DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Status
Claims 1-4, 6, 12, 20, 27, 32-35, 37, 39-40 and 45- 47 are pending.
Claims 1-4, 6, 12, 20, and 27 have been considered on the merits.
Claims 32-35, 37, 39-40 and 45-47 are withdrawn.
Claims 5, 7- 11, 13- 19, 21-26, 28-31, 36, 38, 41-44, and 48-51 are canceled.
Claims 1 and 40 are objected.
Claims 1-4, 6, 12, 20, and 27 are rejected.
No claims are allowed.
Continued Examination Under 37 CFR 1.114
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 Nov 13, 2025 has been entered.
Election/Restrictions
Claims 32-35, 37, 39-40 and 45-47 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention/species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 6/21/2024.
Applicant’s election without traverse of Group I, claims 1-4, 6-7, 11-12, 20, and 27, and species of nucleic acid sequence of SEQ ID NO: 38 and the chemical modification of 2'-O-methyl 3'phosphorothioate (MS) in the reply filed on June 21, 2024 is acknowledged.
The multiple SEQ ID Nos listed in Claim 1 is interpreted by this examiner as being a Markush claim. Furthermore, Claim 1 has been amended to exclude the elected species of the Markush claim (SEQ ID No 38 withdrawn from consideration). Therefore, “examination will be extended to the extent necessary to determine patentability of the Markush claim (see MPEP 803.02.III.A).” In continuation of examination, this examiner examined claim 1 according to the species SEQ ID No 52.
Drawings
Figure 3 of the instant application is an exact replicate of Makaryan’s Figure 1 (Makaryan et al., Curr Opin Hematol 22: 3-11 (2015)). Therefore, Figure 3 should be designated by a legend such as --Prior Art-- because only that which is old is illustrated. See MPEP § 608.02(g). Corrected drawings in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. The replacement sheet(s) should be labeled “Replacement Sheet” in the page header (as per 37 CFR 1.84(c)) so as not to obstruct any portion of the drawing figures. If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
The specifications is objected to for the following reasons:
Table 1, as identified in paragraph [0261] is not labeled Table 1. Please include a label. Appropriate correction is required.
The specifications contains conflicting language: “fold change” and “log2 fold change.” Figure 26B, paragraph [0101], which describes Figure 26B, and Table 1 (identified in paragraph [0261] use the language “log2 fold change” to describe promyelocyte to neutrophil enrichment scores. However, paragraphs [0262] and [0263] and the instant Claim 1 use the language “fold change” to describe the same scores. The data presented is consistent with the language “log2 fold change”. Appropriate correction is required.
Claim Objections
Claim 1 is objected to because of the following informalities: Claim 1 currently reads “wherein the synthetic nucleic acid is a guide RNA (gRNA) that promotes a promyelocyte to neutrophil enrichment fold change that is less than -0.1 when co-expressed in a cell with a DNA-targeting endonuclease Cas (CRISPR-associated) protein in a ribonucleoprotein (RNP) complex” The specifications contains conflicting language, “fold change” and “log2 fold change” to describe promyelocyte to neutrophil enrichment scores. Figure 26B, paragraph [0101], which describes Figure 26B, and Table 1 (identified in paragraph [0261] use the language “log2 fold change.” However, paragraphs [0262] and [0263] and the instant Claim 1 use the language “fold change.” The data presented is consistent with the language “log2 fold change,” and therefore, the claim should read, “wherein the synthetic nucleic acid is a guide RNA (gRNA) that promotes a promyelocyte to neutrophil enrichment log2 fold change (L2FC) that is less than -0.1 when co-expressed in a cell with a DNA-targeting endonuclease Cas (CRISPR-associated) protein in a ribonucleoprotein (RNP) complex…” Appropriate correction is required.
Claim 40 is objected to because of the following informalities: Claim 40 is incorrectly labeled as "Original." Claim 40 should be labeled "Withdrawn" consistent with Remarks in amendment made Nov 13, 2025. Claim 40 is not being examined on the merits. Appropriate correction is required.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim Interpretation
The crux of the instant application and Claim 1 is the use of CRISPR/Cas gene editing technologies for the treatment of severe congenital neutropenia (SCN) and other diseases caused by ELANE gene mutations. As evidence, this examiner points to the background section of the specification of the instant application, “Genome editing … is a promising strategy to enable cure of a variety of ELANE-associated diseases including… blood disorders like [cyclic neutropenia] CN and SCN.,” and “Provided here is an improved method of genome editing of the ELANE gene… The improved method comprises conditions for Cas9:sgRNA ribonucleoprotein (RNP)…”[0008]. Additionally, in the applicant’s traversal to rejection, they emphasize and make clear the point, by highlighting their strategy and findings by focusing on targeting the ELANE gene, aberrant neutrophil elastase (NE) expression, and neutrophil maturation/arrest (instant application specification [0088]-[0091], [0099], [0101], [0104], [0107]-[0112]; FIG. 12, FIG. 14, FIG. 23, FIG. 25B, FIG. 28A-28E, FIG. 34 as cited in traversal to rejection dated 2021 May 27).
The importance of aberrant NE expression and neutrophil arrest in the context of ELANE gene therapy, is that ELANE gene mutations lead to the aforementioned NE protein-truncation variants (PTVs). Early PTVs (ePTVs) follow Nagy’s “the 55-nt rule” and trigger the nonsense mediated decay (NMD) pathway. “The 55 nt rule” states, “only those termination codons located more than 50–55 nucleotides upstream of the 3’-most exon–exon junction (measured after splicing) mediate a reduction in mRNA abundance.” (page 198, column 2, line 7) (Nagy et al. A rule for termination-codon position within intron-containing genes: when nonsense affects RNA abundance. Trends Biochem Sci. 1998 Jun;23(6):198-9.). However, late PTVs (lPTVs) that do not observe “the 55-nt rule” escape the NMD pathway and lead to disease as recited by Kurosaki, “NMD surveys newly synthesized mRNAs and degrades those that harbor a premature termination codon (PTC), thereby preventing the production of truncated proteins that could result in disease in humans.” (Abstract) (Kurosaki et al. Nonsense-mediated mRNA decay in humans at a glance. J Cell Sci. 2016 Feb 1;129(3):461-7.). NE lPTVs follow this latter pattern, leading to neutrophil apoptosis and subsequently SCN. This is known in the prior art as recited by Dale, “Mutations in ELA2 result in the misfolding of neutrophil elastase, leading to … induction of apoptosis” (Page 3, column 3) (Dale et al. The many causes of severe congenital neutropenia. N Engl J Med. 2009 Jan 1;360(1):3-5.). Furthermore, it is known in the prior art that ELA2 mutations lead to PTV and eventually SCN as stated by Murakami, “… mutations that lead to splicing defects (~10%) and premature stop codons (~10%) also have been observed. … ELA2 mutations are associated with SCN…” (Introduction, column 1, 1st paragraph) (Murakami et al. Mutations of the ELA2 gene found in patients with severe congenital neutropenia induce the unfolded protein response and cellular apoptosis. Blood. 2007 Dec 15;110(13):4179-87.).
This examiner is interpreting the claims herein this application within the context of the state of prior art cited above, the prior art cited below, and the “crux” of the application for a person having ordinary skill in the art whose field of endeavor is the “use of CRISPR/Cas gene editing technologies for the treatment of severe congenital neutropenia (SCN) and other diseases caused by ELANE gene mutations.”
Claims 1-4, 6, 12, 20, and 27 are rejected under 35 U.S.C. 103 as being unpatentable over Nasri (Nasri et al., Blood (2017) 130 (Suppl_ 1 ): 542) in view of Makaryan (Makaryan et al., Curr Opin Hematol 22: 3-11 (2015)), Nagy (Nagy et al. Trends Biochem Sci. 1998 Jun;23(6):198-9.), Kurosaki (Kurosaki et al. J Cell Sci. 2016 Feb 1;129(3):461-7.), Takahashi (Takahashi et al., J Biol Chem 263:14739-47 (1988)), Dale (Dale et al. N Engl J Med. 2009 Jan 1;360(1):3-5.), Murakami (Murakami et al. Blood. 2007 Dec 15;110(13):4179-87.), Mali (Mali P,Science. 2013 Feb 15;339(6121):823-6. doi: 10.1126/science.1232033.), Lande (US 20190275104 A1; IDS ref.), and Hendel (Hendel et al., Nat Biotechnol 33: 985-89 (2015)).
Regarding claim 1, Nasri teaches a CRISPR ELANE gene editing platform to safely correct ELANE mutations in cells of patients to generate autologous cells for use in cell transplant therapies to treat congenital neutropenia (pg. 2, para. 2-4). The platform uses ribonucleoproteins (RNPs) made of Cas9 protein and a nucleic acid (Crispr-RNA) targeting a specific ELANE mutation in the genome for correction to provide autologous cells with fully restored granulocytic differentiation function (id.).
Therefore, Nasri teaches “A… nucleic acid …, wherein the… nucleic acid is a guide RNA (gRNA)… when co-expressed in a cell with a DNA-targeting endonuclease Cas (CRISPR-associated) protein in a ribonucleoprotein (RNP) complex…”
Nasri does not teach the nucleic acid expressly has at least one chemical modification (i.e., is synthetic), or wherein the nucleic acid comprises instant SEQ ID NO 52.
However Makaryan teaches severe congenital neutropenia (SCN) patients having mutations in exon 2 of the ELANE gene, e.g., C71, S67, or M66 missense mutations (Fig. 1). Furthermore, Takahashi teaches the ELANE gene, including its introns and exons in their mature form (Fig. 3). Included in Figure 3, exon 2 is noted. Exon 2 comprises instant SEQ ID NO 52. SEQ ID No 52 is 20 nt and matches bases 14- 33 of the ELANE gene’s mature exon 2. The region spanned by SEQ ID No 52 encodes for NE amino acids RRARPHA at amino acid position 5-11 of exon 2 of the mature NE protein. Furthermore, the ELANE gene contains, immediately adjacent downstream of its shared sequence encoding SEQ ID No 52, the nucleotide sequence TGG; a potential protospacer adjacent motive (PAM) site having the canonical NGG format. The PAM sequence is significant as recited by Mali in discussing both the location and length constraints of CRISPR/Cas9 systems and gRNAs, “… the requirement for the PAM (protospacer-adjacent motif) sequence -NGG following the 20–base pair (bp) crRNA target…” (page 823, column 2, 2nd paragraph) (Mali P, Yang L, Esvelt KM, Aach J, Guell M, DiCarlo JE, Norville JE, Church GM. RNA-guided human genome engineering via Cas9. Science. 2013 Feb 15;339(6121):823-6. doi: 10.1126/science.1232033.). Therefore, SEQ ID No 52 is a gRNA, having all the requisite hallmarks: it targets a gene of interest; it is 20 nt long; and it is directly upstream of a PAM site. An annotated excerpt of Takahasi’s Figure 3 is shown below. Annotated Figure 3 shows the ELANE gene region encompassing the sequence shared with SEQ ID No 52 and the PAM sequence required for CRISPR/Cas9 activation. The annotated figure also notes both the SEQ ID No 52 and PAM sequences.
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Therefore, Takahashi in light of Makaryan and Mali teaches the region of the ELANE gene identical to ‘’… a nucleic acid sequence selected from SEQ ID NOS: … 52...”
Lande teaches methods of using CRISPR gRNAs (consistent with the teachings of Mali) for targeted gene editing using a CRISPR RNA ("crRNA") and trans-activating crRNA ("tracrRNA"), as is the case with Cas9 ([0266]). Lande teaches synthesizing single guide RNAs (sgRNAs) comprising crRNA and tracrRNA sequences which are chemically modified ([0267]) and/or containing nucleoside analogs ([0278]) to confer advantages of higher specificity, improved on-target: off-target ratios, and increased stability ([0267]; [0383]; and as incorporated from teachings in Hendel (at Fig. 1 e-g; pg. 987, left col., 4th para. and right col., last two para.)).
Therefore, Lande, with the incorporated teachings of Hendel, teaches “A modified synthetic nucleic acid… wherein there is at least one chemical modification of a nucleotide in the synthetic nucleic acid.”
Nasri does not teach “wherein the synthetic nucleic acid… promotes a promyelocyte to neutrophil enrichment [log 2] fold change that is less than -0.1.”
However, having improved upon Nasri’s ELANE gene editing platform, and refined the performance and location of the gRNA, it would be obvious at the time of filing for a PHOSITA to determine the gRNA “… promotes a promyelocyte to neutrophil enrichment [log2] fold change that is less than -0.1” because the combined teachings of Dale, Murakami, Nagy, and Kurosaki and the motivation to treat ELANE mutation-based disease would have led a PHOSITA this this determination.
As recited above, the ELA2 mutation-based mechanism of SCN is known (ELA2 mutations lead to PTVs; PTVs lead to neutrophil apoptosis; neutrophil apoptosis leads to SCN) (Dale and Murakami). Similarly, it is known that lPTVs escape NMD whereas ePTVs succumb to NMD (Nagy). Furthermore, it is known that lPTVs lead to disease phenotypes whereas ePTVs do not lead to disease (Kurosaki). A PHOSITA would reasonably predict that targeting the early exon 2 of ELA2 would promote NMD whereas targeting later exons would lead to NMD escape and SCN. Furthermore, upon targeting the NE early exon 2 (prompting NMD, avoiding neutrophil apoptosis and SCN), they would also reasonably predict a promyelocyte to neutrophil enrichment of log2 fold change less than -0.1.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to improve Nasri’s CRISPR ELANE gene editing platform. It would have been obvious to do so by making and using a guide RNA comprising SEQ ID NO 52. It would have been obvious to have tried to make and use a guide RNA comprising SEQ ID NO 52. It would have been further obvious to optimize the SEQ ID No 52 gRNA by modifying it. It would have been obvious that upon editing the ELANE gene with modified gRNA SEQ ID No 52 within an early exon, exon 2, the gRNA would promote a promyelocyte to neutrophil enrichment log2 fold change that is less than -0.1.” It would have been obvious to a PHOSITA to do all of the aforementioned in combination to arrive at the instant invention of Claim 1 because this amounts to combining prior art elements according to known methods to yield predictable results.
At the time of filing of the invention, ELANE based disease was a recognized problem by a PHOSITA (as discussed above), specifically SCN. Nasri, Makaryan, Takahashi, Dale and Murakami each recognized the problem ELANE based diseased caused. Makaryan in particular, recognized mutations were a source of these problems and Dale and Murakami detailed the mechanism leading to SCN. Furthermore, Nasri recognized CRISPR/Cas9 was an effective strategy. Likewise, Lande and Hendel recognized CRISPR/Cas9, and specifically CRISPR systems with synthetically modified gRNAs were potent solutions to gene mutation problems.
A PHOSITA in this field of endeavor would search for a solution to SCN’s mutation-based mechanism. In their search, a PHOSITA would have known of NMD escape and Nagy’s “the 55-nt rule” and selected a target site more than 55 nt upstream of the 3’ most exon-exon junction, allowing the transcript to be subject to NMD. Furthermore, a PHOSITA would know CRISPR/Cas9’s limitations set by gRNA requirements, including sequence match, 20 nt length, and PAM location taught by Mali. Therefore, a PHOSITA would necessarily have been limited to a finite number regions within the ELANE gene to find predictable solutions. The region of ELANE sequence matching SEQ ID No 52 fits each of these parameters. Therefore, a PHOSITA would have known to target their gRNA to the region of ELANE matching SEQ ID No 52.
Regarding claims 2-4, Lande teaches methods of using CRISPR sgRNAs for targeting wherein the RNA comprises or mimics a crRNA and is chemically modified ([0267]) and/or contains nucleoside analogs ([0278]). Lande further teaches synthesizing sgRNAs for genome editing using 2'-O-thionocarbamate-protected nucleoside phosphoramidites, and 2'-O-methyl (M), 2'-O-methyl 3'phosphorothioate (MS) or 2'-O-methyl 3'thioPACE (MSP) incorporated at three terminal nucleotides at both the 5' and 3' ends ([0267]; [0383]) as incorporated from teachings in Hendel (at pg. 985, right col., 2nd para.).
it would have been obvious to substitute the gene editing platform’s gRNA of the combined teachings of Nasri, Makaryan, Nagy, Kurosaki, Takahashi, Lande, and Hendel as recited earlier, and substitute a terminal nucleotide, with a chemically modified with 2'-O-methyl (M), 2'-O-methyl 3'phosphorothioate (MS) of Lande as taught by Hendel and had a reasonable expectation of success because this simply amounts to simple substitution of one known element for another to obtain predictable results. A PHOSITA would have been familiar with the teachings of Lande and Hendel and known the chemical modification would yielded higher specificity, improved on-target: off-target ratios, and increased stability.
Therefore, Nasri, Makaryan, anagy, Kurosaki, Takahashi, Lande and Hendel teach claim 2 “…wherein the at least one chemical modifications is located at one or more terminal nucleotides in the synthetic nucleic acid.”
Similarly therefore, Nasri, Makaryan, Nagy, Kurosaki, Takahashi, Lande and Hendel teach the elected species 2'-O-methyl 3'phosphorothioate (MS) of claim 3 “… wherein the at least one chemical modification is selected from the group consisting of 2'-O-methyl 3'phosphorothioate (MS)...”
Similarly therefore, Nasri, Makaryan, anagy, Kurosaki, Takahashi, Lande and Hendel teach two of the embodiments of claim 4 “wherein the at least one chemical modification is … added at both the 5' and 3' ends of the synthetic nucleic acid” and “ or wherein the at least one chemical modification is located at first three nucleotides and at the last three nucleotides of the synthetic nucleic acid”, and therefore teach claim 4 “… wherein the at least one chemical modification is located only at the 3' end, or added only at the 5' end, or added at both the 5' and 3' ends of the synthetic nucleic acid; or wherein the at least one chemical modification is located at first three nucleotides and at the last three nucleotides of the synthetic nucleic acid.”
Regarding claim 6, as recited earlier, Nasri teaches the RNPs made of Cas9 protein and a CRISPR-RNA wherein the RNA is a crRNA nucleic acid targeting a specific ELANE mutation in the genome for correction (pg. 2, 2nd para.), and Lande teaches methods of targeting gene editing using chemically modified synthetic CRISPR sgRNAs comprising crRNA and tracrRNA sequences ([0266]).
It would have been obvious to substitute the gene editing platform’s chemically modified gRNA of the combined teachings of Nasri, Makaryan, Nagy, Kurosaki, Takahashi, Lande, and Hendel as recited earlier, and substitute either a crRNA sequence and/or a tracrRNA sequence as taught by the combination of Nasri, Lande, and Hendel and had a reasonable expectation of success because this simply amounts to simple substitution of one known element for another to obtain predictable results. A PHOSITA would have been familiar with the teachings of Nasri’s CRISPR RNA and the improved performance of Lande’s (and Hendel’s) modified synthetic crRNAs and tracrRNAs and subsequently would have expected higher specificity, improved on-target: off-target ratios, and increased stability with the modified crRNA or tracrRNA versus a generic gRNA alone.
Therefore, Nasri, Makaryan, anagy, Kurosaki, Takahashi, Lande and Hendel teach claim 6 “… wherein the modified synthetic nucleic acid sequence further comprises a crRNA sequence and/or tracrRNA sequence.”
Regarding claim 12, Lande teaches using the synthetic sgRNA in combination with a DNA-targeting endonuclease Cas (CRISPR-associated) protein (clustered regulatory interspaced short palindromic repeat (CRISPR) system) in an RNP complex, such as a Cas9 RNP complex taught by both Nasri (pg. 2, para. 2-4) and Lande ([0266][0267]).
It would have been obvious to substitute the “DNA-targeting endonuclease Cas (CRISPR-associated) protein” of the combined teachings of Nasri, Makaryan, Nagy, Kurosaki, Takahashi, Lande, and Hendel as recited earlier, and substitute a Cas9 protein as taught by both Nasri and Lande and had a reasonable expectation of success because this simply amounts to simple substitution of one known element for another to obtain predictable results because a PHOSITA would know Cas9 protein has the same function and structure as a DNA-targeting endonuclease and would therefore be interchangeable.
Therefore, Nasri, Makaryan, anagy, Kurosaki, Takahashi, Lande and Hendel teach claim 12 “… wherein the Cas protein is Cas 9.”
Regarding claims 20 and 27, Lande further teaches compositions comprising the synthetic sgRNA and a CRISPR nuclease ([0266]; [0271 ]), such as for altering a gene sequence in a cell ([0348]; [0002]; [0191]).
Although Lande does not expressly teach an RNP complex comprising a CRISPR endonuclease wherein the gRNA has at least one chemical modification and specifically comprises instant SEQ ID NO. 52, it would have been obvious to one of ordinary skill in the art before the effective time of filing to prepare an RNP complex of the Cas protein and the modified synthetic nucleic acid (sgRNA) comprising crRNA and tracrRNA sequences as taught by Lande and comprising instant SEQ ID NO. 52 as taught by Takahashi to align at exon 2 of the ELANE gene and wherein there is at least one chemical modification to a nucleotide in the sgRNA relative to common natural RNA molecules for improved stability and specificity as taught by Lande and Hendel. One of ordinary skill in the art with the goal of implementing a RNA-guided Cas9 system for editing a mutant codon of the ELANE gene as taught by Nasri, Makaryan, Takahashi, and Lande would need to form the RNP to carry out ELANE gene editing in a target cell, such as an autologous iPSC obtained from a SCN patient as taught by Nasri that encodes a mutation (e.g., C71 F, C71 R, C71 S, or C71 Y) as taught by Makaryan (Fig. 1 ) and further come to the conclusion that they would combine these elements into a composition.
Therefore, Nasri, Makaryan, anagy, Kurosaki, Takahashi, Lande and Hendel teach claim 20 “A composition comprising a modified synthetic nucleic acid of claim 1.”
Similarly, therefore, Nasri, Makaryan, anagy, Kurosaki, Takahashi, Lande and Hendel teach claim 27 “A ribonucleoprotein (RNP) complex comprising a DNA-targeting endonuclease Cas (CRISPR-associated) protein and a modified synthetic nucleic acid of claim 1.”
Response to Arguments
Applicant's arguments filed Nov. 13, 2025 have been fully considered but they are not persuasive.
Applicant traverses the previous obviousness rejections by arguing Makaryan teaches SCN patients have a mutation in exon 2 of the ELANE gene as well as the 5' UTR, exon 1-5, and introns III-IV of the ELANE gene, with the majority in exon 5, and thus there is no teaching or suggestion to focus specifically on exon 2. These arguments are not found to be persuasive for the same reasons as explained in the rejection dated May 16, 2025.
The applicant further traverses the obviousness rejections by adding detail to their argument, “The instant application teaches, for the first time, that targeting late exons of ELANE, in particular those at positions predicted to escape nonsense mediated decay (downstream from 55 nt upstream of final exon-exon boundary), tend to have positive promyelocyte-to-neutrophil enrichment scores, suggesting neutrophil maturation arrest. See, e.g., FIG. 26B.” This added detail does not improve the applicant’s argument, as noted in the rejection above. Furthermore, applicant's amendment necessitated the new ground(s) of indefinite and obviousness rejections presented above.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AARON DUREL WARD whose telephone number is (571)272-8495. The examiner can normally be reached Monday to Thursday 8:00AM 6:00PM.
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/AARON DUREL WARD/ Examiner, Art Unit 1636
/NEIL P HAMMELL/ Supervisory Patent Examiner, Art Unit 1636