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 .
Election/Restrictions
Applicant’s election without traverse of methods comprising contacting a hexanucleotide repeat expansion RNA r(G4C2) exp with an ALS compound comprising a pyridocarbazole moiety bound to an RNase moiety in Formula I in the reply filed on 2026 July 07 is acknowledged. Due to the election, a search of claims 1-12, 18-20, and 27 has been performed.
Claim Objections
Claims 1, 10, 11, and 27 objected to because of the following informalities:
Claims 1 states “with an ALS compound”, should state “with an Amyotrophic lateral sclerosis (ALS) compound”
Claim 10 states “c9 iPSCs cells”, should state “c9 iPSCs”
Claim 11 states “the cells are c9ALS/FTD”, should state “the cells are c9ALS/Frontotemporal Dementia (FTD)”
Claim 27 should have a “,” after “-CH2-O- “
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1, 4, 10, 11, 20, and 27 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 1 states “A method comprising contacting a hexanucleotide repeat expansion”, and the term “contacting” is determined to be indefinite. The specification does not define the term “contacting” and it is unclear if contacting is defined as binding/complexing or sequestration/translation of RNA. The examiner is interpreting the term “contacting” as encompassing binding/complexing and sequestration/translation, for purposes of applying prior art.
Regarding Claims 1, 20, and 27, the claims use the term “preferably” when referring to substituents in Formula I. “Preferably” is determined to be exemplary language, and is indefinite, because the intended scope of the claim is unclear.
Claim 4 states “The method according to claim 1 wherein r(G4C2) m is an abnormal number of repeats with m being at least 20-1000.”, and this is determined to be indefinite. It is unclear if “at least” extends to 1000, or if 1000 is the upper limit of the claim.
Claim 4 recites the limitation “The method according to claim 1 wherein r(G4C2) m is an abnormal number of repeats with m being at least 20-1000.” Claim 1 does not define r(G4C2) with m as the variable, only “exp” as the variable. There is insufficient antecedent basis for this limitation in the claim.
Claim 10 states “The method according to claim 9 wherein the cells are HEK293T cells, patient-derived lymphoblastoid cells, induced pluripotent stem cells (c9 iPSCs cells), iPSC- derived spinal neurons (c9 iPSNs).”, and it is unclear if all of the cells need to be included, that are listed in the claim, or if any one of the listed cells are included. Examiner suggests that the applicant add an “and” or an “or” between the different kinds of cells when listing them. The claim is currently being interpretated as any one of the cell lines that could meet the limitations of Claim 10.
Regarding claim 10, the phrase "induced pluripotent stem cells" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). It is unclear if the claims are limited to iPSC cells in general or specifically limited to c9 iPSCs cells, because it is unclear if the phrase within the parenthesis is part of the claimed invention or meant to limit the claim.
Regarding claim 10, the phrase "iPSC-derived spinal neurons" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). It is unclear if the claims are limited to iPSC-derived spinal neurons in general or specifically limited to c9 iPSNs, because it is unclear if the phrase within the parenthesis is part of the claimed invention or meant to limit the claim.
Claim 11 states “The method according to claim 10 wherein the cells are c9ALS/FTD BAC cells in a transgenic mouse model.”, but it is unclear if c9ALS/FTD BAC cells are a type of cell listed in Claim 10, what category do they fall into. The specification does not provide clarity on whether or not c9ALS/FTD cells are HEK293T cells, patient-derived lymphoblastoid cells, induced pluripotent stem cells (c9 iPSCs cells), or iPSC- derived spinal neurons (c9 iPSNs).
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 4 and 11 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 4 states “The method according to claim 1 wherein r(G4C2)m is an abnormal number of repeats with m being at least 20-1000”, but claim 1 does not define r(G4C2) with m as the variable, only “exp” as the variable. Therefore, claim 4 is not further limit Claim 1, from which it depends.
Claim 11 states “The method according to claim 10 wherein the cells are c9ALS/FTD BAC cells in a transgenic mouse model.” but claim 10 states that “wherein the cells are HEK293T cells, patient-derived lymphoblastoid cells, induced pluripotent stem cells (c9 iPSCs cells), iPSC- derived spinal neurons (c9 iPSNs)”. The claim is interpreted as “c9ALS/FTD BAC cells” are not a type of cell listed in Claim 10 and therefore do not further narrow.
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.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-12, 18-20, and 27 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 5-8, 10-20, 22, 23, 26, 27, and 34 of copending Application No. 18/032,648 in view of Paranjpe (Ameya Paranjpe et al., “Disulfiram Compositions and Treatments for Brain Tumors”, WO 2015120254 A1, Pub. Date: August 13, 2015), Barillari (Caterina Barillari et al., “Classical Bioisosteres”, Bioisosteres in Medicinal Chemistry, First Edition, Pgs. 15-29, Pub. Date: 2012), and Li (Z. Lane Li et al. “Relationship Between Physical Properties and Crystal Structures of Chiral Drugs”, Journal of Pharmaceutical Sciences,Volume 86, Number 10, Pub. Date October 1997, Pgs. 1073-1078).
Regarding instant Claims 1 and 27, Claim 1 in copending application ‘648 teaches “A method comprising contacting a hexanucleotide repeat expansion RNA r(G4C2)exp with an ALS, wherein the ALS compound is a bridged dimer of Formula II:
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479
693
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Wherein:
a is an integer of 1 to 5:
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589
734
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Copending Application ‘648 does not teach the same pyridocarbazole small molecule as in instant Formula I.
Paranjpe discloses compound sobuzoxane, a small pyridocarbazole molecule below, as a compound administered for inhibiting 06-methylguanine DNA methyltransferase in human brain tumor cells (Abstract, and Claim 10).
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393
505
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Compound sobuzoxane disclosed in Paranjpe overlaps with the right side of the moiety in instant Formula (I). To map sobuzoxane, with the right side of the moiety in Formula I, R is a C1 alkyl group.
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238
289
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[AltContent: oval]Paranjpe does not disclose a methyl group attached to sobuzoxane, or the associated stereochemistry.
Barillari discloses bioisosterism is a term used to describe structurally related substances with similar antagonistic biological properties. Barillari discloses that -CH3 and -H are classical isosteres, because they both are monovalent groups (Pg. 17). Monovalent atoms/groups are chemical species that have a valency of one.
Barillari does not disclose a motivation for adding stereochemistry to a compound.
Li teaches pharmaceutical applications of enantiomers of chiral drugs, and that different
enantiomers produce different pharmacological and toxicological effects when they interact with
biological macromolecules (Pg. 1073, Introduction).
Regarding instant Claims 1-12, 18-20, and 27, it would have been prima facie obvious, for one of ordinary skill in the art, to optimize the pyridocarbazole small molecule, sobuzoxane, disclosed in Paranjpe, by substituting hydrogen for a methyl group, and adding stereochemistry, because Barillari teaches hydrogen and methyl groups are bioisosteres with similar structures and biological activity, and Li teaches different enantiomers produce different pharmacological and toxicological effects. It would have been obvious to try a finite number of enantiomers for sobuzoxane and through routine optimization, determine which one produces the least toxicological effects with the greatest pharmacological effects, to arrive at a compound of instant Formula I because routine optimization is known in the art. One of ordinary skill would be motivated to substitute modified sobuzoxane into Formula II of copending application ‘648 to arrive at a compound of instant Formula I, because Formula II in copending application ‘648 and sobuzoxane are both pyridocarbazole small molecules. One of ordinary skill would be motivated to substitute one pyridocarbazole small molecule for another to arrive at instant Formula I because both compounds are administered for treating brain diseases/disorders, such as ALS and brain cancer. Two compounds of the same class, pyridocarbazole small molecules, used to treat disorders/diseases of the same organ, the brain, would motivate someone of ordinary skill to substitute one for the other with a reasonable expectation for success.
This is a provisional nonstatutory double patenting rejection.
Closest Prior Art
The closest prior art is Su (Zhaoming Su et al., “Discovery of a Biomarker and Lead Small Molecules to Target r(GGGGCC)-Associated Defects in c9FTD/ALS”, Neuron Report, Volume 83, Pgs. 1043-1050, Pub. Date: September 3, 2014), Paranjpe (Ameya Paranjpe et al., “Disulfiram Compositions and Treatments for Brain Tumors”, WO 2015120254 A1, Pub. Date: August 13, 2015) and Costales (Matthew G. Costales et al., “Small-molecule targeted recruitment of a nuclease to cleave an oncogenic RNA in a mouse model of metastatic cancer”, PNAS, Pgs. 2406-2411, Pub. Date: February 4, 2020, as cited on the IDS dated 07/07/2026).
Instant Formula I
[AltContent: textbox (ALS pyridocarbazole)]
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199
411
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Costales
RIBOTAC
Paranjpe
Pyridocarbazole
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151
284
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174
222
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Su
Pyridocarbazole small molecules
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199
387
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While the prior art teaches the RNArG4C2exp moiety (see Table above, dark gray dashed box), a structurally similar pyridocarbazole (see Table above, black rectangle), and a linker (see
Table above, light gray rectangle) as in instant Formula I, it would not have been obvious to an artisan to arrive at the instant compound because:
i) modifying the pyridocarbazole of Paranje would require a change in H for Me and a stereochemical alteration, either of which might individually be obvious to a skilled artisan but no reasonable suggestion or motivation was found to make both;
ii) modifying the RIBOTAC of Costales to include the pyridocarbazole of Paranje would not have been obvious to an artisan, there is no reasonable suggestion or motivation to make the required substitution; and
iii) modifying the method disclosed in Su for pyridocarbazole small molecules targeting repeat expansion C9ORF72 caused by c9FTD/ALS, by substituting the modified RIBOTAC of Costales and Paranje is not obvious, there is no motivation nor suggestion in the prior art to modify or substitute as required.
Therefore, while the different prior art references individually teach the elements required by the instant claims, as discussed above, there is no motivation or suggestion in the prior art to make all of the required modifications necessary to render obvious the claimed invention.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CIERRA M ROCHELLE whose telephone number is (571)272-9962. The examiner can normally be reached Mon-Fri 8:00-5:00 EST.
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/C.M.R./Examiner, Art Unit 1627
/JENNIFER A BERRIOS/Primary Examiner, Art Unit 1613
Prosecution Insights