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 .
DETAILED ACTION
RESPONSE TO AMENDMENT
Status of Application/Amendments/claims
2. Applicant’s amendment filed August 25, 2025 is acknowledged. Claims 2, 12-14, 17 and 20-28 are canceled. Claims 1, 3-5, 7, 11, 18-19 are amended. Claims 29-33 are newly added. Claims 1, 3-11, 15-16, 18-19 and new claims 29-33 are pending in this application. Election was made without traverse in the reply filed on February 16, 2024.
3. Claims 1, 3-11, 15-16, 18-19 and 29-33 are under examination in this office action.
4. Applicant’s arguments filed on August 25, 2025 have been fully considered but they are not deemed to be persuasive for the reasons set forth below.
Claim Rejections/Objections Withdrawn
5. The rejection of claims 1, 3-11, 15-16 and 18-19 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, lack of scope of enablement is withdrawn in response to Applicant’s amendment to the claims and arguments on p. 6-8 of the response.
The rejection of claims 1, 3-11, 15-16 and 18-19 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112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement is withdrawn in response to Applicant’s amendment to the claims and arguments on p. 6-8 of the response.
Claim Rejections/Objections Maintained
In view of the amendment filed on August 25, 2025, the following rejections are maintained.
Claim Rejections - 35 USC § 103
6. 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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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, 3-9, 11, 15-16, 18-19 and 29-33 are rejected under 35 U.S.C. 103 as being unpatentable over Mendlein et al. (US2012/0207744) in view of Mutsuga et al. (Mol. Endocrinol. 2001; 15:2149-2156), Bancel et al. (WO2013151670), Valerius et al. (Dev. Dyn. 1995; 203:337-351), Shoemaker et al. (US2013/0189780), and Blaschuk et al. (WO200059939). The rejection is maintained for the reasons of record and the reasons set forth below.
Claims 7-8 and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Mendlein et al. (US2012/0107744) in view of Mutsuga et al. (2001), Bancel et al. (WO2013151670), Valerius et al. (1995), Shoemaker et al. (US2013/0189780), and Blaschuk et al. (WO200059939) as applied to claims 1, 3-9, 11, 15-16, 18-19 and 29-33 above, and further in view of Chan et al. (Nat. Neurosci. 2017; 20:1172-1179), Chen et al. (J. Neurosci. Meth. 2012; 207:172-180), Wulansari et al. (Stem cell Rep. 2017. dx.doi.org/10.1016/j.stemcr.2017.08.017) and Bujalka et al. (PloS Biol. 2013; 11:e1001625.doi.10.1371/journal.pbio.1001625). The rejection is maintained for the reasons of record and the reasons set forth below.
Claims 1, 3-9, 11, 15-16, 18-19 and 29-33 as amended are drawn to a method for promoting locomotor functional recovery after a spinal cord injury in a mammalian subject by administering to the subject a therapeutically effective amount of Gsx1 protein or Gsx1-CPP fusion protein or a nucleic acid molecule encoding the Gsx1 or Gsx1-CPP fusion protein thereof, wherein the Gsx1 protein or Gsx1 portion of the Gsx1-CPP fusion protein comprises at least 98% or 99% or 100% sequence identity to SEQ ID NO:2 or 4, and wherein the CPP comprises at least 98% or 99% or 100% sequence identity to any one of SEQ ID NOs:61-79.
Response to Arguments
On p. 8-15 of the response, Applicant argues that: i) Shoemaker, Valerius, Bancel, Mutsuga and Blaschuk in combination do not teach or suggest Gsx1 or Gsx1-CPP as an activator and wherein the Gsx1 comprises at least 98% sequence identity to SEQ ID NO:2 or 4 because: 1) Shoemaker does not teach or suggest a full-length Gsx1 as an activator; 2) none of Valerius, Bancel, Mutsuga and Blaschuk teach or suggest using Gsx1 or Gsx1-CPP as an activator. ii) Mendlein as evidenced by Kozlova or Tesar does not disclose or suggest Gsx1 is involved in promoting locomotor functional recover after a spinal cord injury because: 1) Mendlein is silent about involvement of Gsx1 in promoting locomotor functional recovery after a spinal cord injury; 2) Tesar and Kozlova cannot cure the deficiency of Mendlein because Tesar teaches promoting myelination of the CNS in a subject comprising administering reprogrammed glial cells generated by infecting somatic cells with a lentiviral vector to deliver reprogramming factor including Gsx1; 3) Kozlova taches neural stem cells expressing different transcription factors (TFs) but these TFs do not include Gsx1 ([0047]-[0048]). iii) There is no reasonable expectation of success to modify the cited references to arrive at the claimed method because: 1) Mendlein provides no data and all examples are prophetic; 2) neither Kozlova nor Tesar provides data for Gsx1; 3) it is highly unpredictable whether an agent will be effective in promoting locomotor functional recovery after spinal cord injury as shown in Dr. Li’s declaration filed March 19, 2025, Figure 8B of Exhibit B and Figure 6H of Exhibit A.
Applicant's arguments have been fully considered but they are not found persuasive. Contrary to Applicant's arguments, the examiner asserts that based on MPEP §2141, MPEP2141-I, rationales identified by the Court in KSR (KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 398, 82 USPQ2d 1385 (2007)), MPEP2141-II, the basic factual inquires of Graham v. John Deere Co.(Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966)),and MPEP §2141.01-2147.03, the cited references do render the claimed invention obvious because:
i. Applicant cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007).
In this case, Mendlein teaches a method of in vivo cell therapy in CNS disorders including cerebral stroke, brain trauma, ischemic injury and spinal cord injury in a subject, comprising administering to the subject a composition comprising one or more activators to modulate components associated with the potency of cells, wherein the one or more activators include polypeptides or DNA molecules of pluripotency factors, transcription factors or artificial transcription factors, and wherein the components include Gsh1 (which is also called Gsx1 as instantly claimed) (paragraphs [1344]-[1347]; [1368]; [1373]). Mendlein teaches that the DNA molecules comprise a plasmid or viral vector including lentiviral or adeno-associated vector as in claims 5-6, or operably linked to a promoter, wherein the promoter is linked to a neural-specific enhancer including a constitutive promoter as in claims 7-8 (see paragraphs [0708]; [0770]-[0771]; [1030]; [1044]-[1045];[1221]-[1236]), administering directly into the CNS or intracerebroventricular injection as in claims 15-16 (see paragraph [1210]), wherein the DNA molecule is in a pharmaceutical composition as in claim 18 (see paragraph [1184]), and administering comprising at least two separate administrations as in claim 19 (see paragraph [1209]).
While Mendlein does not explicitly teach Gsx1 or Gsx1-CPP fusion protein as activators, wherein the Gsh1/Gsx1 protein comprises at least 98%-100% sequence identity to SEQ ID NO:2 or 4 as in claims 1, 3 or 29, or the nucleic acid molecule encoding the Gsx1 or the Gsx1 portion of the Gsx1-CPP fusion protein comprises SEQ ID NO:1 or 3 as in claim 4, Mutsuga, Bancel and Valerius teach these limitations and provide motivation and an expectation of success in using the claimed Gsx1 or the claimed nucleic acid molecule encoding the Gsx1 thereof in the method of Mendlein for treating CNS disorders including spinal cord injury because Mutsuga, Bancel and Valerius teach the protein sequence of Gsx1/Gsh1 comprising at least 98%, 99% or 100% identical to instant SEQ ID NOs: 2 or 4, or the DNA sequence of Gsx1/Gsh1 comprising instant SEQ ID NO:1 or 3.
Mutsuga teach that human Gsh1 has a nucleic acid sequence that is 99.9% identical to instant SEQ ID NO:1 (see the sequence alignment below; p. 2150, figure1). Bancel et al. (WO2013151670) teach that human Gsh1 has an amino acid sequence that is 100% identical to instant SEQ ID NO:2 or has a nucleic acid sequence that is 100% identical to instant SEQ ID NO:1 (see the sequence alignment below).
Valerius et al. teaches that human Gsh1 has an amino acid that is 100% identical to instant SEQ ID NO:4 or has a nucleic acid sequence that is 99.2% identical to instant SEQ ID NO:3 (see the sequence alignment below; p. 339-340, figures 2-3).
A person of ordinary skill in the art would have recognized that selecting and applying the known Gsh1/Gsx1 protein sequence comprising at least 98%-100% sequence identity to instant SEQ ID NO:2 or 4 or the known Gsh1/Gsx1 DNA sequence comprising instant SEQ ID NO: 1 or 3 and the known technique disclosed by Mutsuga, Bancel and Valerius to the Mendlein’s method would have yielded the predictable result of increasing modulation of Gsh1/Gsx1 in increasing the potency of a cell and thereby treating CNS disorders including cerebral stroke, brain trauma, ischemic injury and spinal cord injury in a subject, and resulted in an improved method for treating CNS disorders including cerebral stroke, brain trauma, ischemic injury and spinal cord injury in a subject.
Using the known Gsh1/Gsx1 protein sequence comprising at least 98%-100% sequence identity to instant SEQ ID NO:2 or 4 or the known Gsh1/Gsx1 DNA sequence comprising instant SEQ ID NO: 1 or 3 in the Mendlein’s method would generate the claimed Gsh1/Gsx1 protein or DNA encoding the Gsh1/Gsx1 protein thereof, and expand application of the Mendlein’s method for treating CNS disorders including spinal cord injury, and would also increase patient’s satisfaction with treatment of CNS disorders including spinal cord injury in a subject using Gsh1/Gsx1 protein or DNA encoding the Gsh1/Gsx1 protein thereof.
Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to select and apply the known Gsh1/Gsx1 comprising at least 98%-100% sequence identity to instant SEQ ID NO:2 or 4 or the known nucleic acid molecule encoding the Gsx1 protein comprising instant SEQ ID NO: 1 or 3 and the known technique disclosed by Mutsuga, Bancel and Valerius to the Mendlein’s method to express Gsh1/Gsx1 to increase the potency of a cell modulated by Gsh1/Gsx1, and yield the predictable result of treating CNS disorders including cerebral stroke, brain trauma, ischemic injury and spinal cord injury in a subject.
While Mendlein, Mutsuga, Bancel and Valerius do not explicitly teach a CPP fusion protein of Gsh1/Gsx1 recited in claim 1, or wherein the CPP comprises at least 95%, 98%, 99% or 100% identity to recited SEQ ID NOs: including SEQ ID NO:61 as in claims 11 and 30-32, Shoemaker and Blaschuk teach these limitations and provide motivation and an expectation of success in using the claimed Gsx1-CPP fusion protein or nucleic acid molecule thereof in the method of Mendlein, Mutsuga, Bancel and Valerius for treating CNS disorders including spinal cord injury because Shoemaker teaches using an artificial pluripotency transcription factor (APTF), wherein the APTF comprises polypeptide domains encoding a nuclear localization sequence (NLS), a DNA binding domain (DBD), and a transcriptional activation domain (TAD); and wherein the APTF comprises Gsh1 and a CPP including HIV TAT as in claim 1 and Blaschuk teaches use of a CPP derived from HIV TAT peptide having the amino acid sequence of instant SEQ ID NO:61 for generation of a CPP-fusion protein.
Shoemaker teaches a method of increasing the potency of a cell, comprising contacting the cell with one or more polynucleotides, each comprising an artificial pluripotency transcription factor (APTF), wherein the APTF comprises polypeptide domains encoding a nuclear localization sequence (NLS), a DNA binding domain (DBD), and a transcriptional activation domain (TAD); and wherein the APTF comprises Gsh1 and a CPP including HIV TAT as in claim 1 (see paragraphs [0012]-[0015]; [0024]-[0025]; [0034]-[0035]; [0043]; [0063]; [0075]-[0094]; [0099]), wherein the polynucleotide comprises a plasmid or viral vector including lentiviral or adeno-associated viral vector as in claims 5-6 (see paragraphs [0255]; [0265]-[0273]) or is operably linked to a promoter, wherein the promoter is a constitutive promoter, CMV promoter as in claims 8-9 (see paragraphs [0169]; [0171]-[0175]), different CPP sequences including RKKRRQRRR, KKRRQRRR, and RKKRRQRR (derived from HIV TAT protein); RRRRRRRRR; KKKKKKKKK; RQIKIWFQNRRMKWKK (from Drosophila Antp protein); RQIKIWFQNRRMKSKK (from Drosophila Ftz protein); RQIKIWFQNKRAKIKK (from Drosophila Engrailed protein); RQIKIWFQNRRMKWKK (from human Hox-A5 protein); and RVIRVWFQNKRCKDKK (from human Isl-1 protein) (see paragraph [0089]).
Blaschuk et al. (WO200059939) teach a CPP derived from HIV TAT peptide having the amino acid sequence of instant SEQ ID NO:61 (see the sequence alignment; p. 16-17; p. 28, claim 4).
A person of ordinary skill in the art would have recognized that selecting and applying the known protein or DNA of artificial pluripotency transcription factor (APTF) comprising Gsh1/Gsx1 or Gsh1/Gsx1-CPP, wherein the Gsh1/Gsx1 comprises at least 98%-100% sequence identity to instant SEQ ID NO:2 or 4, the known nucleic acid molecule encoding the Gsx1 protein or the Gsx1 portion of Gsx1-CPP fusion comprising instant SEQ ID NO: 1 or 3, the known CPP comprising at least 95%-100% identity to recited SEQ ID NOs: including SEQ ID NO:61, the known CMV promoter and the known technique disclosed by Shoemaker and Blaschuk to the method of Mendlein, Mutsuga, Bancel and Valerius, and would have yielded the predictable result of increasing modulation of Gsh1/Gsx1 in increasing the potency of a cell and thereby treating CNS disorders including cerebral stroke, brain trauma, ischemic injury and spinal cord injury in a subject, and resulted in an improved method for treating CNS disorders including cerebral stroke, brain trauma, ischemic injury and spinal cord injury in a subject.
Using the known artificial pluripotency transcription factor (APTF) comprising Gsh1/Gsx1 or Gsh1/Gsx1-CPP, wherein the Gsh1/Gsx1 comprises at least 98%-100% sequence identity to instant SEQ ID NO:2 or 4 or wherein the nucleic acid molecule encoding the Gsh1/Gsx1 portion of Gsh1/Gsx1-CPP comprises instant SEQ ID NO: 1 or 3, and wherein the known CPP comprises at least 95%-100% identity to recited SEQ ID NOs: including instant SEQ ID NO:61 and the known CMV promoter in the method of Mendlein, Mutsuga, Bancel and Valerius would expand application of the method of Mendlein, Mutsuga, Bancel and Valerius, and would increase the potency of a cell modulated by Gsh1/Gsx1 for treating CNS disorders including spinal cord injury, and would also increase patient’s satisfaction with treatment of CNS disorders including spinal cord injury in a subject.
Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to select and apply the known protein or DNA of artificial pluripotency transcription factor (APTF) comprising Gsh1/Gsx1 or Gsh1/Gsx1-CPP, wherein the Gsh1/Gsx1 comprises at least 98%-100% sequence identity to instant SEQ ID NO:2 or 4, the known nucleic acid molecule encoding the Gsx1 protein or the Gsx1 portion of Gsx1-CPP fusion comprising instant SEQ ID NO: 1 or 3, the known CPP comprising at least 95%-100% identity to recited SEQ ID NOs: including SEQ ID NO:61, the known CMV promoter and the known technique disclosed by Shoemaker and Blaschuk to the method of Mendlein, Mutsuga, Bancel and Valerius to express Gsh1/Gsx1 to increase the potency of a cell modulated by Gsh1/Gsx1, and yield the predictable result of treating CNS disorders including cerebral stroke, brain trauma, ischemic injury and spinal cord injury in a subject.
Accordingly, the rejection of claims 1, 3-9, 11, 15-16, 18-19 and 29-33 under 35 U.S.C. 103 as being unpatentable over Mendlein in view of Mutsuga, Bancel, Valerius, Shoemaker, and Blaschuk is maintained.
ii. In response to applicant’s argument that Mendlein provides no data and all examples are prophetic, and neither Kozlova nor Tesar provides data, based on MPEP, an actual working example is not required for compliance with the enablement requirement of 35 U.S.C. 112, first paragraph.
“An example may be ‘working' or ‘prophetic.' A working example is based on work actually performed. A prophetic example describes an embodiment of the invention based on predicted results rather than work actually conducted or results actually achieved.”
and also In in re Borkowski, the court held that
“The specification need not contain an example if the invention is otherwise disclosed in such manner that one skilled in the art will be able to practice it without an undue amount of experimentation. In re Borkowski, 422 F.2d 904, 908, 164 USPQ 642, 645 (CCPA 1970). See MPEP § 2164.02.
iv. In response to applicant’s argument related to unpredictability, it is noted that that the effect of Gsh1/Gsx1 on treating CNS disorders including cerebral stroke, brain trauma, ischemic injury and spinal cord injury or on promoting neurogenesis and neuronal function is known and not unpredictable because:
1) Mendlein teaches a method of in vivo cell therapy in CNS disorders including cerebral stroke, brain trauma, ischemic injury and spinal cord injury in a subject, comprising administering to the subject a composition comprising one or more activators to modulate components associated with the potency of cells, wherein the one or more activators include polypeptides or DNA molecules of pluripotency factors, transcription factors or artificial transcription factors, and wherein the components include Gsh1/Gsx1 as instantly claimed;
Kozlova teaches treating brain and spinal cord injury by delivering neural stem cells that are transfected with a construct encoding a transcription factor including Gsh1 and an exogenous inducer to induce neurogenesis (para [0047]-[0050]; [0068]-[0070] claims 8-9); and Tesar et al. (US10119123) teaches a method of promoting myelination in the CNS of a subject in need thereof including spinal cord injury comprising administering to the subject a population of reprogrammed glial cells wherein the reprogrammed glial cells are generated from somatic cells transfected with a reprogramming factor including Gsx1 (see col.2, line 54).
The difference between the claimed method and the method of Mendlein is instant SEQ ID NO:2 or 4 for Gsh1/Gsx1 recited in instant claims, or a CPP fusion protein, or wherein the CPP comprises at least 95%, 98%, 99% or 100% identity to recited SEQ ID NOs: including SEQ ID NO:61.
While Mendlein does not teach that Gsh1/Gsx1 comprises the sequence of instant SEQ ID NO:2 or 4 or at least 98% identity thereof, Mutsuga, Bancel and Valerius teach the protein sequence of Gsx1/Gsh1 comprising at least 98%, 99% or 100% identical to instant SEQ ID NOs: 2 or 4, or the DNA sequence of Gsx1/Gsh1 comprising instant SEQ ID NO:1 or 3. While Mendlein, Mutsuga, Bancel and Valerius do not explicitly teach a CPP fusion protein of Gsh1/Gsx1, or wherein the CPP comprises at least 95%, 98%, 99% or 100% identity to recited SEQ ID NOs: including SEQ ID NO:61, Shoemaker and Blaschuk teach using an artificial pluripotency transcription factor (APTF), wherein the APTF comprises Gsh1 and a CPP including HIV TAT and Blaschuk teaches use of a CPP derived from HIV TAT peptide having the amino acid sequence of instant SEQ ID NO:61 for generation of a CPP-fusion protein. Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to select and apply the known Gsh1/Gsx1 comprising at least 98%-100% sequence identity to instant SEQ ID NO:2 or 4 or the known nucleic acid molecule encoding the Gsx1 protein comprising instant SEQ ID NO: 1 or 3 and the known technique disclosed by Mutsuga, Bancel and Valerius to the Mendlein’s method to express Gsh1/Gsx1 to increase the potency of a cell modulated by Gsh1/Gsx1, and yield the predictable result of treating CNS disorders including cerebral stroke, brain trauma, ischemic injury and spinal cord injury in a subject.
It would also have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to select and apply the known protein or DNA of artificial pluripotency transcription factor (APTF) comprising Gsh1/Gsx1 or Gsh1/Gsx1-CPP, wherein the Gsh1/Gsx1 comprises at least 98%-100% sequence identity to instant SEQ ID NO:2 or 4, the known nucleic acid molecule encoding the Gsx1 protein or the Gsx1 portion of Gsx1-CPP fusion comprising instant SEQ ID NO: 1 or 3, the known CPP comprising at least 95%-100% identity to recited SEQ ID NOs: including SEQ ID NO:61, the known CMV promoter and the known technique disclosed by Shoemaker and Blaschuk to the method of Mendlein, Mutsuga, Bancel and Valerius to express Gsh1/Gsx1 to increase the potency of a cell modulated by Gsh1/Gsx1, and yield the predictable result of treating CNS disorders including cerebral stroke, brain trauma, ischemic injury and spinal cord injury in a subject.
2) The Dr. Cai’s declaration under 37 CFR 1.132 filed 03/20/2025 is insufficient to overcome the rejection of claims 1, 3-9, 11, 15-16, 18-19 and 29-33 based upon Mendlein in view of Mutsuga, Bancel, Valerius, Shoemaker, and Blaschuk under 35 USC 103 as set forth in the last Office action because: i) The declaration only include(s) statements which amount to an affirmation that i) a skilled artisan would be able to identify sequences that are at least 95% identical to SEQ ID NO:2 or 4 or at least 90% identical to SEQ ID NO:1 or 3 (paragraphs 12-14 of the declaration); and ii) Mendlein teaches Gsh1 among a list for spinal cord injury which is listed in a list of different diseases (paragraph 6 of the declaration); transcription factors Nkx6.1, Nkx2.2, which do not show any effect in promoting functional recovery after SCI as evidenced by Exhibits A-C (see paragraphs 7-8 and 10); and the BMS scores in SCI+Gsx1 group showed increased significantly higher than the SCI+control group shown in Exhibit A. This is irrelevant to the issue of nonobviousness of the claimed subject matter and provides no objective evidence thereof. See MPEP § 716.
The statements in the Dr. Cai’s declaration related to other transcription factors Nkx6.1, Nkx2.2 in paragraphs 7-8 and 10 of the declaration are irrelevant to the claimed subject matter because the claimed subject matter is directed to Gsx1 (also called Gsh1).
The declaration and Exhibits A-D also fail to set forth facts that Mendlein teaches a method of treating spinal cord injury via cell therapy using Gsx/Gsh1 and other cited references teach the sequences of Gsx/Gsh1 and Gsx/Gsh-CPP fusion proteins and it is obvious to use the known sequences for Gsx/Gsh1 and Gsx/Gsh-CPP fusion proteins in the method of Mendlein for treating spinal cord injury.
v. While Mendlein, Mutsuga, Bancel, Valerius, Shoemaker and Blaschuk do not explicitly teach a CNS-specific promoter including syn1 promoter, GFAP promoter, nestin promoter, MOBP promoter, MBP promoter, TH promoter or FOXA2 promoter as in claims 7-8 and 10, Chan, Chen, Wulansari and Bujalka teach these limitations and provide motivation and an expectation of success in using a CNS-specific promoter including syn1 promoter, GFAP promoter, nestin promoter, MOBP promoter, MBP promoter, TH promoter or FOXA2 promoter in the method of Mendlein, Shoemaker, Valerius, Bancel, Mutsuga and Blaschuk because syn1 promoter, GFAP promoter, nestin promoter, MOBP promoter, MBP promoter, TH promoter or FOXA2 promoter have been used as a CNS-specific promoter for specific neural lineage targeting and differentiation as taught by Chan, Chen, Wulansari and Bujalka (see p. 1st col., section: plasmids in Chan; see p.173, 1st col., sections 2.1 plasmids and construction of a piggyBac Toolkit in Chen; see p.198, 1st col.- 200,1st col. p.203, 1st col. in Wulansari and see p. 13, 2nd col in Bujalka.
A person of ordinary skill in the art would have recognized that selecting and applying the known CNS-specific promoter including syn1 promoter, GFAP promoter, nestin promoter, MOBP promoter, MBP promoter, TH promoter or FOXA2 promoter and the known technique disclosed by Chan, Chen, Wulansari and Bujalka to the method of Mendlein, Shoemaker, Valerius, Bancel, Mutsuga and Blaschuk would have yielded the predictable result of expressing Gsh1/Gsx1 in specific CNS neural cells including neurons or oligodendrocytes or glial cells and increasing modulation of Gsh1/Gsx1 in increasing the potency of a cell and thereby treating CNS disorders including cerebral stroke, brain trauma, ischemic injury and spinal cord injury in a subject, and resulted in an improved method for treating CNS disorders including cerebral stroke, brain trauma, ischemic injury and spinal cord injury in a subject.
Using the known CNS-specific promoter including syn1 promoter, GFAP promoter, nestin promoter, MOBP promoter, MBP promoter, TH promoter or FOXA2 promoter in the method of Mendlein, Shoemaker, Valerius, Bancel, Mutsuga and Blaschuk would expand application of the method of Mendlein, Shoemaker, Valerius, Bancel, Mutsuga and Blaschuk, and would express and increase the potency of a cell modulated by Gsh1/Gsx1 in specific CNS cells for treating CNS disorders including cerebral stroke, brain trauma, ischemic injury and spinal cord injury, and would also increase patient’s satisfaction with treatment of CNS disorders including cerebral stroke, brain trauma, ischemic injury and spinal cord injury in a subject.
Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to select and apply the known CNS-specific promoter including syn1 promoter, GFAP promoter, nestin promoter, MOBP promoter, MBP promoter, TH promoter or FOXA2 promoter and the known technique disclosed by Chan, Chen, Wulansari and Bujalka to the method of Mendlein, Shoemaker, Valerius, Bancel, Mutsuga and Blaschuk for specific neural lineages or neuronal targeting and differentiation to increase modulation of Gsh1/Gsx1 in increasing the potency of a cell and yield the predictable result of treating CNS disorders including cerebral stroke, brain trauma, ischemic injury and spinal cord injury in a subject.
Accordingly, the rejection of claims 7-8 and 10 under 35 U.S.C. 103 as being unpatentable over Mendlein in view of Mutsuga, Bancel, Valerius, Shoemaker and Blaschuk as applied to claims 1, 3-9, 11, 15-16, 18-19 and 29-33 above, and further in view of Chan, Chen, Wulansari and Bujalka is maintained.
Conclusion
7. NO CLAIM IS ALLOWED.
8. The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
The sequence search results cited in the 103 rejection:
Mutsuga et al. teach that human Gsh1 has a nucleic acid sequence that is 99.9% identical to instant SEQ ID NO:1 (see the sequence alignment below).
SEQ ID NO:1
AB044157
LOCUS AB044157 847 bp mRNA linear PRI 05-JUL-2003
DEFINITION Homo sapiens mRNA for homeobox protein Gsh-1, complete cds.
ACCESSION AB044157
VERSION AB044157.1
KEYWORDS .
SOURCE Homo sapiens (human)
ORGANISM Homo sapiens
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
REFERENCE 1
AUTHORS Mutsuga,N., Iwasaki,Y., Morishita,M., Nomura,A., Yamamori,E.,
Yoshida,M., Asai,M., Ozaki,N., Kambe,F., Seo,H., Oiso,Y. and
Saito,H.
TITLE Homeobox protein Gsh-1-dependent regulation of the rat GHRH gene
promoter
JOURNAL Mol. Endocrinol. 15 (12), 2149-2156 (2001)
PUBMED 11731616
REFERENCE 2 (bases 1 to 847)
AUTHORS Mutsuga,N. and Iwasaki,Y.
TITLE Direct Submission
JOURNAL Submitted (03-JUN-2000) Noriko Mutsuga, Nagoya University School of
Medicine, 1st Department of Internal Medicine; 65 Syouwa Tsurumai,
Nagoya, Aichi 466-8550, Japan (E-mail:nakayamn\@ninds.nih.gov,
Tel:81-744-2142(ex.2142), Fax:81-744-2157)
FEATURES Location/Qualifiers
source 1..847
/organism="Homo sapiens"
/mol_type="mRNA"
/db_xref="taxon:9606"
gene 1..847
/gene="Gsh-1"
5'UTR <1..48
/gene="Gsh-1"
CDS 49..843
/gene="Gsh-1"
/codon_start=1
/product="homeobox protein Gsh-1"
/protein_id="BAB78692.1"
/translation="MPRSFLVDSLVLREAGEKKAPEGSPPPLFPYAVPPPHALHGLSP
GACHARKAGLLCVCPLCVTASQLHGPPGPPALPLLKASFPPFGSQYCHAPLGRQHSAV
SPGVAHGPAAAAAAAALYQTSYPLPDPRQFHCISVDSSSNQLPSSKRMRTAFTSTQLL
ELEREFASNMYLSRLRRIEIATYLNLSEKQVKIWFQNRRVKHKKEGKGSNHRGGGGGG
AGGGGSAPQGCKCASLSSAKCSEDDDELPMSPSSSGKDDRDLTVTP
Query Match 99.8%; Score 845.4; Length 847;
Best Local Similarity 99.9%;
Matches 846; Conservative 0; Mismatches 1; Indels 0; Gaps 0;
Qy 1 GTGGGCGCAGAGGGCGGGCTGGCTGCGGGGCGACCGCGCGCCGGGGCCATGCCGCGCTCC 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 GTGGGCGCAGAGGGCGGGCTGGCTGCGGGGCGACCGCGCGCCGGGGCCATGCCGCGCTCC 60
Qy 61 TTCCTGGTGGACTCGCTAGTGCTGCGCGAGGCGGGCGAGAAGAAGGCGCCCGAGGGCAGC 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 TTCCTGGTGGACTCGCTAGTGCTGCGCGAGGCGGGCGAGAAGAAGGCGCCCGAGGGCAGC 120
Qy 121 CCGCCGCCGCTCTTCCCCTACGCTGTGCCCCCGCCGCACGCGCTGCACGGTCTCTCGCCT 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 CCGCCGCCGCTCTTCCCCTACGCTGTGCCCCCGCCGCACGCGCTGCACGGTCTCTCGCCT 180
Qy 181 GGCGCCTGCCACGCGCGCAAGGCTGGGCTGCTGTGCGTGTGCCCGCTCTGCGTCACCGCC 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 GGCGCCTGCCACGCGCGCAAGGCTGGGCTGCTGTGCGTGTGCCCGCTCTGCGTCACCGCC 240
Qy 241 TCGCAGCTGCATGGGCCCCCCGGGCCGCCCGCGCTGCCTCTACTCAAGGCTTCCTTCCCA 300
||||||||||||||||||||||||||||||||||||||||| ||||||||||||||||||
Db 241 TCGCAGCTGCATGGGCCCCCCGGGCCGCCCGCGCTGCCTCTGCTCAAGGCTTCCTTCCCA 300
Qy 301 CCCTTCGGCTCGCAGTACTGCCACGCGCCCCTGGGCCGCCAGCACTCTGCTGTGTCGCCC 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 CCCTTCGGCTCGCAGTACTGCCACGCGCCCCTGGGCCGCCAGCACTCTGCTGTGTCGCCC 360
Qy 361 GGGGTCGCTCACGGCCCGGCCGCCGCTGCTGCTGCCGCCGCGCTCTACCAGACCTCCTAC 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 GGGGTCGCTCACGGCCCGGCCGCCGCTGCTGCTGCCGCCGCGCTCTACCAGACCTCCTAC 420
Qy 421 CCGCTGCCTGACCCCAGGCAGTTCCACTGCATCTCTGTGGACAGCAGCTCTAACCAGCTG 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 CCGCTGCCTGACCCCAGGCAGTTCCACTGCATCTCTGTGGACAGCAGCTCTAACCAGCTG 480
Qy 481 CCCAGCAGCAAGAGGATGCGCACGGCTTTCACCAGCACGCAGCTGCTAGAGCTGGAGCGC 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 CCCAGCAGCAAGAGGATGCGCACGGCTTTCACCAGCACGCAGCTGCTAGAGCTGGAGCGC 540
Qy 541 GAGTTCGCTTCTAATATGTACCTGTCCCGCCTACGTCGCATCGAGATCGCGACCTACCTG 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 GAGTTCGCTTCTAATATGTACCTGTCCCGCCTACGTCGCATCGAGATCGCGACCTACCTG 600
Qy 601 AATCTGTCCGAGAAGCAGGTGAAGATCTGGTTTCAGAACCGCCGAGTGAAGCACAAGAAG 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 AATCTGTCCGAGAAGCAGGTGAAGATCTGGTTTCAGAACCGCCGAGTGAAGCACAAGAAG 660
Qy 661 GAGGGCAAGGGCAGCAACCATCGTGGCGGCGGCGGCGGGGGTGCCGGTGGTGGCGGGAGC 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 GAGGGCAAGGGCAGCAACCATCGTGGCGGCGGCGGCGGGGGTGCCGGTGGTGGCGGGAGC 720
Qy 721 GCACCGCAAGGCTGCAAGTGCGCATCGCTCTCCTCAGCCAAGTGCTCCGAGGATGACGAC 780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 721 GCACCGCAAGGCTGCAAGTGCGCATCGCTCTCCTCAGCCAAGTGCTCCGAGGATGACGAC 780
Qy 781 GAATTGCCCATGTCTCCGTCCTCCTCAGGGAAGGACGACCGGGATCTTACGGTCACTCCC 840
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 781 GAATTGCCCATGTCTCCGTCCTCCTCAGGGAAGGACGACCGGGATCTTACGGTCACTCCC 840
Qy 841 TAGGCGC 847
|||||||
Db 841 TAGGCGC 847
Bancel et al. (WO2013151670) teach that human Gsh1 has a nucleic acid sequence that is 100% identical to instant SEQ ID NO:1 or has an amino acid sequence that is 100% identical to instant SEQ ID NO:2 (see the sequence alignment below).
SEQ ID NO:1
BAW83985
(NOTE: this sequence has 1 duplicate in the database searched.
See complete list at the end of this report)
ID BAW83985 standard; cDNA; 1663 BP.
XX
AC BAW83985;
XX
DT 05-DEC-2013 (first entry)
XX
DE Protein production-related polynucleotide, SEQ: 810.
XX
KW coding sequence; nanotechnology; protein production; ss.
XX
OS Homo sapiens.
XX
CC PN WO2013151670-A2.
XX
CC PD 10-OCT-2013.
XX
CC PF 09-MAR-2013; 2013WO-US030067.
XX
PR 02-APR-2012; 2012US-0618862P.
PR 02-APR-2012; 2012US-0618866P.
PR 02-APR-2012; 2012US-0618868P.
PR 02-APR-2012; 2012US-0618870P.
PR 02-APR-2012; 2012US-0618873P.
PR 02-APR-2012; 2012US-0618878P.
PR 02-APR-2012; 2012US-0618885P.
PR 02-APR-2012; 2012US-0618896P.
PR 02-APR-2012; 2012US-0618911P.
PR 02-APR-2012; 2012US-0618922P.
PR 02-APR-2012; 2012US-0618935P.
PR 02-APR-2012; 2012US-0618945P.
PR 02-APR-2012; 2012US-0618953P.
PR 02-APR-2012; 2012US-0618957P.
PR 02-APR-2012; 2012US-0618961P.
PR 17-MAY-2012; 2012US-0648244P.
PR 17-MAY-2012; 2012US-0648286P.
PR 05-JUL-2012; 2012US-0668157P.
PR 10-AUG-2012; 2012US-0681645P.
PR 10-AUG-2012; 2012US-0681647P.
PR 10-AUG-2012; 2012US-0681648P.
PR 10-AUG-2012; 2012US-0681649P.
PR 10-AUG-2012; 2012US-0681650P.
PR 10-AUG-2012; 2012US-0681654P.
PR 10-AUG-2012; 2012US-0681658P.
PR 10-AUG-2012; 2012US-0681661P.
PR 10-AUG-2012; 2012US-0681667P.
PR 10-AUG-2012; 2012US-0681675P.
PR 10-AUG-2012; 2012US-0681687P.
PR 10-AUG-2012; 2012US-0681696P.
PR 10-AUG-2012; 2012US-0681704P.
PR 10-AUG-2012; 2012US-0681712P.
PR 10-AUG-2012; 2012US-0681720P.
PR 10-AUG-2012; 2012US-0681742P.
PR 04-SEP-2012; 2012US-0696381P.
PR 03-OCT-2012; 2012US-0709303P.
PR 11-OCT-2012; 2012US-0712490P.
PR 14-DEC-2012; 2012US-0737130P.
PR 14-DEC-2012; 2012US-0737134P.
PR 14-DEC-2012; 2012US-0737135P.
PR 14-DEC-2012; 2012US-0737139P.
PR 14-DEC-2012; 2012US-0737147P.
PR 14-DEC-2012; 2012US-0737152P.
PR 14-DEC-2012; 2012US-0737155P.
PR 14-DEC-2012; 2012US-0737160P.
PR 14-DEC-2012; 2012US-0737168P.
PR 14-DEC-2012; 2012US-0737174P.
PR 14-DEC-2012; 2012US-0737184P.
PR 14-DEC-2012; 2012US-0737191P.
PR 14-DEC-2012; 2012US-0737203P.
PR 14-DEC-2012; 2012US-0737213P.
XX
CC PA (MODE-) MODERNA THERAPEUTICS.
XX
CC PI Bancel S, Chakraborty T, De Fougerolles A, Ejebe K, Elbashir SM;
CC PI Ellsworth JL, Guild J, Hatala P, John M, Roy A, Schrum JP;
CC PI Whoriskey S, Wood KM;
XX
DR WPI; 2013-R06545/70.
XX
CC PT New isolated polynucleotide comprising first region of linked
CC PT nucleosides, first flanking region and second flanking region, used to
CC PT e.g. produce polypeptide of interest e.g. biologics, antibodies and
CC PT vaccines, and treat e.g. diabetes.
XX
CC PS Disclosure; SEQ ID NO 810; 988pp; English.
XX
CC The present invention relates to modified polynucleotides for the
CC production of nuclear proteins. The isolated polynucleotide comprises:
CC (a) a first region of linked nucleosides encoding a polypeptide; (b) a
CC first flanking region comprising a native 5' untranslated region (UTR)
CC (BAW83176-BAW83179) or its functional variants; and (c) a second flanking
CC region comprising (i) a native 3' UTR (BAW83180-BAW83196) or its
CC functional variants, and (ii) a 3' tailing sequence of linked
CC nucleosides. The polynucleotide is useful for producing an increased
CC level of the polypeptide. The isolated polynucleotide (BAW83331-
CC BAW87032), (BAW90735-BAX09329) encodes a polypeptide of (BAW87033-
CC BAW90734) used in the invention.
XX
SQ Sequence 1663 BP; 250 A; 616 C; 455 G; 342 T; 0 U; 0 Other;
Query Match 100.0%; Score 847; Length 1663;
Best Local Similarity 100.0%;
Matches 847; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 GTGGGCGCAGAGGGCGGGCTGGCTGCGGGGCGACCGCGCGCCGGGGCCATGCCGCGCTCC 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 GTGGGCGCAGAGGGCGGGCTGGCTGCGGGGCGACCGCGCGCCGGGGCCATGCCGCGCTCC 60
Qy 61 TTCCTGGTGGACTCGCTAGTGCTGCGCGAGGCGGGCGAGAAGAAGGCGCCCGAGGGCAGC 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 TTCCTGGTGGACTCGCTAGTGCTGCGCGAGGCGGGCGAGAAGAAGGCGCCCGAGGGCAGC 120
Qy 121 CCGCCGCCGCTCTTCCCCTACGCTGTGCCCCCGCCGCACGCGCTGCACGGTCTCTCGCCT 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 CCGCCGCCGCTCTTCCCCTACGCTGTGCCCCCGCCGCACGCGCTGCACGGTCTCTCGCCT 180
Qy 181 GGCGCCTGCCACGCGCGCAAGGCTGGGCTGCTGTGCGTGTGCCCGCTCTGCGTCACCGCC 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 GGCGCCTGCCACGCGCGCAAGGCTGGGCTGCTGTGCGTGTGCCCGCTCTGCGTCACCGCC 240
Qy 241 TCGCAGCTGCATGGGCCCCCCGGGCCGCCCGCGCTGCCTCTACTCAAGGCTTCCTTCCCA 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 TCGCAGCTGCATGGGCCCCCCGGGCCGCCCGCGCTGCCTCTACTCAAGGCTTCCTTCCCA 300
Qy 301 CCCTTCGGCTCGCAGTACTGCCACGCGCCCCTGGGCCGCCAGCACTCTGCTGTGTCGCCC 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 CCCTTCGGCTCGCAGTACTGCCACGCGCCCCTGGGCCGCCAGCACTCTGCTGTGTCGCCC 360
Qy 361 GGGGTCGCTCACGGCCCGGCCGCCGCTGCTGCTGCCGCCGCGCTCTACCAGACCTCCTAC 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 GGGGTCGCTCACGGCCCGGCCGCCGCTGCTGCTGCCGCCGCGCTCTACCAGACCTCCTAC 420
Qy 421 CCGCTGCCTGACCCCAGGCAGTTCCACTGCATCTCTGTGGACAGCAGCTCTAACCAGCTG 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 CCGCTGCCTGACCCCAGGCAGTTCCACTGCATCTCTGTGGACAGCAGCTCTAACCAGCTG 480
Qy 481 CCCAGCAGCAAGAGGATGCGCACGGCTTTCACCAGCACGCAGCTGCTAGAGCTGGAGCGC 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 CCCAGCAGCAAGAGGATGCGCACGGCTTTCACCAGCACGCAGCTGCTAGAGCTGGAGCGC 540
Qy 541 GAGTTCGCTTCTAATATGTACCTGTCCCGCCTACGTCGCATCGAGATCGCGACCTACCTG 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 GAGTTCGCTTCTAATATGTACCTGTCCCGCCTACGTCGCATCGAGATCGCGACCTACCTG 600
Qy 601 AATCTGTCCGAGAAGCAGGTGAAGATCTGGTTTCAGAACCGCCGAGTGAAGCACAAGAAG 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 AATCTGTCCGAGAAGCAGGTGAAGATCTGGTTTCAGAACCGCCGAGTGAAGCACAAGAAG 660
Qy 661 GAGGGCAAGGGCAGCAACCATCGTGGCGGCGGCGGCGGGGGTGCCGGTGGTGGCGGGAGC 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 GAGGGCAAGGGCAGCAACCATCGTGGCGGCGGCGGCGGGGGTGCCGGTGGTGGCGGGAGC 720
Qy 721 GCACCGCAAGGCTGCAAGTGCGCATCGCTCTCCTCAGCCAAGTGCTCCGAGGATGACGAC 780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 721 GCACCGCAAGGCTGCAAGTGCGCATCGCTCTCCTCAGCCAAGTGCTCCGAGGATGACGAC 780
Qy 781 GAATTGCCCATGTCTCCGTCCTCCTCAGGGAAGGACGACCGGGATCTTACGGTCACTCCC 840
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 781 GAATTGCCCATGTCTCCGTCCTCCTCAGGGAAGGACGACCGGGATCTTACGGTCACTCCC 840
Qy 841 TAGGCGC 847
|||||||
Db 841 TAGGCGC 847
SEQ ID NO:2
BAW87687
(NOTE: this sequence has 8 duplicates in the database searched.
See complete list at the end of this report)
ID BAW87687 standard; protein; 264 AA.
XX
AC BAW87687;
XX
DT 05-DEC-2013 (first entry)
XX
DE Protein production-related polypeptide, SEQ: 4512.
XX
KW nanotechnology; protein production.
XX
OS Homo sapiens.
XX
CC PN WO2013151670-A2.
XX
CC PD 10-OCT-2013.
XX
CC PF 09-MAR-2013; 2013WO-US030067.
XX
PR 02-APR-2012; 2012US-0618862P.
PR 02-APR-2012; 2012US-0618866P.
PR 02-APR-2012; 2012US-0618868P.
PR 02-APR-2012; 2012US-0618870P.
PR 02-APR-2012; 2012US-0618873P.
PR 02-APR-2012; 2012US-0618878P.
PR 02-APR-2012; 2012US-0618885P.
PR 02-APR-2012; 2012US-0618896P.
PR 02-APR-2012; 2012US-0618911P.
PR 02-APR-2012; 2012US-0618922P.
PR 02-APR-2012; 2012US-0618935P.
PR 02-APR-2012; 2012US-0618945P.
PR 02-APR-2012; 2012US-0618953P.
PR 02-APR-2012; 2012US-0618957P.
PR 02-APR-2012; 2012US-0618961P.
PR 17-MAY-2012; 2012US-0648244P.
PR 17-MAY-2012; 2012US-0648286P.
PR 05-JUL-2012; 2012US-0668157P.
PR 10-AUG-2012; 2012US-0681645P.
PR 10-AUG-2012; 2012US-0681647P.
PR 10-AUG-2012; 2012US-0681648P.
PR 10-AUG-2012; 2012US-0681649P.
PR 10-AUG-2012; 2012US-0681650P.
PR 10-AUG-2012; 2012US-0681654P.
PR 10-AUG-2012; 2012US-0681658P.
PR 10-AUG-2012; 2012US-0681661P.
PR 10-AUG-2012; 2012US-0681667P.
PR 10-AUG-2012; 2012US-0681675P.
PR 10-AUG-2012; 2012US-0681687P.
PR 10-AUG-2012; 2012US-0681696P.
PR 10-AUG-2012; 2012US-0681704P.
PR 10-AUG-2012; 2012US-0681712P.
PR 10-AUG-2012; 2012US-0681720P.
PR 10-AUG-2012; 2012US-0681742P.
PR 04-SEP-2012; 2012US-0696381P.
PR 03-OCT-2012; 2012US-0709303P.
PR 11-OCT-2012; 2012US-0712490P.
PR 14-DEC-2012; 2012US-0737130P.
PR 14-DEC-2012; 2012US-0737134P.
PR 14-DEC-2012; 2012US-0737135P.
PR 14-DEC-2012; 2012US-0737139P.
PR 14-DEC-2012; 2012US-0737147P.
PR 14-DEC-2012; 2012US-0737152P.
PR 14-DEC-2012; 2012US-0737155P.
PR 14-DEC-2012; 2012US-0737160P.
PR 14-DEC-2012; 2012US-0737168P.
PR 14-DEC-2012; 2012US-0737174P.
PR 14-DEC-2012; 2012US-0737184P.
PR 14-DEC-2012; 2012US-0737191P.
PR 14-DEC-2012; 2012US-0737203P.
PR 14-DEC-2012; 2012US-0737213P.
XX
CC PA (MODE-) MODERNA THERAPEUTICS.
XX
CC PI Bancel S, Chakraborty T, De Fougerolles A, Ejebe K, Elbashir SM;
CC PI Ellsworth JL, Guild J, Hatala P, John M, Roy A, Schrum JP;
CC PI Whoriskey S, Wood KM;
XX
DR WPI; 2013-R06545/70.
XX
CC PT New isolated polynucleotide comprising first region of linked
CC PT nucleosides, first flanking region and second flanking region, used to
CC PT e.g. produce polypeptide of interest e.g. biologics, antibodies and
CC PT vaccines, and treat e.g. diabetes.
XX
CC PS Claim 1; SEQ ID NO 4512; 988pp; English.
XX
CC The present invention relates to modified polynucleotides for the
CC production of nuclear proteins. The isolated polynucleotide comprises:
CC (a) a first region of linked nucleosides encoding a polypeptide; (b) a
CC first flanking region comprising a native 5' untranslated region (UTR)
CC (BAW83176-BAW83179) or its functional variants; and (c) a second flanking
CC region comprising (i) a native 3' UTR (BAW83180-BAW83196) or its
CC functional variants, and (ii) a 3' tailing sequence of linked
CC nucleosides. The polynucleotide is useful for producing an increased
CC level of the polypeptide. The isolated polynucleotide (BAW83331-
CC BAW87032), (BAW90735-BAX09329) encodes a polypeptide of (BAW87033-
CC BAW90734) used in the invention.
XX
SQ Sequence 264 AA;
Query Match 100.0%; Score 1409; Length 264;
Best Local Similarity 100.0%;
Matches 264; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MPRSFLVDSLVLREAGEKKAPEGSPPPLFPYAVPPPHALHGLSPGACHARKAGLLCVCPL 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MPRSFLVDSLVLREAGEKKAPEGSPPPLFPYAVPPPHALHGLSPGACHARKAGLLCVCPL 60
Qy 61 CVTASQLHGPPGPPALPLLKASFPPFGSQYCHAPLGRQHSAVSPGVAHGPAAAAAAAALY 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 CVTASQLHGPPGPPALPLLKASFPPFGSQYCHAPLGRQHSAVSPGVAHGPAAAAAAAALY 120
Qy 121 QTSYPLPDPRQFHCISVDSSSNQLPSSKRMRTAFTSTQLLELEREFASNMYLSRLRRIEI 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 QTSYPLPDPRQFHCISVDSSSNQLPSSKRMRTAFTSTQLLELEREFASNMYLSRLRRIEI 180
Qy 181 ATYLNLSEKQVKIWFQNRRVKHKKEGKGSNHRGGGGGGAGGGGSAPQGCKCASLSSAKCS 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 ATYLNLSEKQVKIWFQNRRVKHKKEGKGSNHRGGGGGGAGGGGSAPQGCKCASLSSAKCS 240
Qy 241 EDDDELPMSPSSSGKDDRDLTVTP 264
||||||||||||||||||||||||
Db 241 EDDDELPMSPSSSGKDDRDLTVTP 264
Valerius et al. teaches that human Gsh1 has an amino acid that is 100% identical to instant SEQ ID NO:4 or has a nucleic acid sequence that is 99.2% identical to instant SEQ ID NO:3 (see the sequence alignment below; p. 339-340, figures 2-3).
SEQ ID NO:4
S63604
homeobox protein Gsh-1 - mouse
C;Species: Mus musculus (house mouse)
C;Date: 28-Oct-1996 #sequence_revision 27-Feb-1997 #text_change 05-Oct-2004
C;Accession: S63604; S66126; A37290; A38809
R;Li, H.; Zeitler, P.S.; Valerius, M.T.; Small, K.; Potter, S.S.
EMBO J. 15, 714-724, 1996
A;Title: Gsh-1, an orphan hox gene, is required for normal pituitary development.
A;Reference number: S63604; MUID:96181350; PMID:8631293
A;Accession: S63604
A;Status: not compared with conceptual translation
A;Molecule type: DNA
A;Residues: 1-261 <LIA>
A;Cross-references: UNIPROT:P31315; UNIPARC:UPI0000023282
R;Valerius, M.T.; Li, H.; Stock, J.L.; Weinstein, M.; Kaur, S.; Singh, G.; Potter, S.S.
Dev. Dyn. 203, 337-351, 1995
A;Title: Gsh-1: A novel murine homeobox gene expressed in the central nervous system.
A;Reference number: S66126; MUID:96172995; PMID:8589431
A;Accession: S66126
A;Status: preliminary
A;Molecule type: mRNA
A;Residues: 1-261 <VAL>
A;Cross-references: UNIPARC:UPI0000023282; EMBL:U21224; NID:g836957; PIDN:AAA96814.1; PID:g836958
R;Singh, G.; Kaur, S.; Stock, J.L.; Jenkins, N.A.; Gilbert, D.J.; Copeland, N.G.; Potter, S.S.
Proc. Natl. Acad. Sci. U.S.A. 88, 10706-10710, 1991
A;Title: Identification of 10 murine homeobox genes.
A;Reference number: A37290; MUID:92073356; PMID:1683707
A;Accession: A37290
A;Status: preliminary
A;Molecule type: DNA
A;Residues: 146-205 <SIN>
A;Cross-references: UNIPARC:UPI000017A2C4
C;Keywords: DNA binding; homeobox; nucleus; transcription regulation
F;147-203/Domain: homeobox homology <HOX>
Query Match 100.0%; Score 1390; Length 261;
Best Local Similarity 100.0%;
Matches 261; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MPRSFLVDSLVLREASDKKAPEGSPPPLFPYAVPPPHALHGLSPGACHARKAGLLCVCPL 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MPRSFLVDSLVLREASDKKAPEGSPPPLFPYAVPPPHALHGLSPGACHARKAGLLCVCPL 60
Qy 61 CVTASQLHGPPGPPALPLLKASFPPFGSQYCHAPLGRQHSVSPGVAHGPAAAAAAAALYQ 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 CVTASQLHGPPGPPALPLLKASFPPFGSQYCHAPLGRQHSVSPGVAHGPAAAAAAAALYQ 120
Qy 121 TSYPLPDPRQFHCISVDSSSNQLPSSKRMRTAFTSTQLLELEREFASNMYLSRLRRIEIA 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 TSYPLPDPRQFHCISVDSSSNQLPSSKRMRTAFTSTQLLELEREFASNMYLSRLRRIEIA 180
Qy 181 TYLNLSEKQVKIWFQNRRVKHKKEGKGSNHRGGAGAGAGGGAPQGCKCSSLSSAKCSEDD 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 TYLNLSEKQVKIWFQNRRVKHKKEGKGSNHRGGAGAGAGGGAPQGCKCSSLSSAKCSEDD 240
Qy 241 DELPMSPSSSGKDDRDLTVTP 261
|||||||||||||||||||||
Db 241 DELPMSPSSSGKDDRDLTVTP 261
SEQ ID NO:3
MMU21224
LOCUS MMU21224 1786 bp mRNA linear ROD 13-APR-1996
DEFINITION Mus musculus homeobox Gsh-1 mRNA, complete cds.
ACCESSION U21224
VERSION U21224.1
KEYWORDS .
SOURCE Mus musculus (house mouse)
ORGANISM Mus musculus
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
Muroidea; Muridae; Murinae; Mus; Mus.
REFERENCE 1 (bases 630 to 809)
AUTHORS Singh,G., Kaur,S., Stock,J.L., Jenkins,N.A., Gilbert,D.J.,
Copeland,N.G. and Potter,S.S.
TITLE Identification of 10 murine homeobox genes
JOURNAL Proc. Natl. Acad. Sci. U.S.A. 88 (23), 10706-10710 (1991)
PUBMED 1683707
REFERENCE 2 (bases 1 to 1786)
AUTHORS Valerius,M.T., Li,H., Stock,J.L., Weinstein,M., Kaur,S., Singh,G.
and Potter,S.S.
TITLE Gsh-1: a novel murine homeobox gene expressed in the central
nervous system
JOURNAL Dev. Dyn. 203 (3), 337-351 (1995)
PUBMED 8589431
REFERENCE 3 (bases 1 to 1786)
AUTHORS Potter,S.S.
TITLE Direct Submission
JOURNAL Submitted (17-FEB-1995) M.Todd Valerius, Basic Science Research,
Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati,
OH 45229-3039, USA
FEATURES Location/Qualifiers
source 1..1786
/organism="Mus musculus"
/mol_type="mRNA"
/strain="NIH Swiss"
/db_xref="taxon:10090"
gene 1..1786
/gene="Gsh-1"
CDS 195..980
/gene="Gsh-1"
/codon_start=1
/product="homeobox protein Gsh-1"
/protein_id="AAA96814.1"
/translation="MPRSFLVDSLVLREASDKKAPEGSPPPLFPYAVPPPHALHGLSP
GACHARKAGLLCVCPLCVTASQLHGPPGPPALPLLKASFPPFGSQYCHAPLGRQHSVS
PGVAHGPAAAAAAAALYQTSYPLPDPRQFHCISVDSSSNQLPSSKRMRTAFTSTQLLE
LEREFASNMYLSRLRRIEIATYLNLSEKQVKIWFQNRRVKHKKEGKGSNHRGGAGAGA
GGGAPQGCKCSSLSSAKCSEDDDELPMSPSSSGKDDRDLTVTP"
regulatory 1760..1765
/regulatory_class="polyA_signal_sequence"
/gene="Gsh-1
Query Match 97.9%; Score 1735; Length 1786;
Best Local Similarity 99.2%;
Matches 1768; Conservative 0; Mismatches 5; Indels 10; Gaps 2;
Qy 1 CCAGCACCTCGCCCGCTCCGGGAGGTGCCCGCAGCAGCAGCCAAGGTGATTCCAGCCCGG 60
|||||||||||| |||||||||||||||||||||||||||||||||||||||||||||||
Db 1 CCAGCACCTCGCGCGCTCCGGGAGGTGCCCGCAGCAGCAGCCAAGGTGATTCCAGCCCGG 60
Qy 61 GCTTGAGCCGCGCGTGGAGCCTCCGGGGCCCGGGAAGCTGCGGGTGGCCGCGGCCAGGGG 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 GCTTGAGCCGCGCGTGGAGCCTCCGGGGCCCGGGAAGCTGCGGGTGGCCGCGGCCAGGGG 120
Qy 121 AAGCTACGACAGGATCTGCAGTTCCCTCGGGCTCCAGGGGCGGGCTGGCGGCAGGTGGAC 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 AAGCTACGACAGGATCTGCAGTTCCCTCGGGCTCCAGGGGCGGGCTGGCGGCAGGTGGAC 180
Qy 181 CGCGCGCCGGAGCCATGCCGCGCTCCTTCCTGGTGGATTCCCTTGTGCTGCGGGAAGCCA 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 CGCGCGCCGGAGCCATGCCGCGCTCCTTCCTGGTGGATTCCCTTGTGCTGCGGGAAGCCA 240
Qy 241 GCGACAAGAAGGCTCCGGAGGGCAGCCCGCCACCGCTCTTCCCCTACGCGGTCCCGCCGC 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 GCGACAAGAAGGCTCCGGAGGGCAGCCCGCCACCGCTCTTCCCCTACGCGGTCCCGCCGC 300
Qy 301 CGCACGCGCTCCACGGCCTCTCGCCGGGCGCCTGCCACGCGCGCAAGGCCGGCTTGCTGT 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 CGCACGCGCTCCACGGCCTCTCGCCGGGCGCCTGCCACGCGCGCAAGGCCGGCTTGCTGT 360
Qy 361 GCGTGTGTCCCCTCTGTGTCACCGCTTCGCAGCTGCACGGGCCCCCCGGGCCGCCGGCAC 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 GCGTGTGTCCCCTCTGTGTCACCGCTTCGCAGCTGCACGGGCCCCCCGGGCCGCCGGCAC 420
Qy 421 TGCCGCTACTCAAGGCGTCCTTCCCTCCCTTCGGATCGCAGTACTGCCACGCACCCCTGG 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 TGCCGCTACTCAAGGCGTCCTTCCCTCCCTTCGGATCGCAGTACTGCCACGCACCCCTGG 480
Qy 481 GCCGCCAGCACTCCGTGTCCCCTGGAGTCGCCCACGGCCCGGCTGCGGCCGCAGCAGCTG 540
||||||||||||||||||||||||||||||||||||||||||| ||||||||||||||||
Db 481 GCCGCCAGCACTCCGTGTCCCCTGGAGTCGCCCACGGCCCGGCCGCGGCCGCAGCAGCTG 540
Qy 541 CTGCACTCTACCAGACCTCCTACCCGCTGCCGGATCCCAGACAGTTTCACTGCATCTCTG 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 CTGCACTCTACCAGACCTCCTACCCGCTGCCGGATCCCAGACAGTTTCACTGCATCTCTG 600
Qy 601 TGGACAGCAGCTCGAACCAGCTGCCCAGCAGCAAGAGGATGCGGACGGCGTTCACCAGCA 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 TGGACAGCAGCTCGAACCAGCTGCCCAGCAGCAAGAGGATGCGGACGGCGTTCACCAGCA 660
Qy 661 CACAGCTCCTGGAGCTGGAGCGAGAGTTCGCCTCCAACATGTACCTCTCCCGCCTGCGGC 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 CACAGCTCCTGGAGCTGGAGCGAGAGTTCGCCTCCAACATGTACCTCTCCCGCCTGCGGC 720
Qy 721 GCATCGAGATCGCGACCTATCTGAACCTGTCCGAGAAGCAGGTGAAGATCTGGTTTCAGA 780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 721 GCATCGAGATCGCGACCTATCTGAACCTGTCCGAGAAGCAGGTGAAGATCTGGTTTCAGA 780
Qy 781 ACCGCCGGGTGAAGCACAAGAAAGAAGGCAAAGGCAGTAACCACCGCGGCGGAGCTGGGG 840
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 781 ACCGCCGGGTGAAGCACAAGAAAGAAGGCAAAGGCAGTAACCACCGCGGCGGAGCTGGGG 840
Qy 841 CGGGGGCCGGCGGGGGCGCACCGCAAGGCTGCAAGTGCTCTTCGCTCTCCTCAGCCAAAT 900
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 841 CGGGGGCCGGCGGGGGCGCACCGCAAGGCTGCAAGTGCTCTTCGCTCTCCTCAGCCAAAT 900
Qy 901 GCTCAGAGGACGACGACGAATTGCCCATGTCTCCATCTTCCTCCGGGAAGGATGACAGAG 960
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 901 GCTCAGAGGACGACGACGAATTGCCCATGTCTCCATCTTCCTCCGGGAAGGATGACAGAG 960
Qy 961 ATCTCACAGTCACTCCGTAGGTGCGCCTTTTAGAGGACCATTGGTTTCCCCA-CCCCCCA 1019
|||||||||||||||||||||||||||||||||||||||||||||||||||| |||||||
Db 961 ATCTCACAGTCACTCCGTAGGTGCGCCTTTTAGAGGACCATTGGTTTCCCCACCCCCCCA 1020
Qy 1020 CCCCGACCCTTCCCGC---------ACTGGTCCCCAGGCACCCGCTGGCCAACCGACGGA 1070
|||||||||||||||| |||| ||||||||||||||||||||||||||||||
Db 1021 CCCCGACCCTTCCCGCACTTCAAAGACTGATCCCCAGGCACCCGCTGGCCAACCGACGGA 1080
Qy 1071 TTTCGTTGGGCTTTGCGGTGGTGCGCAGCTTTAGGCAGAGCTAAGACCTTAGCAGACACT 1130
|||||||||||||||||||||||||||||| |||||||||||||||||||||||||||||
Db 1081 TTTCGTTGGGCTTTGCGGTGGTGCGCAGCTCTAGGCAGAGCTAAGACCTTAGCAGACACT 1140
Qy 1131 TGAAGACAGTGCCCCTGTCCCTTGGGCTTCAGGGTGTTTAGGAGGACTCCAAGCGATGAA 1190
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1141 TGAAGACAGTGCCCCTGTCCCTTGGGCTTCAGGGTGTTTAGGAGGACTCCAAGCGATGAA 1200
Qy 1191 GGCTGAGTCCTCCTCCTAGGACACAGCCTCTTCTCCCAGGCACGCAGGCCGGAGCACAGC 1250
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1201 GGCTGAGTCCTCCTCCTAGGACACAGCCTCTTCTCCCAGGCACGCAGGCCGGAGCACAGC 1260
Qy 1251 GCCTTGCTGACCGCCAGCGCCTCTTCGCCTGCCAACTCTGGGCTGGTTCAAGCTTCCTCG 1310
|||||||||||||||||||||||||||||||||||||||||||||||||||| |||||||
Db 1261 GCCTTGCTGACCGCCAGCGCCTCTTCGCCTGCCAACTCTGGGCTGGTTCAAGTTTCCTCG 1320
Qy 1311 GTTCCACTATTCTCTCCTTCTCGGTCAATCTGGGCTTTTCACTCCGCGAGTGGCTGTTTG 1370
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1321 GTTCCACTATTCTCTCCTTCTCGGTCAATCTGGGCTTTTCACTCCGCGAGTGGCTGTTTG 1380
Qy 1371 CTTTTCTTTTAACATTTCTTTCTTGCCCCCAACTCGTCTCCCCCCACTGTGGTCCTTTAT 1430
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1381 CTTTTCTTTTAACATTTCTTTCTTGCCCCCAACTCGTCTCCCCCCACTGTGGTCCTTTAT 1440
Qy 1431 GCAACACGTCTATGGACTTAACTTTTCCTTCCCTCCTCAGGAAGTCTCTCCCTTCTGTCC 1490
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1441 GCAACACGTCTATGGACTTAACTTTTCCTTCCCTCCTCAGGAAGTCTCTCCCTTCTGTCC 1500
Qy 1491 GTTTGTCCCTTAAACAGGGATCAGGTCTTGCTGTTCGAAGAAGTCCCCCTAGCAGAGAGA 1550
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1501 GTTTGTCCCTTAAACAGGGATCAGGTCTTGCTGTTCGAAGAAGTCCCCCTAGCAGAGAGA 1560
Qy 1551 ACTGTCTCACATGGTATTGTATTGGGGAAAATGACTCTGTTTCCAATACGCTCTAAACCC 1610
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1561 ACTGTCTCACATGGTATTGTATTGGGGAAAATGACTCTGTTTCCAATACGCTCTAAACCC 1620
Qy 1611 CCTTCAAATGAAGCCGCTGTAACCAACCTCTCCCCATTGTCCAGGCCCCGACTCCCTCTG 1670
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1621 CCTTCAAATGAAGCCGCTGTAACCAACCTCTCCCCATTGTCCAGGCCCCGACTCCCTCTG 1680
Qy 1671 GGGACTGACTGACTGTGTCATTGTATCGTCTCTGTAATGCCAGAAGATATTTATTTATTT 1730
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1681 GGGACTGACTGACTGTGTCATTGTATCGTCTCTGTAATGCCAGAAGATATTTATTTATTT 1740
Qy 1731 ATTTATGTACAAAATTTTAAATAAACTTTTTTTTTCTTAGAAA 1773
|||||||||||||||||||||||||||||||||||||||||||
Db 1741 ATTTATGTACAAAATTTTAAATAAACTTTTTTTTTCTTAGAAA 1783
Blaschuk et al. (WO200059939) teach a CPP derived from HIV TAT peptide having the amino acid sequence of instant SEQ ID NO:61 (see the sequence alignment below, p. 16-17; p. 28, claim 4).
SEQ ID NO:61
AAB03932
(NOTE: this sequence has 2058 duplicates in the database searched.
See complete list at the end of this report)
ID AAB03932 standard; peptide; 11 AA.
XX
AC AAB03932;
XX
DT 12-SEP-2003 (revised)
DT 26-FEB-2001 (first entry)
XX
DE TAT protein transduction domain (internalisation moeity).
XX
KW Modulating agent; beta-catenin; hair loss; hair growth; skin;
KW exfoliation; Alzheimer's disease; gene transcription;
KW cell differentiation; hearing loss; inner ear; hyperacusis; tinnitus;
KW hair regeneration.
XX
OS Human immunodeficiency virus; (HIV).
XX
CC PN WO200059939-A1.
XX
CC PD 12-OCT-2000.
XX
CC PF 04-APR-2000; 2000WO-US009174.
XX
PR 05-APR-1999; 99US-00288373.
XX
CC PA (ADHE-) ADHEREX TECHNOLOGIES INC.
XX
CC PI Blaschuk OW, Byers S, Gour BJ;
XX
DR WPI; 2000-679355/66.
XX
CC PT Modulating agents for inhibiting degradation of cytoplasmic beta-catenin,
CC PT used for e.g. stimulating hair growth or reducing hair loss, inhibiting
CC PT development of Alzheimer's disease, comprise internalization moiety and
CC PT amino acid sequence.
XX
CC PS Claim 4; Page 46; 49pp; English.
XX
CC Modulating agents for inhibiting degradation of cytoplasmic beta-catenin
CC are described. The modulating agent comprises an internalisation moiety
CC and one or more of an amino acid sequence SYLDS(PO_4)GIHS(PO_4)G, or a
CC peptide analogue or peptidomimetic of the amino acid sequence. The
CC modulating agents are useful for the manufacture of a medicament for
CC stimulating hair growth or reducing hair loss, stimulating skin
CC exfoliation, and inhibiting the development of Alzheimer's disease. They
CC may also be used to increase the beta-catenin level in a cell, to
CC stimulate activation of gene transcription in a cell, and to stimulate
CC cell differentiation. They may further be used to ameliorate hearing loss
CC resulting from a variety of inner ear disorders, such as hyperacusis and
CC tinnitus, through regeneration of hair cells of the inner ear. (Updated
CC on 12-SEP-2003 to standardise OS field)
XX
SQ Sequence 11 AA;
Query Match 100.0%; Score 58; Length 11;
Best Local Similarity 100.0%;
Matches 11; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 YGRKKRRQRRR 11
|||||||||||
Db 1 YGRKKRRQRRR 11
Bancel et al. (US9050297) teaches a polynucleotide having a nucleic acid sequence that is 100% identical to instant SEQ ID NO:1, a polypeptide having an amino acid sequence that is 100% identical to instant SEQ ID NO:2 (see the sequence alignment below).
SEQ ID NO:1
US-14-106-957-810
(NOTE: this sequence has 3 duplicates in the database searched.
See complete list at the end of this report)
Sequence 810, US/14106957
Patent No. 9050297
GENERAL INFORMATION
APPLICANT: BANCEL, STEPHANE
APPLICANT: CHAKRABORTY, TIRTHA
APPLICANT: DE FOUGEROLLES, ANTONIN
APPLICANT: WHORISKEY, SUSAN
APPLICANT: WEISS, RON
TITLE OF INVENTION: MODIFIED POLYNUCLEOTIDES ENCODING ARYL HYDROCARBON RECEPTOR NUCLEAR TRANSLOCATOR
FILE REFERENCE: M308.10/2030.1308USCON
CURRENT APPLICATION NUMBER: US/14/106,957
CURRENT FILING DATE: 2013-12-16
PRIOR APPLICATION NUMBER: PCT/US2013/030067
PRIOR FILING DATE: 2013-03-09
PRIOR APPLICATION NUMBER: 61/737,213
PRIOR FILING DATE: 2012-12-14
PRIOR APPLICATION NUMBER: 61/737,203
PRIOR FILING DATE: 2012-12-14
PRIOR APPLICATION NUMBER: 61/737,191
PRIOR FILING DATE: 2012-12-14
PRIOR APPLICATION NUMBER: 61/737,184
PRIOR FILING DATE: 2012-12-14
PRIOR APPLICATION NUMBER: 61/737,174
PRIOR FILING DATE: 2012-12-14
PRIOR APPLICATION NUMBER: 61/737,168
PRIOR FILING DATE: 2012-12-14
PRIOR APPLICATION NUMBER: 61/737,160
PRIOR FILING DATE: 2012-12-14
PRIOR APPLICATION NUMBER: 61/737,155
PRIOR FILING DATE: 2012-12-14
PRIOR APPLICATION NUMBER: 61/737,152
PRIOR FILING DATE: 2012-12-14
Remaining Prior Application data removed - See File Wrapper or PALM.
NUMBER OF SEQ ID NOS: 26186
SEQ ID NO 810
LENGTH: 1663
TYPE: DNA
ORGANISM: Homo sapiens
Query Match 100.0%; Score 847; Length 1663;
Best Local Similarity 100.0%;
Matches 847; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 GTGGGCGCAGAGGGCGGGCTGGCTGCGGGGCGACCGCGCGCCGGGGCCATGCCGCGCTCC 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 GTGGGCGCAGAGGGCGGGCTGGCTGCGGGGCGACCGCGCGCCGGGGCCATGCCGCGCTCC 60
Qy 61 TTCCTGGTGGACTCGCTAGTGCTGCGCGAGGCGGGCGAGAAGAAGGCGCCCGAGGGCAGC 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 TTCCTGGTGGACTCGCTAGTGCTGCGCGAGGCGGGCGAGAAGAAGGCGCCCGAGGGCAGC 120
Qy 121 CCGCCGCCGCTCTTCCCCTACGCTGTGCCCCCGCCGCACGCGCTGCACGGTCTCTCGCCT 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 CCGCCGCCGCTCTTCCCCTACGCTGTGCCCCCGCCGCACGCGCTGCACGGTCTCTCGCCT 180
Qy 181 GGCGCCTGCCACGCGCGCAAGGCTGGGCTGCTGTGCGTGTGCCCGCTCTGCGTCACCGCC 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 GGCGCCTGCCACGCGCGCAAGGCTGGGCTGCTGTGCGTGTGCCCGCTCTGCGTCACCGCC 240
Qy 241 TCGCAGCTGCATGGGCCCCCCGGGCCGCCCGCGCTGCCTCTACTCAAGGCTTCCTTCCCA 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 TCGCAGCTGCATGGGCCCCCCGGGCCGCCCGCGCTGCCTCTACTCAAGGCTTCCTTCCCA 300
Qy 301 CCCTTCGGCTCGCAGTACTGCCACGCGCCCCTGGGCCGCCAGCACTCTGCTGTGTCGCCC 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 CCCTTCGGCTCGCAGTACTGCCACGCGCCCCTGGGCCGCCAGCACTCTGCTGTGTCGCCC 360
Qy 361 GGGGTCGCTCACGGCCCGGCCGCCGCTGCTGCTGCCGCCGCGCTCTACCAGACCTCCTAC 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 GGGGTCGCTCACGGCCCGGCCGCCGCTGCTGCTGCCGCCGCGCTCTACCAGACCTCCTAC 420
Qy 421 CCGCTGCCTGACCCCAGGCAGTTCCACTGCATCTCTGTGGACAGCAGCTCTAACCAGCTG 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 CCGCTGCCTGACCCCAGGCAGTTCCACTGCATCTCTGTGGACAGCAGCTCTAACCAGCTG 480
Qy 481 CCCAGCAGCAAGAGGATGCGCACGGCTTTCACCAGCACGCAGCTGCTAGAGCTGGAGCGC 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 CCCAGCAGCAAGAGGATGCGCACGGCTTTCACCAGCACGCAGCTGCTAGAGCTGGAGCGC 540
Qy 541 GAGTTCGCTTCTAATATGTACCTGTCCCGCCTACGTCGCATCGAGATCGCGACCTACCTG 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 GAGTTCGCTTCTAATATGTACCTGTCCCGCCTACGTCGCATCGAGATCGCGACCTACCTG 600
Qy 601 AATCTGTCCGAGAAGCAGGTGAAGATCTGGTTTCAGAACCGCCGAGTGAAGCACAAGAAG 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 AATCTGTCCGAGAAGCAGGTGAAGATCTGGTTTCAGAACCGCCGAGTGAAGCACAAGAAG 660
Qy 661 GAGGGCAAGGGCAGCAACCATCGTGGCGGCGGCGGCGGGGGTGCCGGTGGTGGCGGGAGC 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 GAGGGCAAGGGCAGCAACCATCGTGGCGGCGGCGGCGGGGGTGCCGGTGGTGGCGGGAGC 720
Qy 721 GCACCGCAAGGCTGCAAGTGCGCATCGCTCTCCTCAGCCAAGTGCTCCGAGGATGACGAC 780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 721 GCACCGCAAGGCTGCAAGTGCGCATCGCTCTCCTCAGCCAAGTGCTCCGAGGATGACGAC 780
Qy 781 GAATTGCCCATGTCTCCGTCCTCCTCAGGGAAGGACGACCGGGATCTTACGGTCACTCCC 840
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 781 GAATTGCCCATGTCTCCGTCCTCCTCAGGGAAGGACGACCGGGATCTTACGGTCACTCCC 840
Qy 841 TAGGCGC 847
|||||||
Db 841 TAGGCGC 847
SEQ ID NO:2
US-14-106-957-4512
(NOTE: this sequence has 4 duplicates in the database searched.
See complete list at the end of this report)
Sequence 4512, US/14106957
Patent No. 9050297
GENERAL INFORMATION
APPLICANT: BANCEL, STEPHANE
APPLICANT: CHAKRABORTY, TIRTHA
APPLICANT: DE FOUGEROLLES, ANTONIN
APPLICANT: WHORISKEY, SUSAN
APPLICANT: WEISS, RON
TITLE OF INVENTION: MODIFIED POLYNUCLEOTIDES ENCODING ARYL HYDROCARBON RECEPTOR NUCLEAR TRANSLOCATOR
FILE REFERENCE: M308.10/2030.1308USCON
CURRENT APPLICATION NUMBER: US/14/106,957
CURRENT FILING DATE: 2013-12-16
PRIOR APPLICATION NUMBER: PCT/US2013/030067
PRIOR FILING DATE: 2013-03-09
PRIOR APPLICATION NUMBER: 61/737,213
PRIOR FILING DATE: 2012-12-14
PRIOR APPLICATION NUMBER: 61/737,203
PRIOR FILING DATE: 2012-12-14
PRIOR APPLICATION NUMBER: 61/737,191
PRIOR FILING DATE: 2012-12-14
PRIOR APPLICATION NUMBER: 61/737,184
PRIOR FILING DATE: 2012-12-14
PRIOR APPLICATION NUMBER: 61/737,174
PRIOR FILING DATE: 2012-12-14
PRIOR APPLICATION NUMBER: 61/737,168
PRIOR FILING DATE: 2012-12-14
PRIOR APPLICATION NUMBER: 61/737,160
PRIOR FILING DATE: 2012-12-14
PRIOR APPLICATION NUMBER: 61/737,155
PRIOR FILING DATE: 2012-12-14
PRIOR APPLICATION NUMBER: 61/737,152
PRIOR FILING DATE: 2012-12-14
Remaining Prior Application data removed - See File Wrapper or PALM.
NUMBER OF SEQ ID NOS: 26186
SEQ ID NO 4512
LENGTH: 264
TYPE: PRT
ORGANISM: Homo sapiens
Query Match 100.0%; Score 1409; Length 264;
Best Local Similarity 100.0%;
Matches 264; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MPRSFLVDSLVLREAGEKKAPEGSPPPLFPYAVPPPHALHGLSPGACHARKAGLLCVCPL 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MPRSFLVDSLVLREAGEKKAPEGSPPPLFPYAVPPPHALHGLSPGACHARKAGLLCVCPL 60
Qy 61 CVTASQLHGPPGPPALPLLKASFPPFGSQYCHAPLGRQHSAVSPGVAHGPAAAAAAAALY 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 CVTASQLHGPPGPPALPLLKASFPPFGSQYCHAPLGRQHSAVSPGVAHGPAAAAAAAALY 120
Qy 121 QTSYPLPDPRQFHCISVDSSSNQLPSSKRMRTAFTSTQLLELEREFASNMYLSRLRRIEI 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 QTSYPLPDPRQFHCISVDSSSNQLPSSKRMRTAFTSTQLLELEREFASNMYLSRLRRIEI 180
Qy 181 ATYLNLSEKQVKIWFQNRRVKHKKEGKGSNHRGGGGGGAGGGGSAPQGCKCASLSSAKCS 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 ATYLNLSEKQVKIWFQNRRVKHKKEGKGSNHRGGGGGGAGGGGSAPQGCKCASLSSAKCS 240
Qy 241 EDDDELPMSPSSSGKDDRDLTVTP 264
||||||||||||||||||||||||
Db 241 EDDDELPMSPSSSGKDDRDLTVTP 264
9. THIS ACTION IS MADE FINAL. 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.
10. Any inquiry concerning this communication or earlier communications from the examiner should be directed to Chang-Yu Wang whose telephone number is (571)272-4521. The examiner can normally be reached on Monday-Thursday, 7:00am-5:30pm EST.
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Chang-Yu Wang
December 29, 2025
/CHANG-YU WANG/Primary Examiner, Art Unit 1675