Prosecution Insights
Last updated: April 18, 2026
Application No. 15/818,710

GUIDE RIBONUCLEIC ACID SEQUENCES THAT TARGET THE CCR5 GENE

Final Rejection §103§112
Filed
Nov 20, 2017
Examiner
WILSON, MICHAEL C
Art Unit
1638
Tech Center
1600 — Biotechnology & Organic Chemistry
Assignee
The Children's Hospital of Philadelphia
OA Round
10 (Final)
42%
Grant Probability
Moderate
11-12
OA Rounds
3y 9m
To Grant
59%
With Interview

Examiner Intelligence

Grants 42% of resolved cases
42%
Career Allow Rate
384 granted / 921 resolved
-18.3% vs TC avg
Strong +18% interview lift
Without
With
+17.7%
Interview Lift
resolved cases with interview
Typical timeline
3y 9m
Avg Prosecution
76 currently pending
Career history
997
Total Applications
across all art units

Statute-Specific Performance

§101
5.1%
-34.9% vs TC avg
§103
25.3%
-14.7% vs TC avg
§102
20.7%
-19.3% vs TC avg
§112
36.5%
-3.5% vs TC avg
Black line = Tech Center average estimate • Based on career data from 921 resolved cases

Office Action

§103 §112
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 arguments filed 3-28-25 have been fully considered but they are not persuasive. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action. Claims 2, 5, 14, 17-19 have been cancelled. Claims 20-24 have been added. Claims 1, 3, 4, 6-13, 15, 16, 20-24 are pending. Priority Claims 100 and 101 of provisional application 61/808594 filed 4-4-13 teach the concept of a guide RNA that targets the nucleic acid sequence of SEQ ID NO: 1-139 or a nucleic acid sequence that targets SEQ ID NO: 1-139 containing a single mismatch as required in claims 1, 14, 15. Therefore, the effective filing date of the claims is 4-4-13, the filing date of 61/808594. Claim objections Claim 1 can be written more clearly as ---A composition comprising isolated primary human CD34+ hematopoietic cells comprising two different guide ribonucleic acids (gRNAs) that target two different nucleotide sequences of a human C-C chemokine receptor type 5 (CCR5) gene, wherein the two different gRNAs are selected from the nucleic acid sequences of SEQ ID NO: 1-139---. 3. The composition of claim 1, wherein the gRNAs are modified. 4. The composition of claim 3, wherein the gRNAs are modified with pseudouridine… … or 5-azauridine-5’-triphosphate. Claim Interpretation Claims 1, 15, 22 require using two gRNAs that target the human CCR5 gene “and comprise sequences which are complementary and offset sequences selected from the group consisting of SEQ ID NOs: 1-139”. The claims do not require the gRNAs are different. The claims do not re quire the gRNAs target “offset” sequences that are different. The term “offset” does not make sense in the claims; the term may apply to two different target sequences in the CCR5 gene, but it does not apply the gRNAs because they exist independently of the CCR5 gene target sequences. Even if applicants were to use the term “offset” in context of the CCR5 gene, the term would be indefinite because it is unclear when two different target sequences are “offset”. Accordingly, the claims encompass the two gRNAs being the same or different. The claims are not limited to using two gRNAs that are different from each other or that target different areas of the human CCR5 gene. Claim Rejections - 35 USC § 112 Written Description Claims 1, 3, 4, 6-13, 15, 16 remain and claims 20-24 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 phrase “wherein each gRNA targets a nucleic acid sequence in a human CCR5 gene and comprise sequences which are complementary to offset sequences selected from the group consisting of SEQ ID NO: 1-139” in claim 1 lacks written description other than gRNA consisting of a nucleic acid sequence that is complementary to the nucleic acid sequence of SEQ ID NO: 1, 2, 3… .or 139. The phrase encompasses gRNA of any length comprising the nucleic acid of SEQ ID NO: 1, 2, 3… …or 139. However, the specification does not teach any gRNAs other than those consisting of SEQ ID NOs: 1-139. This issue also applies to independent claims 15, 22. Response to arguments Applicants argue the amendment overcomes the rejection. Applicants’ argument is not persuasive. The amendment does not address the issue at hand. Indefiniteness 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, 3, 4, 6-13, 15, 16, 20-24 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. The phrase “wherein each gRNA targets a nucleic acid sequence in a human CCR5 gene and comprise sequences which are complementary to offset sequences selected from the group consisting of SEQ ID NO: 1-139” in claim 1, 15, 22 makes the claims indefinite. The term “offset” does not make sense in the claims. While two different target sequences in the CCR5 gene may be “offset”, the term does not apply the gRNAs because they exist independently of the CCR5 gene target sequences. Even if applicants were to use the term “offset” in context of two different target sequences of the CCR5 gene, the term would still be indefinite because it is unclear when two different target sequences are “offset”. For example, it is unclear whether the sequences must be mutually exclusive or if overlapping is allowed. Or perhaps overlapping is essential and defines when target sequences are “offset”. It is also unclear whether a target sequence that contains another target sequence that is shorter is considered “offset”. The specification and the art provide no definition that is helpful in determining the metes and bounds of the claim. Therefore, those of skill would not be able to determine when they were infringing on the claim. Claim Rejections - 35 USC § 103 A) Claims 1, 3, 7-13, 15, 16 remain and claims 20-22, 24 are rejected under 35 USC 103 as being unpatentable over Masquelier (AIDS, 2007, Vol. 21, No. 1, pg 111-113), Mali (Science, Feb. 2013, published online 1-3-13, Vol. 339, pg 823-826), Cong (Science, Feb. 2013, published online 1-3-13, Vol. 339, pg 819-8823), and Ando (7951925). The following rejection uses two-way obviousness with either Masquelier or Mali as the primary reference. The effective filing date of SEQ ID NO: 1 is 4-4-13, the filing date of Priority document 61808594. Masquelier described the human CCR5 gene AY947540 which contains SEQ ID NO: 1 and 2 as required in claims 1, 15 and 22. SEQ ID NO: 1 PNG media_image1.png 854 447 media_image1.png Greyscale SEQ ID NO: 2 PNG media_image2.png 856 453 media_image2.png Greyscale Masquelier did not teach gRNAs that target and are complementary to SEQ ID NO: 1 and 2 as required in claims 1, 15 and 22. However, human cells containing one or two gRNAs that target and inactivate genes were well-known in the art as described by Mali (pg 824, col. 2, 293T, K562, and iPS cells; T1 and T2 in Fig. 1). Claims 1, 15 and 22 require using two gRNAs that target the human CCR5 gene and encompass the two gRNAs being the same or different; they are not limited to using two gRNAs that are different from each other or that target different areas of the human CCR5 gene. Thus it would have been obvious to those of ordinary skill in the art at the time of filing to identify two target sequences in a gene of interest, make one or two gRNAs that bind those target sequences, and put those one or two gRNAs into an isolated human cell using the teachings of Mali, particularly via the http://CRISPR.mit.edu website wherein the gene of interest was the mutant human CCR5 gene described by Masquelier which contains SEQ ID NO: 1 and/or 2. Those of ordinary skill in the art at the time of filing would have been motivated to make one or two gRNAs that target the CCR5 gene to inactivate the human CCR5 gene. Applicants acknowledge it was well known to use the website to identify gRNA target sites and design gRNAs on pg 32, para 108. It was also well known how to identify gRNA target sites and design gRNAs using the teachings of Mali and the art at the time of filing. In a reverse interpretation, Mali taught isolated human cells with one or two gRNAs that target and inactivate a gene (pg 824, col. 2, 293T, K562, and iPS cells; T1 and T2 in Fig. 1) but did not teach the gene was CCR5. However, Masquelier described the human CCR5 gene AY947540 which contains SEQ ID NO: 1 and 2 as required in claims 1, 7, 15, 18, 22. Thus, it would have been obvious to those of ordinary skill in the art at the time of filing to target one or two sequences in one gene using gRNA as described by Mali using the CCR5 gene sequence described by Masquelier. Those of ordinary skill in the art at the time of filing would have been motivated to specifically target the AY947540 sequence of Masquelier to correct the mutation of the CCR5 gene, to knockout the CCR5 gene, or to recapitulate the novel 24-base pair deletion in the coding region of CCR5 that infers complete resistance of individuals to macrophage-tropic HIV-1 infection. Those of ordinary skill would have had a reasonable expectation of success in identifying gRNA targets for the CCR5 gene because Cong and Mali taught how to identify gRNA target sequences and make gRNA. The website http://CRISPR.mit.edu for designing gRNA was available to the public at the time of filing. Applicants acknowledge it was well known to use the website to identify gRNA target sites and design gRNAs on pg 32, para 108. It was also well known how to identify gRNA target sites and design gRNAs using the teachings of Mali and the art at the time of filing. The combined teachings of Masquelier, Mali and Cong did not teach the cells were primary CD34+ hematopoietic stem cells as required in claims 1, 15 and 22. However, Ando taught isolated human primary CD34+ hematopoietic stem cells comprising a pair of endonucleases that modify an endogenous CCR5 gene (col. 25, Example 4; claim 14, 16, 19). Thus it would have been obvious to those of ordinary skill in the art at the time of filing to make an isolated human cell comprising one or two gRNAs complementary or identical to SEQ ID NO: 1-139 as described by the combined teachings of Masquelier and Mali wherein the cells were isolated human primary CD34+ hematopoietic cells described by Ando. Those of ordinary skill in the art at the time of filing would have been motivated to replace the cells of Mali with the hematopoietic cells of Ando to obtain hematopoietic cells with a knockout of CCR5 for HIV resistance (col. 1, lines 53-55 of Ando). Ando provides evidence that targeting two different sites on a CCR5 gene using an endonuclease to obtain a desired modification in primary human hematopoietic cells was well-known. Ando provides motivation to use a 2-target site approach to modify the CCR5 gene in primary human hematopoietic cells using an endonuclease. Mali modified the nucleotides of the gRNAs by processing pre-crRNA and tracrRNA together (pg 823, col. 2). Therefore, each of the nucleotides are inherently “modified” during the process as required in claim 3. A nucleic acid sequence that targets SEQ ID NO: 1 was obvious for reasons set forth above as required in claim 7. Mali used gRNAs in combination with a nucleic acid sequence encoding a codon-optimized Cas9 operably linked to a CMV promoter (Fig. 1B) as required in claims 8-11. Mali taught using a nucleic acid sequence encoding GFP as a “repair donor” (Fig. 1B) as required in claim 12. Mali incorporated gRNA into the pCR-BluntII-TOPO vector (Invitrogen) (pg 7 of supplemental materials) which is a plasmid as required in claim 13. Mali used Cas9 (Fig. 1B) which is a Cas protein as required in claim 16. Claims 20-22, 24 have been included for reasons set forth above. Response to arguments Applicants argue the Examiner’s interpretation of Ando is erroneous because Ando cannot establish targeting two different sites on a CCR5 gene using a single endonuclease. Applicants’ argument is not persuasive. Ando establishes it was well-known to identify two different target sites on a CCR5 gene for use with a pair of ZFNs. Applicants argue the office has not met its burden for obviousness (pg 9-10). Applicants’ argument is not persuasive. All of the limitations are discussed in the rejection. A motivational statement has been provided. The rejection is sound. Applicants argue the rejection does not provide a convincing line of reasoning. Applicants’ argument is not persuasive. All of the limitations are discussed in the rejection. A motivational statement has been provided. The rejection is sound. Applicants argue the office has improperly relied upon the CRISPR.mit.edu website in the rejection. Applicants’ argument is not persuasive. The website is not one of the references cited in the rejection. The Examiner simply points out that applicants acknowledged it was well known to use the website to identify gRNA target sites and design gRNAs on pg 32, para 108. The Examiner also points out it was also well known how to identify gRNA target sites and design gRNAs using the teachings of Mali and the art at the time of filing. Therefore, those of skill had a reasonable expectation of success in applying CRISPR technology to the CCR5 gene. Applicants argue the office discounted the unpredictability of the “efficiency” of modifying “primary” cells using CRISPR technology and point to Hendel. Applicants’ argument is not persuasive. The claims merely require putting gRNAs in primary cells; they do not require any amount of “efficiency” or making any predictable genetic modification. A proper “unexpected results” argument must begin with what was expected and compare it to applicants’ results. Fig. 5B, 6B, and 7 do not compare the two-gRNA approach in 293T, K562, or iPS cells described by Mali to a two-gRNA approach in human hematopoietic cells. Any “optimization” or efficiency between cell-types bears no weight in the obviousness analysis. Any degree of efficiency is sufficient for the claimed invention. The claims do not require obtaining “increased” efficiency of modification as compared to the teachings of Mali or Cong. It remains unfathomable how Fig. 5B shows what was expected or unexpected. B) Claims 1, 3, 6-13, 15, 16 remain and claims 20-22, 24 are rejected under 35 USC 103 as being unpatentable over Kim (WO 2010143917), Mali (Science, Feb. 2013, Vol. 339, pg 823-826), Cong (Science, Feb. 2013, Vol. 339, pg 819-8823) and Ando (7951925). The effective filing date of SEQ ID NO: 28 is 4-4-13, the filing date of Priority document 61808594. Kim described the human CCR5 gene which contains SEQ ID NO: 27 and 28 as required in claims 1, 6, 7, 15, 22. SEQ ID NO: 27 PNG media_image3.png 742 403 media_image3.png Greyscale SEQ ID NO: 28 PNG media_image4.png 822 442 media_image4.png Greyscale Kim did not teach gRNAs consisting of SEQ ID NO: 27 and 28 as required in claims 1, 6, 7, 15, 22. However, human cells with one or two gRNAs that target and inactivate genes were well-known in the art as described by Mali (pg 824, col. 2, 293T, K562, and iPS cells; T1 and T2 in Fig. 1). Claims 1, 15, 22 require using two gRNAs that target the human CCR5 gene and encompass the two gRNAs being the same or different; they are not limited to using two gRNAs that are different from each other or that target different areas of the human CCR5 gene. Thus it would have been obvious to those of ordinary skill in the art at the time of filing to identify one or two target sequences in a gene of interest, make one or two gRNA that bind those target sequences, and put those one or two gRNAs into an isolated human cell using the teachings of Mali, particularly via the http://CRISPR.mit.edu website wherein the gene of interest was the mutant human CCR5 gene described by Kim which contains SEQ ID NO: 27 and 28. Those of ordinary skill in the art at the time of filing would have been motivated to make one or two gRNAs that target the CCR5 gene to inactivate the human CCR5 gene. Those of ordinary skill in the art at the time of filing would have been motivated to specifically target the AYM92132 sequence of Kim to inactivate the CCR5 gene. Applicants acknowledge it was well known to use the website to identify gRNA target sites and design gRNAs on pg 32, para 108. It was also well known how to identify gRNA target sites and design gRNAs using the teachings of Mali and the art at the time of filing. In a reverse interpretation, Mali taught isolated human cells with one or two gRNAs that target and inactivate a gene (pg 824, col. 2, 293T, K562, and iPS cells; T1 and T2 in Fig. 1) but did not teach the gene was CCR5. However, Kim described SEQ ID NO: 27 and 28 as required in claims 1, 6, 7, 15, 22. Thus, it would have been obvious to those of ordinary skill in the art at the time of filing to target one or two sequences in one gene using gRNA as described by Mali using the CCR5 gene sequence described by Kim. Those of ordinary skill in the art at the time of filing would have been motivated to specifically target the AYM92132 sequence of Kim to inactivate the CCR5 gene. Those of ordinary skill would have had a reasonable expectation of success in identifying gRNA targets for the CCR5 gene because Cong and Mali taught how to identify gRNA target sequences and make gRNA. The website http://CRISPR.mit.edu for designing gRNA was available to the public at the time of filing. Applicants acknowledge the website was used by applicants to design the gRNA (pg 32, para 108). Applicants acknowledge it was well known to use the website to identify gRNA target sites and design gRNAs on pg 32, para 108. It was also well known how to identify gRNA target sites and design gRNAs using the teachings of Mali and the art at the time of filing. The combined teachings of Kim, Mali and Cong did not teach the cells were primary CD34+ hematopoietic stem cells as required in claims 1, 15, 22. However, Ando taught isolated human primary CD34+ hematopoietic stem cells comprising a pair of endonucleases that modify an endogenous CCR5 gene (col. 25, Example 4; claim 14, 16, 19). Thus it would have been obvious to those of ordinary skill in the art at the time of filing to make an isolated human cell comprising one or two gRNAs complementary or identical to SEQ ID NO: 1-139 as described by the combined teachings of Kim, Mali and Cong wherein the cells were isolated human primary CD34+ hematopoietic cells described by Ando. Those of ordinary skill in the art at the time of filing would have been motivated to replace the cells of Mali with the primary hematopoietic cells of Ando to obtain hematopoietic cells with a knockout of CCR5 for HIV resistance (col. 1, lines 53-55 of Ando). Ando provides evidence that targeting two different sites on a CCR5 gene using an endonuclease to obtain a desired modification in primary human hematopoietic cells was well-known. Ando provides motivation to use a 2-target site approach to modify the CCR5 gene in primary human hematopoietic cells using an endonuclease. Mali modified the nucleotides of the gRNAs by processing pre-crRNA and tracrRNA together (pg 823, col. 2). Therefore, each of the nucleotides are inherently “modified” during the process as required in claim 3. A nucleic acid sequence that targets SEQ ID NO: 28 was obvious for reasons set forth above as required in claim 6. A nucleic acid sequence that targets SEQ ID NO: 27 was obvious for reasons set forth above as required in claim 7. Mali used gRNAs in combination with a nucleic acid sequence encoding a codon-optimized Cas9 operably linked to a CMV promoter (Fig. 1B) as required in claims 8-11. Mali taught using a nucleic acid sequence encoding GFP as a “repair donor” (Fig. 1B) as required in claim 12. Mali incorporated gRNA into the pCR-BluntII-TOPO vector (Invitrogen) (pg 7 of supplemental materials) which is a plasmid as required in claim 13. Mali used Cas9 (Fig. 1B) which is a Cas protein as required in claim 16. Claims 20-22, 24 have been included for reasons cited above. Response to arguments Applicants argue the Examiner’s interpretation of Ando is erroneous because Ando cannot establish targeting two different sites on a CCR5 gene using a single endonuclease. Applicants’ argument is not persuasive. Ando establishes it was well-known to identify two different target sites on a CCR5 gene for use with a pair of ZFNs. Applicants argue the office has not met its burden for obviousness (pg 9-10). Applicants’ argument is not persuasive. All of the limitations are discussed in the rejection. A motivational statement has been provided. The rejection is sound. Applicants argue the rejection does not provide a convincing line of reasoning. Applicants’ argument is not persuasive. All of the limitations are discussed in the rejection. A motivational statement has been provided. The rejection is sound. Applicants argue the office has improperly relied upon the CRISPR.mit.edu website in the rejection. Applicants’ argument is not persuasive. The website is not one of the references cited in the rejection. The Examiner simply points out that applicants acknowledged it was well known to use the website to identify gRNA target sites and design gRNAs on pg 32, para 108. The Examiner also points out it was also well known how to identify gRNA target sites and design gRNAs using the teachings of Mali and the art at the time of filing. Therefore, those of skill had a reasonable expectation of success in applying CRISPR technology to the CCR5 gene. Applicants argue the office discounted the unpredictability of the “efficiency” of modifying “primary” cells using CRISPR technology and point to Hendel. Applicants’ argument is not persuasive. The claims merely require putting gRNAs in primary cells; they do not require any amount of “efficiency” or making any predictable genetic modification. A proper “unexpected results” argument must begin with what was expected and compare it to applicants’ results. Fig. 5B, 6B, and 7 do not compare the two-gRNA approach in 293T, K562, or iPS cells described by Mali to a two-gRNA approach in human hematopoietic cells. Any “optimization” or efficiency between cell-types bears no weight in the obviousness analysis. Any degree of efficiency is sufficient for the claimed invention. The claims do not require obtaining “increased” efficiency of modification as compared to the teachings of Mali or Cong. It remains unfathomable how Fig. 5B shows what was expected or unexpected. C) Claim 4 remains and claim 23 is rejected under 35 USC 103 as being unpatentable over Masquelier (AIDS, 2007, Vol. 21, No. 1, pg 111-113), Mali (Science, Feb. 2013, published online 1-3-13, Vol. 339, pg 823-826), Cong (Science, Feb. 2013, published online 1-3-13, Vol. 339, pg 819-8823), and Ando (7951925) as applied to claims 1, 3, 7-13, 15, 16, 20-22, 24 and further in view of Joung (9885033). The combined teachings of Masquelier, Mali, Cong, and Ando taught an isolated human CD34+ hematopoietic cell comprising two gRNAs that target SEQ ID NO: 1 and 2 in an endogenous CCR5 gene. The combined teachings of Masquelier, Mali, Cong, and Ando did not teach nucleotides of the gRNAs were modified using pseudouridine, 5-methylcytodine… as required in claim 4, 23. However, it was well-known to modify gRNA with pseudouridine or 5-methylcytodine as described by Joung (col. 2, lines 18-26). Provisional application 61/83818 of Joung supports the concept going back to June 21, 2013. Thus it would have been obvious to those of ordinary skill in the art at the time of filing to make isolated human CD34+ hematopoietic cell comprising two gRNAs that target SEQ ID NO: 1 and 2 in an endogenous CCR5 gene as described by the combined teachings of Masquelier, Mali, Cong, and Ando using modified gRNA as described by Joung. Those of ordinary skill in the art at the time of filing would have been motivated to modify the gRNAs to “increase specificity” (col. 17, “Synthetic alternatives to standard gRNAs to improve specificity”). Response to argument Applicants’ mention of this rejection, but the discussion does not rise to the level of an argument. D) Claim 4 remains and claim 23 is rejected under 35 USC 103 as being unpatentable over Kim (WO 2010143917), Mali (Science, Feb. 2013, published online 1-3-13, Vol. 339, pg 823-826), Cong (Science, Feb. 2013, published online 1-3-13, Vol. 339, pg 819-8823), and Ando (7951925) as applied to claims 1, 3, 7-13, 15, 16, 20-22, 24 and further in view of Joung (9885033). The combined teachings of Kim, Mali, Cong, and Ando taught an isolated human CD34+ hematopoietic cell comprising two gRNAs that target SEQ ID NO: 27 and 28 in an endogenous CCR5 gene. The combined teachings of Kim, Mali, Cong, and Ando did not teach nucleotides of the gRNAs were modified using pseudouridine, 5-methylcytodine… as required in claim 4, 23. However, it was well-known to modify gRNA with pseudouridine or 5-methylcytodine as described by Joung (col. 2, lines 18-26). Provisional application 61/83818 of Joung supports the concept going back to June 21, 2013. Thus it would have been obvious to those of ordinary skill in the art at the time of filing to make isolated human CD34+ hematopoietic cell comprising two gRNAs that target SEQ ID NO: 1 and 2 in an endogenous CCR5 gene as described by the combined teachings of Kim, Mali, Cong, and Ando using modified gRNA as described by Joung. Those of ordinary skill in the art at the time of filing would have been motivated to modify the gRNAs to “increase specificity” (col. 17, “Synthetic alternatives to standard gRNAs to improve specificity”). Response to argument Applicants’ mention of this rejection, but the discussion does not rise to the level of an argument. Conclusion The prior art made of record and not relied upon is considered pertinent to applicant's disclosure: Cradick, Nucleic Acids Res. 2013, Vol. 41, No. 20, pg 9584-9592. 2016/0143953 para 164 safe harbor locus, cd34+ cell with transgenes in safe harbor ccr5 made by ZFNs TALENs or CRISPR as in 7,951,925 and 8,110,379; U.S. Publication Nos. 20080159996; 201000218264; 20120017290; 20110265198; 20130137104; 20130122591; 20130177983 and 20130177960 and U.S. Provisional Application No. 61/823,689. Claim 5. Maier (Human Gene Therapy, March 2013, Vol. 24, pg 245-258) primary CD34+ cells with ZFNs that disrupt CCR5 gene. Holt (Nature Biotech, 2010, Vol. 28, No. 8, pg 839-847). Cho (Nature Biotech., March 2013, Vol. 31, No. 3, pg 230-232) and Supplemental materials: Fig. 3 shows SEQ ID NO: 1. No claim is allowed. Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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. Inquiry concerning this communication or earlier communications from the examiner should be directed to Michael C. Wilson who can normally be reached at the office on Monday through Friday from 9:30 am to 6:00 pm at 571-272-0738. Patent applicants with problems or questions regarding electronic images that can be viewed in the Patent Application Information Retrieval system (PAIR) can now contact the USPTO’s Patent Electronic Business Center (Patent EBC) for assistance. Representatives are available to answer your questions daily from 6 am to midnight (EST). The toll free number is (866) 217-9197. When calling please have your application serial or patent number, the type of document you are having an image problem with, the number of pages and the specific nature of the problem. The Patent Electronic Business Center will notify applicants of the resolution of the problem within 5-7 business days. Applicants can also check PAIR to confirm that the problem has been corrected. The USPTO’s Patent Electronic Business Center is a complete service center supporting all patent business on the Internet. The USPTO’s PAIR system provides Internet-based access to patent application status and history information. It also enables applicants to view the scanned images of their own application file folder(s) as well as general patent information available to the public. For all other customer support, please call the USPTO Call Center (UCC) at 800-786-9199. If attempts to reach the examiner are unsuccessful, the examiner's supervisor, Tracy Vivlemore, can be reached on 571-272-2914. The official fax number for this Group is (571) 273-8300. Michael C. Wilson /MICHAEL C WILSON/ Primary Examiner, Art Unit 1638
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Prosecution Timeline

Nov 20, 2017
Application Filed
Sep 04, 2018
Non-Final Rejection — §103, §112
Jan 14, 2019
Response Filed
Apr 16, 2019
Final Rejection — §103, §112
Oct 22, 2019
Notice of Allowance
May 22, 2020
Request for Continued Examination
May 27, 2020
Response after Non-Final Action
Jul 21, 2020
Non-Final Rejection — §103, §112
Jan 27, 2021
Response Filed
Apr 15, 2021
Final Rejection — §103, §112
Oct 20, 2021
Notice of Allowance
Mar 21, 2022
Request for Continued Examination
Mar 23, 2022
Response after Non-Final Action
Jun 03, 2022
Non-Final Rejection — §103, §112
Dec 07, 2022
Response Filed
Feb 14, 2023
Final Rejection — §103, §112
May 23, 2023
Request for Continued Examination
May 25, 2023
Response after Non-Final Action
Jul 28, 2023
Non-Final Rejection — §103, §112
Jan 03, 2024
Response Filed
Feb 29, 2024
Final Rejection — §103, §112
Sep 05, 2024
Request for Continued Examination
Sep 06, 2024
Response after Non-Final Action
Sep 27, 2024
Non-Final Rejection — §103, §112
Mar 28, 2025
Response Filed
Mar 31, 2025
Response after Non-Final Action
Dec 04, 2025
Final Rejection — §103, §112
Apr 09, 2026
Notice of Allowance

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Prosecution Projections

11-12
Expected OA Rounds
42%
Grant Probability
59%
With Interview (+17.7%)
3y 9m
Median Time to Grant
High
PTA Risk
Based on 921 resolved cases by this examiner. Grant probability derived from career allow rate.

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