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
Request for Continued Examination
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 03/26/2026 has been entered.
Status of Application/Amendment/Claims
Applicant's response filed 03/26/2026 has been considered. Rejections and/or objections not reiterated from the previous office action mailed 12/04/2025 are hereby withdrawn. The following rejections and/or objections are either newly applied or are reiterated and are the only rejections and/or objections presently applied to the instant application. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
With entry of the amendment filed on 03/26/2026, claims 1-3 and 5-10 are pending in the application.
Claims 8-10 are new claims and under examination.
The amendment to the Abstract has been entered.
The Double Patenting rejections are maintained and updated due to new claim limitations.
New Claim Rejections
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(1), 5(1), 6(1) and 7(1) are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention.
The claims recite "an oligonucleotide" and this is indefinite because oligonucleotide is not specifically defined in the specification however in [0016] an oligonucleotide is referred to as a gapmer oligonucleotide and in [0028] an oligonucleotide can be a probe or primer and in claim 1 the oligonucleotide can be an antisense oligonucleotide. Thus it is unclear what type of oligonucleotide is represented in the claims.
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. See 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);and, 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 a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this 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 §§ 706.02(l)(1) - 706.02(l)(3) 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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/forms/. The 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 http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1-3 and 5-10 are rejected under the judicially created doctrine of obviousness-type double patenting as being unpatentable over claims 1-9 and 15 of U.S. Application No. 17,997,138 (APP138) in view of Galderisi et al. ("Antisense oligonucleotides as therapeutic agents." Journal of cellular physiology 181.2 (1999): 251-257) and Dias et al. ("Antisense oligonucleotides: basic concepts and mechanisms." Molecular cancer therapeutics 1.5 (2002): 347-355). Although the conflicting claims are not identical, they are not patentably distinct from each other because the instant claims and the claims of the patent are drawn to patently indistinguishable subject matter
MPEP 804 “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 determining whether a nonstatutory basis exists for a double patenting rejection, the first question to be asked is: Is any invention claimed in the application anticipated by, or an obvious variation of, an invention claimed in the patent? If the answer is yes, then a nonstatutory double patenting rejection may be appropriate.”
“The specification can be used as a dictionary to learn the meaning of a term in the claim. Toro Co. v. White Consol. Indus., Inc., 199 F.3d 1295, 1299, 53 USPQ2d 1065, 1067 (Fed. Cir. 1999) ("[W]ords in patent claims are given their ordinary meaning in the usage of the field of the invention, unless the text of the patent makes clear that a word was used with a special meaning.")”. MEX3B is defined in the specification as a protein known to be a molecule that binds to mRNAs such as inflammatory cytokines and chemokines to affect their function and teach the function of these inflammatory cytokines and chemokines are involved in serious diseases such as asthma and cancer (pages 1-2).
The claims of APP138 are drawn to a prophylactic or therapeutic method for treating a disease comprising administering an inhibitor of MEX3B such as an inhibitor nucleic acid. The instant claims are drawn to an inhibitor nucleic acid targeted to MEX3B and to a prophylactic or therapeutic method for treating disease comprising administering an inhibitor of MEX3B. Thus, the instant claims and claims of APP138 are not drawn to patentably distinct inventions.
It would have been obvious to use the instant antisense oligonucleotide targeted to MEX3B in the methods a prophylactic or therapeutic method for treating a disease given the claims of APP138 are drawn to treating the disease by inhibition of MEX3B expression and given MEX3B is defined as binding to mRNAs such as inflammatory cytokines and chemokines, involved in serious diseases, to affect their function. Galderisi et al. teach antisense oligonucleotides can block expression of specific target genes involved in the development of human diseases (abstract) and the use of these antisense oligonucleotides as selective inhibitors of gene expression offers a rational approach for the treatment of gene-mediated disorders (page 252 first para.). Galderisi et al. teach antisense oligonucleotides have already shown their effectiveness in several preclinical studies (see page 255 last para.). Dias et al. teach antisense oligonucleotide reduction in target RNA expression can be quite efficient, reaching 80-95% down-regulation of mRNA expression (see page 349 last para.) Thus it would have been obvious to use the instant claims in the method of APP 138 with an expectation of downregulation by 60% or even a third or less of the target gene.
Claims 1-3 and 5-10 are rejected under the judicially created doctrine of obviousness-type double patenting as being unpatentable over claim 1 of U.S. Patent No. 11,312,956 (PAT956) in view of Galderisi et al. ("Antisense oligonucleotides as therapeutic agents." Journal of cellular physiology 181.2 (1999): 251-257) and Dias et al. ("Antisense oligonucleotides: basic concepts and mechanisms." Molecular cancer therapeutics 1.5 (2002): 347-355Although the conflicting claims are not identical, they are not patentably distinct from each other because the instant claims and the claims of the patent are drawn to patently indistinguishable subject matter
MPEP 804 “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 determining whether a nonstatutory basis exists for a double patenting rejection, the first question to be asked is: Is any invention claimed in the application anticipated by, or an obvious variation of, an invention claimed in the patent? If the answer is yes, then a nonstatutory double patenting rejection may be appropriate.”
“The specification can be used as a dictionary to learn the meaning of a term in the claim. Toro Co. v. White Consol. Indus., Inc., 199 F.3d 1295, 1299, 53 USPQ2d 1065, 1067 (Fed. Cir. 1999) ("[W]ords in patent claims are given their ordinary meaning in the usage of the field of the invention, unless the text of the patent makes clear that a word was used with a special meaning.")”. MEX3B is defined in the specification as a protein known to be a molecule that binds to mRNAs such as inflammatory cytokines and chemokines to affect their function and teach the function of these inflammatory cytokines and chemokines are involved in serious diseases such as asthma and cancer (pages 1-2).
The claims of PAT956 are drawn to a method of inhibiting expression of MEX3B for treating disease comprising administering an antisense oligonucleotide targeted to an exon of the MEX3B gene. The instant claims are drawn to an inhibitor nucleic acid targeted to MEX3B and to a prophylactic or therapeutic method for treating disease comprising administering an inhibitor of MEX3B. Thus, the instant claims and claims of PAT956 are not drawn to patentably distinct inventions.
It would have been obvious to use the instant antisense oligonucleotide targeted to MEX3B in the methods for treating a disease given the claims of PAT956 are drawn to treating the disease by inhibition of MEX3B expression and given MEX3B is defined as binding to mRNAs such as inflammatory cytokines and chemokines, involved in serious diseases, to affect their function. Galderisi et al. teach antisense oligonucleotides can block expression of specific target genes involved in the development of human diseases (abstract) and the use of these antisense oligonucleotides as selective inhibitors of gene expression offers a rational approach for the treatment of gene-mediated disorders (page 252 first para.). Galderisi et al. teach antisense oligonucleotides have already shown their effectiveness in several preclinical studies (see page 255 last para.). Dias et al. teach antisense oligonucleotide reduction in target RNA expression can be quite efficient, reaching 80-95% down-regulation of mRNA expression (see page 349 last para.) Thus it would have been obvious to use the instant claims in the method of PAT956 with an expectation of downregulation by 60% or even a third or less of the target gene.
Moreover, the Court of Appeals for the Federal Circuit in Pfizer Inc, v Teva pharmaceuticals USA Inc., 86 USPQ2d 1001 at page 1008 (March 2008), indicated that there is no patentable distinction between claims to a product and a method of using that product disclosed in the specification of the application.
Claims 1-3 and 5-10 are rejected under the judicially created doctrine of obviousness-type double patenting as being unpatentable over claims 1-4 of U.S. Patent No. 11,279,935 (PAT935) in view of Galderisi et al. ("Antisense oligonucleotides as therapeutic agents." Journal of cellular physiology 181.2 (1999): 251-257) and Dias et al. ("Antisense oligonucleotides: basic concepts and mechanisms." Molecular cancer therapeutics 1.5 (2002): 347-355). Although the conflicting claims are not identical, they are not patentably distinct from each other because the instant claims and the claims of the patent are drawn to patently indistinguishable subject matter
MPEP 804 “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 determining whether a nonstatutory basis exists for a double patenting rejection, the first question to be asked is: Is any invention claimed in the application anticipated by, or an obvious variation of, an invention claimed in the patent? If the answer is yes, then a nonstatutory double patenting rejection may be appropriate.”
“The specification can be used as a dictionary to learn the meaning of a term in the claim. Toro Co. v. White Consol. Indus., Inc., 199 F.3d 1295, 1299, 53 USPQ2d 1065, 1067 (Fed. Cir. 1999) ("[W]ords in patent claims are given their ordinary meaning in the usage of the field of the invention, unless the text of the patent makes clear that a word was used with a special meaning.")”. MEX3B is defined in the specification as a protein known to be a molecule that binds to mRNAs such as inflammatory cytokines and chemokines to affect their function and teach the function of these inflammatory cytokines and chemokines are involved in serious diseases such as asthma and cancer (pages 1-2).
The claims of PAT935 are drawn to method of inhibiting expression of MEX3B for treating a respiratory or pulmonary disease comprising administering an antisense inhibitor nucleic acid. The instant claims are drawn to therapeutic method for treating disease comprising administering an inhibitor of MEX3B. Thus, the instant claims and claims of PAT935 are not drawn to patentably distinct inventions.
It would have been obvious to use the instant antisense oligonucleotide targeted to MEX3B in the methods for treating a disease given the claims of PAT935 are drawn to treating the disease by inhibition of MEX3B expression and given MEX3B is defined as binding to mRNAs such as inflammatory cytokines and chemokines, involved in serious diseases, to affect their function. Galderisi et al. teach antisense oligonucleotides can block expression of specific target genes involved in the development of human diseases (abstract) and the use of these antisense oligonucleotides as selective inhibitors of gene expression offers a rational approach for the treatment of gene-mediated disorders (page 252 first para.). Galderisi et al. teach antisense oligonucleotides have already shown their effectiveness in several preclinical studies (see page 255 last para.). Dias et al. teach antisense oligonucleotide reduction in target RNA expression can be quite efficient, reaching 80-95% down-regulation of mRNA expression (see page 349 last para.) Thus it would have been obvious to use the instant claims in the method of PAT935 with an expectation of downregulation by 60% or even a third or less of the target gene.
Moreover, the Court of Appeals for the Federal Circuit in Pfizer Inc, v Teva pharmaceuticals USA Inc., 86 USPQ2d 1001 at page 1008 (March 2008), indicated that there is no patentable distinction between claims to a product and a method of using that product disclosed in the specification of the application.
Response to Arguments and Amendments
Applicant argues the instant claims have been amended to refer to wherein the nucleic acid reduces expression of a MEX3B gene by 60% or more, as compared with a negative control oligonucleotide consisting of the nucleotide sequence set forth in SEQ ID NO: 10.” Such “nucleic acid reduces expression of a MEX3B gene by 60% or more, as compared with a negative control oligonucleotide consisting of the nucleotide sequence set forth in SEQ ID NO: 10” is not disclosed in Claims 1 to 15 of the US application US17/997,138, 11,312,956 or 11,279,935 and thus differs therefrom.
This argument is not persuasive because the Double Patenting rejection is an obvious-type rejection and as stated above, claims of US17/997,138, 11,312,956 or 11,279,935 are drawn to methods of treatment using an antisense that reduced expression of MEX3B and it would have been obvious to use this antisense in the claimed methods. One of skill in the art would have expected the antisense to reduce expression of the MEX3B so the new claim limitations would have been obvious.
MPEP 804 states that a nonstatutory Double Patenting rejection, if not based on an anticipation rationale, is analogous to the nonobviousness requirement of 35 U.S.C. 103 and although the co-pending or patent disclosures is not considered prior art, it may still be used to interpret the applied claims. Thus as stated above in the rejections, Galderisi et al. teach antisense oligonucleotides can block expression of specific target genes involved in the development of human diseases (abstract) and the use of these antisense oligonucleotides as selective inhibitors of gene expression offers a rational approach for the treatment of gene-mediated disorders (page 252 first para.). Galderisi et al. teach antisense oligonucleotides have already shown their effectiveness in several preclinical studies (see page 255 last para.). Dias et al. teach antisense oligonucleotide reduction in target RNA expression can be quite efficient, reaching 80-95% down-regulation of mRNA expression (see page 349 last para.) Thus it would have been obvious to use the instant claims in the method of the co-pending Applications and Patents with an expectation of downregulation by 60% or even a third or less of the target gene.
Applicant then argues the present inventors comprehensively performed Gapmer screening walking for MEX3B gene expression inhibition using gapmers targeting the MEX3B gene, for the entire DNA sequence of the MEX3B gene. As a result, within such hmrGD-87~93, the gapmer-type nucleic acid hmrGD-89 (SEQ ID NO: 2) and gapmer-type nucleic acid hmrGD-89-2 (SEQ ID NO: 1) possessing an expression inhibiting effect were unexpectedly discovered, and moreover, the expression inhibiting effect thereof far exceeded hmrGD-176~203. This argument is not persuasive because the claims of US17/997,138, 11,312,956 or 11,279,935 do not recite sequences or specific antisense oligonucleotides with any percent reduction of inhibition. Limitations in the specification cannot be imported into the claims. Thus based on the nonobviousness Double Patenting rejections above, it would have been obvious to use the instant claims in the method of the co-pending Applications and Patents with an expectation of downregulation by 60% or even a third or less of the target gene.
The rejections are therefore proper.
Closest prior art
The closest prior art for claimed SEQ ID Nos.1, 2 and 3 is Bentwich et al. (Patent 7250496) and Feng et al. (Patent 11,905,521) cited in O.A. mailed 04/10/2025 wherein the alignments were illustrated on pages 9-11. The prior art teach sequences 21-24 nucleotides in length comprising the claimed SEQ ID Nos. The prior art does not teach antisense oligonucleotide sequences consisting of SEQ ID Nos.1, 2 and 3 which are 16, 16 and 14 nucleotides in length, respectively.
The prior art of Yamazumi et al. ("The RNA binding protein Mex-3B is required for IL-33 induction in the development of allergic airway inflammation." Cell Reports 16.9 (2016): 2456-2471 of record cited on IDS filed 03/30/2022) MEX3B expression is related to allergic airway inflammation (see page 2457 col. 1) teach siRNA and a locked nucleic acid targeted to MEX3B that suppressed the development of airway inflammation (see page 2463 last para to 2464). Yamazumi et al. does not describe antisense oligonucleotides 14-16 nucleotides in length or a motivation to make antisense oligonucleotides from the siRNA or LNA as described.
The MEX3B complete coding sequence is known in the art as GenBank AY950678 and while methods of designing antisense oligonucleotides are known in the art, Sciabola et al. ("PFRED: A computational platform for siRNA and antisense oligonucleotides design." PLoS One 16.1 (2021)) teach known methods and algorithms for designing antisense oligonucleotides can be logistically challenging given there are many design criteria that can be incorporated into the selection tool or therapeutic sequences and describes numerous different computational tools to address different aspects of the design process (page 2). Thus nothing in the known methods and algorithms for designing antisense oligonucleotides taught in Sciabola et al. would lead one of skill in the art to a predictable computational tool to design an antisense sequences targeted to MEX3B.
There is no motivation for one of skill in the art to identify any specific region of the MEX3B gene to target, then choose any of the computational tools to design the claimed antisense sequences and then choose specific modified nucleotides and internucleotide linkages, from the vast amount of known modified nucleotides and linkages, to arrive at the claimed antisense oligonucleotide. Furthermore there is not a design need or market demand to design the claimed antisense to MEX3B. As taught by Yamazumi et al., inhalation of LNA targeted to MEX3B decreased allergic airway inflammation in mice and there would not have been a reason to use a completely different antisense oligonucleotide to try and inhibit MEX3B or a reason to use make this antisense oligonucleotide to treat airway inflammation such as asthma. Lastly there is not a finite number of identified and predictable solutions to make it obvious to try making the antisense targeted to MEX3B given a target region has not been identified. (MPEP 2143 KSR International Co. v. Teleflex Inc., 550 U.S. 398 (2007)).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Kimberly Chong at (571)272-3111. The examiner can normally be reached Monday thru Friday between M-F 8:00am-4:30pm.
If attempts to reach the examiner by telephone are unsuccessful please contact the SPE for 1636 Neil Hammell at 571-272-5919. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KIMBERLY CHONG/
Primary Examiner Art Unit 1636
Prosecution Insights