57 because of informalities as set forth in the previous office action is withdrawn in view of Applicant’s amendments.
Withdrawn Claim Rejections - 35 USC § 112(a)
Written Description
The rejection of claims 1-2, 5, 14-15, 17, 19, 21-22, 25 and 55-58 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paragraph, as failing to comply with the written description requirement as set forth in the previous office action is withdrawn in view of Applicant’s amendments.
Moot Claim Rejections - 35 USC § 112(a)
Written Description
The rejection of claims 3-4 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 as set forth in the previous office action is moot in view of the cancellation of these claims.
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 19 remains 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 Invention
In the instant case, the genera are:
retinoic acid analogues (claim 19)
The broadest reasonable interpretation of the scope of this genus encompasses all possible “analogues” of retinoic acid signaling pathways.
The plain and ordinary meaning of an analogue is a structure that is similar to another and may have some overlapping properties. Therefore, the breadth of this genus encompasses structures that are similar to retinoic acid which includes structurally and functionally distinct members. Because the analogues may not retain all possible functions, this includes structurally and functionally distinct members that may or may not function to activate retinoic acid signaling as claimed (required by claim 1, upon which claim 19 depends).
Disclosure of Structure and Disclosure of Species
Activators of Retinoic Acid Signaling
Regarding the analogues of retinoic acid, Applicant discloses the following 20 species structures:
Retinoic acid, particularly 9-cis-retinoic acid (9cRA), 13-cis-retinoic acid (13cRA), and all-trans-retinoic acid (ATRA) (pg. 7).
Retinoic acid, all-trans retinoic acid; AM 580; TTNPB; Ch 55;CD437; BMS961;BMS 753; AM 80; CD 2314; AC 261066; AC 55649; CD 1530;Adapalene; Tazarotenic Acid; Tazarotene; EC 19; EC23 (pg. 31).
Structure/Function Relationship
Regarding the analogues of retinoic acid, as stated above (see scope of the Invention above), this encompasses distinct structures that have distinct functions mechanisms of action for the reasons stated above.
Regarding the analogues, Applicant is directed to the art of Klein et al. (J Biol Chem. 1996 Sep 13;271(37):22692-6.; henceforth “Klein”). Klein evidences neutral antagonists AGN 192870 and 193840 (pg. 22694) and inverse antagonists AGN 193109 (Figure 2) of Retinoic Acid Receptors (see also Table 1). Klein evidences inverse agonists are ligands that are capable of repressing basal receptor activity in the absence of an agonist (abstract) and Klein evidences neutral antagonists do not affect the receptor equilibrium but are capable of competitive antagonism of both agonists and inverse agonists (pg. 22692). Therefore, the art of Klein evidences analogues of retinoic acid include neutral antagonists, which would not activate retinoic acid receptors, and inverse antagonists, which would repress the retinoic acid receptors, and these fall outside of the functional requirements of instant claims because instant claim 1 recites a requirement of activating retinoic acid signalling. Therefore, because the art evidences the structure/function relationship is not predictable because analogues of retinoic acid do not predictably exhibit the required function of activating a retinoic acid receptor, and Applicant has failed to provide a nexus to lead one of ordinary skill to which analogues meet the required function, one of ordinary skill would not be able to envision the requisite structural elements at the time of filing.
Written Description - Conclusion
Therefore, the examiner concludes there is insufficient written description support for the instantly claimed genera. Specifically, there is insufficient description of retinoic acid analogues. The specification merely describes 20 specific species of retinoic acid signaling pathway activators or analogues. 20 species does not represent the large genus of structurally and functionally diverse species of retinoic acid analogues encompassed by Applicant’s claim.
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.
Response to Arguments
Applicant’s arguments, filed 8th, June, 2026, have been fully considered but are not found persuasive.
Applicant argues “Applicant has amended claim 19 to delete recitation of "or a functional
analogue or isomer thereof." Thus, amended claim 19 is supported by the specification and
overcomes the current rejection.” (pg. 9).
In response, the amended claims still includes the limitation of “a retinoic acid analogue” which has a written description issue for the reasons set forth in the grounds of rejection above.
Moot Claim Rejections - 35 USC § 112(a)
Scope of Enablement
The rejection of claim 4 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification did not enable the full scope of the claims is moot in view of the cancellation of this claim.
Examiner’s Remark
In view of Applicant’s argument that “Ashton fails to teach the claimed limitation of "wherein the ventral midbrain dopaminergic progenitor cells express forkhead box protein A2 (FOXA2) and LIM homeobox transcription factor 1 alpha (LMX1A)." Nowhere in Ashton is there any teaching of FOXA2 or LMX1A and all of the data and support in Ashton teaches a different cell population is produced, specifically, Nkx6.1 +/Olig2+ spinal motor neuron progenitors” (pg. 11), a new grounds of rejection under 35 USC § 112(a) because the full scope of the amended claims is not enabled is applied below.
New Claim Rejections - 35 USC § 112(a)
Scope of Enablement
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 1-2, 5, 14-15, 17, 19, 21-22, 25, and 55-59 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
A method for differentiating pluripotent stem cells into ventral midbrain dopaminergic progenitor cells, the method comprising
contacting a plurality of pluripotent stem cells with at least one inhibitor of TGFβ/Activin-Nodal signaling and at least one inhibitor of bone morphogenetic protein (BMP) signaling from day 0 to day 7;
contacting the plurality of pluripotent stem cells with ATRA at a concentration of 200-400 nM from day 0 to day 2; contacting the plurality of pluripotent stem cells with 500 nM 9-cis RA, 13-cis RA or tazarotenic acid (TA) from day 0 to day 2; or contacting the plurality of pluripotent stem cells with EC23 at a concentration of 10-20 nM of from day 0 to day 1; and
contacting the plurality of pluripotent stem cells with SAG 1.3 at a concentration of 50 nM or more from day 0 to day 9;
wherein the ventral midbrain dopaminergic progenitor cells express forkhead box protein A2 (FOXA2) and LIM homeobox transcription factor 1 alpha (LMX1A) (instant claim 1 and dependents).
And to obtain a cell population comprising at least 50%, at least 60%, at least 70%, or at least 80% ventral midbrain dopaminergic progenitor cells at least after 7 days after first contacting said plurality of stem cells with the at least one activator of Retinoic Acid (RA) signalling (instant claim 5).
does not reasonably provide enablement for:
all other culture conditions including but not necessarily limited to all possible timings, durations, concentrations of all possible
all other concentrations, timings, and durations of retinoic acid signaling activators that increase activation of a retinoic acid receptor
to arrive at the claimed and required functional result of the ventral midbrain dopaminergic progenitor cells express forkhead box protein A2 (FOXA2) and LIM homeobox transcription factor 1 alpha (LMX1A) (instant claim 1 and dependents).
and to arrive at the claimed and required functional result of the cell population comprises at least 50%, at least 60%, at least 70%, or at least 80% ventral midbrain dopaminergic progenitor cells at least after 7 days after first contacting said plurality of stem cells with the at least one activator of Retinoic Acid (RA) signalling (instant claim 5).
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the method of the invention commensurate in scope with these claims.
Wands Factors
The factors to be considered in determining whether undue experimentation is required are summarized In re Wands 858 F.2d 731, 8 USPQ2nd 1400 (Fed. Cir, 1988). The Court in Wands states: “Enablement is not precluded by the necessity for some 'experimentation.'” Clearly, enablement of a claimed invention cannot be predicated on the basis of quantity of experimentation required to make or use the invention. “Whether undue experimentation is needed is not a single simple factual determination, but rather is a conclusion reached by weighing many factual considerations.” (Wands, 8 USPQ2d 1404). The factors to be considered in determining whether undue experimentation is required include: (1) the quantity of experimentation necessary, (2) the amount or direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims. While all of these factors are considered, a sufficient amount for a prima facie case is discussed below.
Breadth of the Claims
Instant claims encompass methods for differentiating stem cells into ventral midbrain
dopaminergic progenitor cells comprising contacting a plurality of stem cells with “an effective amount of at least one activator of retinoic acid (RA) signaling” that increases activation of a retinoic acid receptor
This encompasses:
all possible “activators of retinoic acid (RA) signaling” that increase activation of a retinoic acid receptor including but not necessarily limited to nucleic acids, proteins or small molecules and further encompasses all possible timings and durations of each of these within the 1-4 days duration of the claim.
Importantly, instant claims require the functional result of “the ventral midbrain dopaminergic progenitor cells express forkhead box protein A2 (FOXA2) and LIM homeobox transcription factor 1 alpha (LMX1A)” (instant claim 1 and dependents),
And the functional result of the cell population comprises at least 50%, at least 60%, at least 70%, or at least 80% ventral midbrain dopaminergic progenitor cells at least after 7 days after first contacting said plurality of stem cells with the at least one activator of Retinoic Acid (RA) signalling (instant claim 5).
Direction or Guidance Presented
While contemplating all possible “activators of retinoic acid (RA) signaling” that increase activation of a retinoic acid receptor as part of a method to cause differentiation of the stem
cells into a cell population comprising ventral midbrain dopaminergic progenitor cells, Applicant provides limited guidance on culture conditions that result in the claimed cell types (Example 1; Figure 1).
Present Working Examples
The elements of the present working examples considered pertinent to the instant scope of enablement issues are summarized below.
Example 1 (pg. 59-75)
Stem cells: human embryonic stem cells (hESCs) which are a type of pluripotent stem cells
activator of retinoic acid (RA) signaling: all-trans RA
Concentration: 200 nM
Timings: all-trans RA was applied the first 1, 2, 3 or 4 days of differentiation (RA1D, RA2D, RA3D, RA4D) (Fig. 1a)
Additional conditions: dSMADi treatment was included in all experiments (pg.62). This appears to be for a timeframe of 7 days and appears to overlap with all-trans RA treatment (see Figure 1a which is copied below).
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Results: in hPSC-cultures not exposed to RA (RAOD), NSCs acquired a FOXG1+/OTX2+/HOXA2-FB-like identity (Fig. 1h)
A similar FB-like character was observed in RA1D cultures, though the number of FOXG1+ cells was somewhat reduced (Fig. 1h; Figure 7d (Supplementary Fig. 1d)).
In RA2D cultures, FB markers were suppressed and NSCs instead expressed a FOXG1-/OTX2+/HOXA2- MB-like character (Fig. 1h; Figure 7d (Supplementary Fig. 1d)).
In RA3D and RA4D cultures, NSCs acquired a FOXG1-/OTX2-/HOXA2+/ HOXB4- rostral HB and FOXG1-/OTX2-/HOXA2+/HOXB4+ caudal HB identities, respectively (Fig. 1h).
The specification states “These data suggest that a 48-hour RA-pulse suppresses FB fate and imposes a MB-like identity to hPSC-derived NSCs (Fig. 1i).”
Next, SHH signaling was activated to impose a ventral identity to NSCs.
Conditions: cultures were treated with Smoothened agonist SAG25 between 0-9 DDC (see Figure 2 a; copied below)
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Results: At 9 DDC, NSCs generated in SAG-only or RA1D+SAG conditions expressed the FB- specific markers FOXG1, SIX3, SIX6, and LHX2 (Fig. 2b) and the ventral marker NKX2.1 (Fig. 2a, b) which is a selective marker for the ventral telencephalon and diencephalon.
In RA2D+SAG cultures, FB markers were suppressed and NSCs adopted a LMX1A+/LMX1B+/FOXA2+/OTX2+ identity characteristic of vMB mDA neuron progenitors (Fig. 2a,b,d).
In RA3D+SAG or RA4D+SAG cultures, cells expressed HOX genes and the ventral markers NKX2.2, PHOX2B, NKX6.1, and NKX6.2 typical of cranial motor neuron (MN) progenitors of the HB28 (Fig. 2a, b, d; and data not shown).
Applicant states these data show: first, that increases in the duration of RA exposure imposes progressively more caudal regional brain identities (FB->MB->HB) of hPSC-derived NSCs (Fig. 1i), and
second, when combined with activation of the SHH pathway, treatment with RA for 48h appears sufficient to impose a LMX1A+/FOXA2+/OTX2+ vMB-like identity to NSCs (Figure 8e (Supplementary Fig. 2e)).
Applicant states Effective induction of a vMB NSC identity required the 48 hour RA-pulse to be initiated between 0-2 DDC (Figure 8b (Supplementary Fig. 2b)) and SAG treatment to start at 0 or 1 DDC at a concentration > 50 nM (Figure 8c,d (Supplementary Fig. 2c,d)).
Similar results were attained with two hESC-lines and two hiPSC-lines (Figure 8e (Supplementary Fig. 2e)).
To determine the sensitivity of the differentiation procedure to altered concentrations of RA, Applicants cultured cells in RA2D+SAG-conditions and altered the concentration of RA in the range of 100-800 nM and analyzed the identity of NSCs at 9 DDC. In cultures exposed to 200-400 nM RA, the vast majority of NSCs expressed a LMX1A+/NKX2.1- vMB-identity and few cells expressed a diencephalic LMX1A+/NKX2.1+ identity or NKX2.2 (Fig. 3a,c).
When RA concentration was reduced to 100 nM or increased to 800 nM RA, LMX1A+/NKX2.1- NSCs were generated but at lower numbers (Fig. 3c).
This indicates the required concentration range of all trans Retinoic acid is 200-400 nM when the majority of the population is required to be vMB.
Exposure of cells to 500 nM of 9-cis RA, 13-cis RA and the xenobiotic RA-analogue tazarotenic acid (TA) analogues for 48-hours mimicked the patterning activity of all-trans RA by imposing a LMX1A+/NKX2.1- vMB identity (Fig. 3h; Figure 9b (Supplementary Fig. 3b)),
EC23 could induce LMX1A*/NKX2.1- vMB cells, but this required a 20-fold reduction in concentration and treatment of cells only for 24 hours (Figure 9c (Supplementary Fig. 3c)).
Applicant states “Together, these data establish that the AP-patterning output in response to timed RA exposure is critically reliant on the RA concentration-dependent activation of CYP26A1 in responding hPSCs” (pg. 66).
Evidence of the Specification
Applicant is directed to Applicant’s own specification, which evidences specific concentrations, durations, components and timings that are required to obtain the claimed ventral midbrain dopaminergic progenitor cells.
Specific Activators of RA signaling
The instant specification evidences specific small molecules activators of retinoic acid signaling of all-trans RA, 9-cis RA, 13-cis RA and the xenobiotic RA-analogue tazarotenic acid (TA) analogues, and EC23 are required (Example 1).
Therefore, because the effects of different Specific Activators of RA signaling are not predictable, Applicant is not enabled for all activators of RA signaling that activate a retinoic acid receptor.
Specific Timings and Durations of Activators of RA signaling
Regarding the timings of Application of Retinoic acid, Applicant’s own specification evidences timings of activators of retinoic acid signaling are unpredictable. Specifically, the specification states “The duration of RA exposure is a key determinant for a switch-like conversion of hPSCs into neural stem cells expressing a mesencephalic identity” (pg. 59).
The instant specification evidences timings of the specific small molecules activators of retinoic acid signaling of all-trans RA, 9-cis RA, 13-cis RA and the xenobiotic RA-analogue tazarotenic acid (TA) analogues as a 48-hour pulse initiated between 0-2 DDC is required (Example 1).
The instant specification evidences timings of the specific small molecules activators of retinoic acid signaling of EC32 requires treatment for only 24 hours (Example 1).
Therefore, because the effects of timings of RA signaling are not predicable, Applicant is not enabled for all timings and durations of RA signaling for all possible activators.
Specific Concentrations of Activators of RA signaling
The instant specification evidences the required concentration range of the retinoic signaling activator all Trans RA of 200-400 nM is required for the majority of the population to be ventral midbrain dopaminergic progenitor cells.
The instant specification evidences the required concentration range of the retinoic signaling activators 9-cis RA, 13-cis RA and the xenobiotic RA-analogue tazarotenic acid (TA) analogues of 500 nM is required for the majority of the population to be ventral midbrain dopaminergic progenitor cell (Example 1).
The instant specification evidences the required concentration range of the retinoic signaling activator EC23 required a 20-fold reduction in concentration and treatment of cells only for 24 hours (Figure 9c (Supplementary Fig. 3c)) for the majority of the population to be ventral midbrain dopaminergic progenitor cells (Example 1).
Therefore, because the effects of different Specific concentrations of Activators of RA signaling are not predicable, Applicant is not enabled for concentrations of all activators of RA signaling.
State of the Prior Art and Unpredictability of the Art
Concerning the state of the art, Applicant is directed to the art of record of Ashton et al. (US-2019/0024046-A1; henceforth “Ashton”). Ashton discloses a method for differentiating stem cells (human pluripotent stem cells) into neural rosettes (“singular rosette structure having regional neural progenitor phenotypes” abstract), the method comprising contacting a plurality of stem cells with an effective amount of at least one activator of retinoic acid (RA) signaling (“in some embodiments, a retinoic acid receptor agonist is also included to facilitate neural differentiation into certain neuronal lineages depending on the concentration of retinoid used” para. [0079]), and culturing the stem cells under conditions sufficient to cause differentiation of the stem cells into a cell population comprising ventral midbrain dopaminergic progenitor cells (“singular rosette structure having regional neural progenitor phenotypes”; abstract); wherein the culturing comprises dual SMAD inhibition (TGFβ signaling antagonist and a BMP signaling antagonist; para. [0080]) wherein the first SMAD inhibitor is one or more inhibitor of TGFB/Activin Nodal signalling (TGFβ signaling antagonist para. [0080]) and the second SMAD inhibitor is one or more inhibitor of BMP signalling (BMP signaling antagonist para. [0080]), and contacting the stem cells with at least one activator of Hedgehog (Hh) signalling (“exposing the seeded cells to RA and Sonic Hedgehog (SHH) or a SHH signaling agonist for about 1 to about 5 days” para. [0006, 0054])
wherein the stem cells are contacted with the activator of retinoic acid (RA) signalling for 1-4 days(“exposing the seeded cells to RA and Sonic Hedgehog (SHH) or a SHH signaling agonist for about 1 to about 5 days” para. [0006, 0054]));
wherein the stem cells are pluripotent cells (human pluripotent stem cells).
Ashton discloses the activator of Hh signalling is Sonic Hedgehog or Purmorphamine (para. [0006, 0016, 0054, 0056, 0123, 0143]; Claim 13), which both increase smoothened signaling.
Ashton discloses the activator of retinoic acid (RA) signalling is all-trans retinoic acid (ATRA) (para. [0079]), which increases activation of a retinoic acid receptor.
However, Ashton is silent to expression of forkhead box protein A2 (FOXA2) and LIM homeobox transcription factor 1 alpha (LMX1A) in the obtained cells, and Ashton further discloses the obtained cells are spinal motor neuron progenitors (para. [0008, 0016, 0018-0019, 0036, 0054, 0056, 0098, 0105, 0107, 0122-014, 0126-0127, 0134-0135, 0142-0143]; claim 25) and therefore the method of Asthon, which anticipates the active method steps of instant claims, arrives at a structurally and functionally distinct cell type and indicates that the method as claimed cannot predictably arrive at the claimed cells which are ventral midbrain dopaminergic progenitor cells that express FOXA2 and LMX1A.
Applicant is also directed to Applicant’s own argument that “all of the data and support in Ashton teaches a different cell population is produced, specifically, Nkx6. 1 +/Olig2+ spinal motor neuron progenitors” (pg. 11).
Unpredictability of the Art and the Quantity of Experimentation Necessary
As the state of the art, the evidence in the instant specification, and Applicant’s arguments demonstrate, the obstacles that hinder the use of the claimed method are not easy tasks to be done or solely routine experimentation to enabled particular embodiments of the claimed method to obtain the specific cell type of ventral midbrain dopaminergic progenitor cells that express FOXA2 and LMX1A required by instant claims (claim 1 and dependents), or to arrive to arrive at the claimed and required functional result of the cell population comprises at least 50%, at least 60%, at least 70%, or at least 80% ventral midbrain dopaminergic progenitor cells at least after 7 days after first contacting said plurality of stem cells with the at least one activator of Retinoic Acid (RA) signalling (instant claim 5). The type of experimentation would require new methodologies. This level of experimentation goes beyond what would be routine optimization know at the time of filing. As such, the amount of experimentation would be undue.
The physiological art is recognized as unpredictable (MPEP 2164.03). As set forth in In re Fisher, 166 USPQ 18 (CCPA 1970), compliance with 35 USC 112(a) requires: “That scope of claims must bear a reasonable correlation to scope of enablement provided by specification to persons of ordinary skill in the art; in cases involving predictable factors, such as mechanical or electrical elements, a single embodiment provides broad enablement in the sense that, once imagined, other embodiments can be made without difficulty and their performance characteristics predicted by resort to known scientific laws; in cases involving unpredictable factors, such as most chemical reactions and physiological activity, scope of enablement varies inversely with degree of unpredictability of factors involved.” Moreover, the courts have also stated that reasonable correlation must exist between scope of exclusive right to patent application and scope of enablement set forth in the patent application (27 USPQ2d 1662 Ex parte Maize!.). In view of the foregoing, due to the lack of sufficient guidance provided by the specification regarding the issues set forth above, the state of the relevant art, and the breadth of the claims, it would have required undue experimentation for one skilled in the art to practice the instant broadly claimed invention.
Scope of Enablement - Conclusion
In conclusion, the breadth of the claims lack enablement because the specification provides limited working examples with specific concentrations of specific types of small molecule activators of retinoic acid signaling and specific timings and durations of the activators to arrive at the claimed required result of a cell population comprising of ventral midbrain dopaminergic progenitor cells that express FOXA2 and LMX1A. The state of the art at the time of effective filing fail to provide specific guidance that supplement to shortcomings of the specification and the instant specification further evidences that the breadth of claims cannot predictably be performed. Further, a great deal of new methodology would need to be developed to enable the full breadth of the claims and this level of experimentation is undue.
Withdrawn Claim Rejections - 35 USC § 112(b)
The rejection of claim 56 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite as set forth in the previous office action is withdrawn in view of Applicant’s amendments.
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 19 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 19 recites the at least one activator of Retinoic Acid (RA) signalling can be “a retinoic acid analogue” which is broader than the “activator of Retinoic Acid (RA) signalling” as recited in claim 1, upon which claim 19 depends, because claim 1 requires “the at least one activator of retinoic acid (RA) signalling increases activation of a retinoic acid receptor” which is more specific than the “retinoic acid analogue” because not all retinoic acid analogues have the function of increasing activation of a retinoic acid receptor. Therefore, because the “retinoic acid analogue” is broader than the previously recited “activator of Retinoic Acid (RA) signalling” it is unclear how this embodiment further limits the claim 19, on which it depends, and it is also unclear what the scope of the “retinoic acid analogue” is intended to encompass.
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.
Claim 19 remains 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 19 recites the at least one activator of Retinoic Acid (RA) signalling can be “a retinoic acid analogue” which is broader than the “activator of Retinoic Acid (RA) signalling” as recited in claim 1, upon which claim 19 depends, because claim 1 requires “the at least one activator of retinoic acid (RA) signalling increases activation of a retinoic acid receptor” which is more specific than the “retinoic acid analogue” because not all retinoic acid analogues, have the function of increasing activation of a retinoic acid receptor required by claim 1, upon which claim 19 depends. Because claim 19 recites embodiments that are broader than the claim upon which it depends, it cannot further limit those embodiments.
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.
Withdrawn Claim Rejections - 35 USC § 112
Improper Markush
The rejection of claim 19 on the basis that it contains an improper Markush grouping of alternatives as set forth in the previous office action is withdrawn in view of Applicant’s amendments.
Withdrawn Claim Rejections - 35 USC § 102
The rejection of claims 1-2, 5, 14, 17, 19, 21-22 and 56-58 under 35 U.S.C. 102(a)(1) as being anticipated by Ashton et al. (US-2019/0024046-A1; henceforth “Ashton”) as set forth in the previous office action is withdrawn in view of Applicant’s amendments and arguments of record.
Moot Claim Rejections – 35 USC § 102
The rejection of claims 3-4 under 35 U.S.C. 102(a)(1) as being anticipated by Ashton et al. (US-2019/0024046-A1; henceforth “Ashton”) as set for the in the previous office action is moot in view of the cancellation of these claims.
Withdrawn Claim Rejections - 35 USC § 103
The rejection of claim 15 under 35 U.S.C. 103 as being unpatentable over Ashton et al. (US-2019/0024046-A1; henceforth “Ashton”) in view of Chambers et al. (Nat Biotechnol . 2009 Mar;27(3):275-80. Epub 2009 Mar 1.; see IDS filed 21st, August, 2023; henceforth “Chambers”) as set forth in the previous office action is withdrawn in view of Applicant’s amendments and arguments of record.
The rejection of claims 25 and 55 under 35 U.S.C. 103 as being unpatentable over Ashton et al. (US-2019/0024046-A1; henceforth “Ashton”) in view of Cooper et al. (WO-2011/130675-A2; see IDS filed 24th, April, 2023; henceforth “Cooper”) as set forth in the previous office action is withdrawn in view of Applicant’s amendments and arguments of record.
Conclusion
No claim is allowable.
Correspondence
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/BRIANA N EBBINGHAUS/Examiner, Art Unit 1632
/EMILY A CORDAS/Primary Examiner, Art Unit 1632
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