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 .
Applicant’s response to restriction requirement of 11/4/25 is entered.
Claims 1, 4-14, 17, 21-24, 28-33, 36-38, 40-42, and 92-101 remain pending as previously presented.
Election/Restrictions
Applicant’s election without traverse of Group I, as in present Claims 1, 4-13, 32-33, 38, and 92-93 in the reply filed on 11/4/25 is acknowledged.
Claims 14, 17, 21-24, 28-31, 36-37, 40-42, and 93-101 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 11/4/25.
Applicant’s election without traverse of the species of eIF4G, mRNA for a and b, and elections of no IRES or protease site and no trigger, in the reply filed on 17/924,456 is acknowledged. For the record, all species of binding protein that recognizes have been rejoined, as no art was found for eIF4G, therefore, the elected species are considered for this, in the context of mRNAs. Also, per applicant’s request, no IRES, no protease site, and no trigger is required.
Claims 6, 12, and 13 are withdrawn, as being drawn to non-elected species.
Claims 1, 4-5, 7-11, 32-33, 38, and 92-93 are considered with regard to the elected species (RNA and absence of IRES/self-cleavign peptide, and environmental trigger), save where rejections are realized during prosecution, then species may be rejoined, in the interest of compact prosecution.
Claim Objections
Applicant is advised that should claim 1 be found allowable, claim 32 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m). Claim 32 is drawn to the LNP composition Claim 1 but calls it a pharmaceutical composition. Such does not further limit the scope of Claim 1. Thus, the composition claim is of the same substantial scope.
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.
Claim 38 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 38 purports itself to be a “A method of delivering the LNP”, to a cell. However, the claim contains no steps. Thus, it is not clear what is being claimed.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 38 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 38 is to delivering the LNP composition to a cell, but is not limited in its steps.
The specification teaches that for such delivery, the cell must be exposed to the composition (e.g., p. 42, penultimate paragraph). The Art teaches no way to deliver a composition to a cell, other than to contact it with the cell.
Thus, the Artisan would not have understood Applicant to have been in possession of the invention as presently claimed.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims are 1, 4-5, 7-11, 32-33, 38, and 92-93 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claims are generic to “an effector molecule” (it is noted that elements 1 and 2 of part (b) are given the conjunction “and/or” and thus, the effector molecule may always be present for all claims considered herein.
The specification defines “effector molecule” thusly:
Effector Molecule: As used herein, the term “effector molecule” refers to a molecule that can modulate a parameter of, e.g., level and/or activity of: an RNA (e.g., an mRNA); or a protein encoded by the RNA.
(p. 96, paragraph 3).
Therefore, the effector molecule may be any molecule that can be encoded by a polynucleotide (i.e., protein or RNA), that modulates (i.e., increases or decreases) the (i) level of another protein or RNA; or (ii) any activity of any protein or RNA.
In this same paragraph (p. 96, paragraph 3), examples are given for altering mRNA level/activity/subcellular localization, protein level/activity (including half life, and expression), protein translation rate, protein localization, generic examples are given of translation factors, splicing factors, RNA stabilizing factors, RNA editing factors, RNA-binding factors, RNA localization factors, and combinations. This is also taught to include natural, wild type, full length, any fragments, any variants, etc. A specific example is given of eIF4G, which is provided with Table 2. Table 2 provides MS2-binding protein sequences, eIF4G sequences, fusions of these two proteins, PABP, MBP-PABP fusion, TENT4A, MBP-TENT4A fusion, TENT4B, MBP-TENT4B fusion, Gld2, and MBP-Gld2 fusions.
These (the non-eIF4G proteins/fusions) are PABP: poly A binding protein (p. 15), while Gld2, TENT4A and TENT4B are only described as having an ability to “modulate the polyA tail” (p. 79, last paragraph). It is well recognized that Gld2 is a polyA polymerase that adds a polyA tail to mRNAs, that TENT4A and TENT4B are mixed polyA tail nucleotidyltransferase and also is involved in DNA repair.
The brunt of the specification is to the increase in half-life of mRNA containing MBP binding sites (i.e., hairpin loops) in the 3’ UTRs of a second (reporter) mRNA and increased translation efficiency by co-expression of eIF4G fused to MBP, as well as MS2 binding protein fusions to MBP. This is best exemplified by the Examples.
What is not described is the myriad of activities of proteins and RNAs and how to increase or lower them with an encoded effector. What is not described is how they are localized to any specific location. What is not described is why it would be done. For example, mammalian FASN contains seven catalytic domains, each performing distinct activities (e.g., Liu, et al. (2010) “Biochemistry, molecular biology, and pharmacology of fatty acid synthase, an emerging therapeutic target and diagnosis/prognosis marker”, International Journal of Molecular Biology, 1(1): 69-89, pp. 70-71, paragraph bridging pages). There is no description as to what gene(s) should be present as a therapeutic/prophylactic payload, and why they should be used in combination with this as an effector molecule. An RNA effector molecule would be tRNA, and there is no description of which therapeutic/prophylactic payloads would be used with any specific tRNA, or why. Without this info, the effector molecule appears to be a fishing expedition to capture whatever might exist, rather than a description of what and why you are utilizing it.
Given the amazingly-wide variety of proteins and huge number of RNAs, combined with the simple showing of 3’ UTR binding by proteins known to increase mRNA stability translation, the Artisan would not have understood applicant to have been in possession of a generic effector molecule.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 4-5, 7-11, 32-33, 38, and 92-93 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claims are generic for the polypeptide that recognizes the binding element.
The specification teaches that the polypeptide that recognizes the binding element may alter an activity or level of an RNA, i.e., modulates that activity or level (e.g., p. 81, last paragraph).
The specification provides eIF4G, which is provided with Table 2. Table 2 provides MS2-binding protein sequences, eIF4G sequences, fusions of these two proteins, PABP, MBP-PABP fusion, TENT4A, MBP-TENT4A fusion, TENT4B, MBP-TENT4B fusion, Gld2, and MBP-Gld2 fusions.
These (the non-eIF4G proteins/fusions) are PABP: poly A binding protein (p. 15), while Gld2, TENT4A and TENT4B are only described as having an ability to “modulate the polyA tail” (p. 79, last paragraph). It is well recognized that Gld2 is a polyA polymerase that adds a polyA tail to mRNAs, that TENT4A and TENT4B are mixed polyA tail nucleotidyltransferase and also is involved in DNA repair.
The brunt of the specification is to the increase in half-life of mRNA containing MBP binding sites (i.e., hairpin loops) in the 3’ UTRs of a second (reporter) mRNA and increased translation efficiency by co-expression of eIF4G fused to MBP, as well as MS2 binding protein fusions to MBP. This is best exemplified by the Examples.
All of these molecules bind to the binding element, thereby stabilizing and increasing half life and transcription from the RNA containing the binding element. There is no teaching of molecules that decrease half life or cause decreased translation of the mRNA. AUF1 is a known protein that targets mRNA for degradation (e.g., Chenette, et al. (2016) “Targeted mRNA Decay by RNA Binding Protein AUF1 Regulates Adult Muscle Stem Cell Fate, Promoting Skeletal Muscle Integrity”, Cell Reports, 16: 1379-1390, TITLE).
For these types of RNA binding proteins, no expression of the transgene would be expected, as it would be degraded.
Thus, given the wide variety of RNA binding proteins, and the limited showing of proteins that increase half life and expression, the Artisan would not have understood Applicant to have been in possession of the scope of the modulations claimed.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ROBERT M KELLY whose telephone number is (571)272-0729. The examiner can normally be reached M-F: 8a-5p.
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ROBERT M. KELLY
Examiner
Art Unit 1638
/ROBERT M KELLY/Primary Examiner, Art Unit 1638