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
Claims 1-10 and 12-31 are pending.
Claims 1-9 and 13-19 are withdrawn.
Claims 10, 12 and 20-31 are under examination.
New Claim Objections
Claims 22-31 are objected to because of the following informalities:
Claims 22-23 and 27-28 use the abbreviation “MAP” which has not been spelled out upon first use.
Claims 22, 24, 27 and 29 use the abbreviation “TUJ” which has not been spelled out upon first use.
Claims 25-26 and 30-31 use the abbreviation “NGN” which has not been spelled out upon first use.
Although claims are allowed abbreviations, if an abbreviation is not spelled out upon first use in a claim, MPEP §2429 states that Applicant only use abbreviations that are specifically defined in "WIPO Standard ST.25 (2009)” or that are well known and would be clear to someone who had not read the invention description.
Appropriate correction is required.
Moot Claim Rejections - 35 USC § 101
The rejection of claim 11 under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea (mental process) without significantly more as set forth in the previous office action is moot in view of the cancellation of this claim.
Withdrawn Claim Rejections - 35 USC § 101
The rejection of claims 10, 12 and 20 under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea (mental process) without significantly more as set forth in the previous office action is withdrawn in view of Applicant’s amendments and arguments of record.
New Claim Rejections - 35 USC § 112 (a)
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 22-23 and 27-28 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.
In the amendment filed 17th, February, 2026, claims 22-23 and 27-28 were amended to include the limitation that the marker is “MAP” and claims 23 and 28 were amended to include the limitation that the marker is “MAP1.” These new limitations appear 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 a specific recitation of the limitation.
The closest support for the limitations is the disclosure of MAP2 as a marker (para. [0042, 0099, 0112, 0114]). The disclosure of one specific MAP protein (MAP2) as a marker does not support the full breadth of the genus of MAP proteins as markers. Additionally, the disclosure of one specific MAP protein (MAP2) as a marker also does not support the limitation of another, structurally distinct species of MAP protein (the newly claimed limitation of MAP1).
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 full genus of MAP or the specific species of MAP1 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 17th, February, 2026, have been fully considered but are not found persuasive.
Applicant argues “Applicant respectfully submits that the disclosure as filed fully supports the above amendments, for example, as described below. Therefore, Applicant respectfully submits that the above amendments introduce no new matter” (pg. 7).
In response, Applicant has not provided the location of support for this amendment and for the reasons set forth above the limitations appear to be new matter.
When filing an amendment an applicant should show support in the original disclosure for new or amended claims. See MPEP §§ 714.02 and 2163.06 ("Applicant should ... specifically point out the support for any amendments made to the disclosure.") The claim is a new or amended claim, the support for the limitation is not apparent, and applicant has not pointed out where the limitation is supported (see MPEP 2163 (I)).
Moot Claim Rejections - 35 USC § 112(b)
The rejection of claim 11 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 moot in view of the cancelation of the claim.
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.
Claims 10 and 20-29 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 10 recites “screened based on a positive rate of a marker for the neural cell,” which includes the relative language “positive rate.” A claim may be rendered indefinite when a limitation of the claim is defined by reference to an object and the relationship between the limitation and the object is not sufficiently defined. That is, where the elements of a claim have two or more plausible constructions such that the examiner cannot readily ascertain positional relationship of the elements, the claim may be rendered indefinite. See, e.g., Ex parte Miyazaki, 89 USPQ2d 1207 (Bd. Pat. App. & Inter. 2008) (precedential) and Ex parte Brummer, 12 USPQ2d 1653 (Bd. Pat. App. & Inter. 1989). In the instant case the “positive rate” of the marker is dependent on some reference or control value, which is not sufficiently defined (see MPEP 2173.05(b)).
By nature of their ultimate dependency on claim 10, claims 20-26 are also rejected because they do not clarify the issue.
Claim 27 recites “wherein a marker is MAP or TUJ.” However claim 12, upon which claim 27 depends, does not recite a marker and claim 12 does not recite a method step that clearly includes or requires a marker. Therefore, the scope of claim 27 is indefinite because it is unclear how the marker recited in claim 27 is part of the method.
By nature of their dependency on claim 27, claims 28 and 29 are also rejected because they do not clarify the issue.
Moot Claim Rejections - 35 USC § 102
The rejection of claim 11 under 35 U.S.C. 102(a)(1) as being anticipated by Wernig et al. (US-20170369840-A1; see IDS filed 27th, December, 2022; henceforth “Wernig”) as set forth in the previous office action is moot in view of the cancellation of this claim.
Withdrawn Claim Rejections - 35 USC § 102
The rejection of claims 10 and 12 under 35 U.S.C. 102(a)(1) as being anticipated by Wernig et al. (US-20170369840-A1; see IDS filed 27th, December, 2022; henceforth “Wernig”) as set forth in the previous office action are withdrawn in view of Applicant’s amendments.
Withdraw Claim Rejections - 35 USC § 103
The rejection of claim 20 under 35 U.S.C. 103 as being unpatentable over Wernig et al. (US-20170369840-A1; see IDS filed 27th, December, 2022; henceforth “Wernig”) in view of Sachdeva et al. (Proc Natl Acad Sci U S A. 2010 Jun 22;107(25):11602-7. Epub 2010 Jun 7.; henceforth “Sachdeva”) as set forth in the previous office action are withdrawn in view of Applicant’s amendments.
New 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.
Claims 10, 12, 22, 24-27, and 29-31 are rejected under 35 U.S.C. 103 as being unpatentable over Wernig et al. (US-20170369840-A1; see IDS filed 27th, December, 2022; henceforth “Wernig”) in view of Song et al. (KR-20200140413-A; citations refer to attached translation; henceforth “Song”).
Regarding claims 10 and 12, Wernig discloses a method for screening candidate agents for activity in converting cells into neuronal cells (“methods are for screening candidate agents for activity modulating the direct conversion of somatic cells into induced neuronal cells (iNs)” para. [0010]); see also abstract; para. [0006-0007, 0014, 0019-0020, 0037, 0108, 0111, 0179-0184, 0196, 0201, 0215, 0247-0248, 0253]; Figures 1, 6-7; Example 2) comprising:
introducing a differentiation factor (“three or more factors selected from an Asel agent, a Ngn agent, a Brn agent, a NeuroD agent, a Mytl agent, an Olig agent or a Zic agent” para. [0007]; see also “one or more neuron reprogramming (NR) factors” para. [0008] and para. [0009-0011, 0014, 0018-0020, 0025, 0028-0029, 0045, 0047-0052, 0056-0062, 0065-0066, 0070, 0073-0075, 0082-0085, 0087, 0098-0099, 0114, 0116, 0126, 0136-0139, 0144-0151, 0158, 0160-0174, 0180, 0187, 0190, 0196, 0198-0199, 0208-0211, 0213, 0215-0216, 0218, 0222, 0225, 0229, 0242-0249, 0251]; Figures 5-7, 12, 15-16; Table 1; claims 1 and 4) into a pluripotent stem cell (“ “non-neuronal cells may be somatic cells or may be pluripotent cells” para. [0049]:see also para. [0007, 0012, 0037, 0043, 0049, 0056-0057, 0087, 00141, 0144, 0153, 0155, 0177, 0242, 0251]; claims 1-6, 10-13) (see also “NR factors are provided to somatic or pluripotent cells in the context of a NR system” para. [0057]) and differentiating the cell into a neural cell (neurons; abstract);
applying a candidate drug (“candidate agent”; abstract; para. [0006, 0010, 0037, 0106, 0108-0111, 0179-0184]) to a cell during differentiation of the pluripotent stem cell into the neural cell or to the differentiated neural cell ; and
screening the candidate drug on the basis of the neural cell (“the effect of the candidate agent assessed by monitoring output parameters such as iN survival” para. [0106]; see also para. [0049-0051, 0068, 0076, 0079-0080, 0085, 0139-0140, 0151-0152, 0174-0175, 0182, 0226]; Figure 1).
Regarding claim 10, further to the discussion of claim 1 above, Wernig discloses the candidate drug is screened based on the differentiation efficiency of the cells (“efficiency of reprogramming may be determined” para. [0088];see also para. [0008, 0016, 0024, 0029, 0053, 0192, 0202-0203, 0208, 0226, 0248]; Figures 3, 11, 16; claims 1 and 3) and Wernig discloses the candidate drug is screened based on a positive rate of a marker for the neural cell (“for such a screen…where an observed increase in the level of RNA or protein of a neuronal gene, e.g. a 1.5-fold, a 2-fold, a 3-fold or more increase in the amount of RNA or protein from a neuronal-specific gene, e.g., Tau, Beta-III Tubulin ( encoding the protein Tuj 1), MAP2, and the like, over that observed in the culture absent the candidate agent would be an indication that the candidate agent was an agent that promotes reprogramming to a neuronal fate…”; para. [0080]).
Regarding claim 12, Wernig discloses the candidate drug (“candidate agent”) is screened based on the survival rate of the neural cell (“the effect of the candidate agent assessed by monitoring output parameters such as iN survival” para. [0106]; see also para. [0049-0051, 0068, 0076, 0079-0080, 0085, 0139-0140, 0151-0152, 0174-0175, 0182, 0226])).
Regarding claim 12, further to the discussion of claim 10 above, Wernig discloses the candidate drug (“candidate agent”) is screened based on the survival rate of the neural cell (“the effect of the candidate agent assessed by monitoring output parameters such as iN survival” para. [0106]; see also para. [0049-0051, 0068, 0076, 0079-0080, 0085, 0139-0140, 0151-0152, 0174-0175, 0182, 0226])).
However, regarding claims 10, 12 and 21 , although Wernig teaches the method in pluripotent stem cells, and Wernig teaches the methods are for screening candidate agents for activity in converting cells into neuronal cells (abstract), Wernig does not disclose the method using a pluripotent stem cell derived from a neurological disease patient wherein the neurological disease patient is an Alzheimer's disease patient.
Nevertheless, regarding claims 10, 12, and 21, Song teaches a method comprising: introducing a differentiation factor into a pluripotent stem cell derived from a Alzheimer's disease patient and differentiating the cell into a neural cell (“Differentiation of induced pluripotent stem cells into cortical neurons” pg. 4; see also claims; Examples 1-3 pg. 4; see in particular Example 1 pg. 4 ).
Therefore, regarding claims 10 and 12, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to practice the method of Wernig, and simply substitute the known prior art element of the pluripotent stem cell derived from a Alzheimer's disease patient of Song for the pluripotent stem cell of Wernig (instant claims 10 and 12) and the method step of introducing a differentiation factor into a pluripotent stem cell derived from a Alzheimer's disease patient and differentiating the cell into a neural cell (instant claim 21) to obtain the predictable result of a method for screening candidate agents for activity in converting cells into neuronal cells. One of ordinary skill would have been motivated to do so as taught by Wernig to screen candidate agents for activity in converting the patient-derived iPSCs of Song into neuronal cells (abstract). Regarding the reasonable expectation of success, Wernig evidences methods for screening candidate agents for activity in converting cells into neuronal cells comprising introducing a differentiation factor into a pluripotent stem cell and differentiating the cell into a neural cell, applying a candidate drug to a cell during differentiation of the pluripotent stem cell into the neural cell or to the differentiated neural cell; and screening the candidate drug on the basis of the neural cell.
Regarding the preamble of claims 10 and 12, the preamble merely states the purpose or intended use of the invention (“screening a neurological disease therapeutic drug”), rather than any distinct definition of any of the claimed invention’s limitations and therefore the preamble is not considered a limitation and is of no significance to claim construction (see MPEP 2111.02) See also Rowe v. Dror, 112 F.3d 473, 478, 42 USPQ2d 1550, 1553 (Fed. Cir. 1997) ("where a patentee defines a structurally complete invention in the claim body and uses the preamble only to state a purpose or intended use for the invention, the preamble is not a claim limitation"). In the instant case, Wernig in view of Song suggest the active method steps above and therefore the suggested method is capable of meeting the intended use of screening a neurological disease therapeutic drug.
Regarding claims 22, 24, 27 and 29, further to the discussion of claims 10 or 12 above, Wernig teaches the marker is MAP2 which is a MAP (MAP2; Figures 1J, 2B, 4E-F, 5F, 6C, 8A, 10A-B, 13A-B, 14C, 15C, 16F-G; para. [0014-0015, 0018, 0021, 0023, 0026-0029, 0038, 0086, 0088, 0180-0181, 0191 , 0194, 0198, 0200-0201, 0205, 0209, 0219, 0234, 0244, 0246, 0248, 0253, 0247]; Example 1) (instant claims 22 and 27) or TUJ1 which is a TUJ (TUJ1; Figures 1, 2A, 3A, 3I, 5A, 6A, 7A, 8C, 11A, 12, 13G, 14A, 15B; para. [0014-0016, 0018-0021, 0024-0029, 0038, 0086, 0088, 0180, 0191-0192, 0197-0198, 0201-0203, 0207, 0209, 0217-0219, 0222-0223, 0232, 0234, 0244, 0247-0248, 0253, 0257]; Example 1) (instant claims 22, 24, 27 and 29)
Regarding claims 25-26 and 30-31, further to the discussion of claims 10 or 12 above, Wernig teaches the differentiation factor is NGN2 (para. [0059]) (instant claims 26 and 31) which is an NGN (“Ngn agent” para. [0007] see also para. [0008-0009, 0057, 0059, 0073])(instant claims 25 and 30).
Hence, the claimed invention as a whole was prima facie obvious.
Claim 20 is rejected under 35 U.S.C. 103 as being unpatentable over Wernig et al. (US-20170369840-A1; see IDS filed 27th, December, 2022; henceforth “Wernig”) in view of Song et al. (KR-20200140413-A; citations refer to attached translation; henceforth “Song”) as applied to claim 1 above, and in further view of Sachdeva et al. (Proc Natl Acad Sci U S A. 2010 Jun 22;107(25):11602-7. Epub 2010 Jun 7.; henceforth “Sachdeva”). The teachings of Wernig and Song above are incorporated herein in their entirety.
Regarding claim 20, further to the discussion of claim 10 above, although Wernig teaches the neurons produced can be used for transplantation (abstract; para. [0006, 0011, 0037, 0089, 0102-0104, 0142, 0178]) Wernig does not disclose a step of removing an undifferentiated cell, and Song is silent to this step.
Nevertheless, regarding claim 20, Sachdeva teaches a method comprising differentiating neural cells from pluripotent stem cells for use in transplant comprising a step of removing the undifferentiated cells to reduce the formation of tumors and lead to neuron-rich transplants displaying mature neuronal morphologies (pg. 11606 col. 1 3rd para.).
Therefore, regarding claim 20, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to practice the method as suggested by Wernig in view of Song, and combine the known prior art element of the step of removing undifferentiated cells of Sachdeva to obtain the predictable result of cells for use in transplant. One of ordinary skill would have been motivated to do so as taught by Sachdeva to reduce the formation of tumors and lead to neuron-rich transplants displaying mature neuronal morphologies (pg. 11606 col. 1 3rd para.). Regarding the reasonable expectation of success, Sachdeva evidences removing undifferentiated cells (pg. 11606 col. 1 3rd para.).
Hence the claimed invention as a whole was prima facie obvious.
Claims 23 and 28 are rejected under 35 U.S.C. 103 as being unpatentable over Wernig et al. (US-20170369840-A1; see IDS filed 27th, December, 2022; henceforth “Wernig”) in view of Song et al. (KR-20200140413-A; citations refer to attached translation; henceforth “Song”) as applied to claim 1 above, and in further view of Son et al. (J Neurosci. 1999 Jan 1;19(1):10-20.; henceforth “Son”)
The teachings of Wernig and Song above are incorporated herein in their entirety.
Regarding claims 23 and 28, further to the discussions of claims 10, 12, 22, and 27 above, although Wernig teaches the marker is from a neuron-specific gene (para. [0080]) and Wernig teaches MAP2 as a marker (MAP2; Figures 1J, 2B, 4E-F, 5F, 6C, 8A, 10A-B, 13A-B, 14C, 15C, 16F-G; para. [0014-0015, 0018, 0021, 0023, 0026-0029, 0038, 0086, 0088, 0180-0181, 0191 , 0194, 0198, 0200-0201, 0205, 0209, 0219, 0234, 0244, 0246, 0248, 0253, 0247]; Example 1), Wernig and Song are silent to using MAP1 as a marker.
Nevertheless, regarding claims 23 and 28, Son teaches MAP1 and MAP2 as general neuronal markers (“general neuronal markers, such as NSE, MAP1, MAP2, NF-M, and synaptophysin” Table 1; pg. 14).
Therefore, regarding claims 23 and 28, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to practice the method as suggested by Wernig in view of Song, and simply substitute the known prior art element of the MAP1 marker of Son for the MAP2 marker of Wernig to obtain the predictable result of a marker for neurons. One of ordinary skill would have been motivated to do so because MAP1 is a well known marker for neurons, as taught by Son. Regarding the reasonable expectation of success, Son evidences a step of measuring MAP1 expression as a marker for neurons (Table 1; pg. 14 col. 2 2nd para.; pg. 12 col. 1 2nd para.).
Hence, the claimed invention as a whole was prima facie obvious.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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
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