ataDETAILED 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 .
Claims 1-20 are pending.
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-14, in the reply filed on 2-13-26 is acknowledged.
Claims 15-20 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 2-13-26.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
A) Claims 1-12 are rejected under 35 U.S.C. 103 as being unpatentable over Kerr (RU 2816871), Stanton (WO 2022226008), Riling (WO 2022165027), Esteves (20210381004), Stanton (WO 2021236479), Kerr (CA 3172572), and Kerr (20220119840) in view of Clark (Sci.,2003, Vol. 302, No. 5652, pg 1960-1963), Wang (WO 2018108106), Nagase (DNA Res., 2008, Vol. 15, No. 3, pg 137-149), J5390642 (2011), JS5390508 (2011), JS53090481 (2011), Mehra (WO 20220660911), Ciuffi (Nature Med., 2005, Vol. 11, No. 12, pg 1287-1289), and JS390642
Kerr (RU 2816871), Stanton (WO 2022226008), Riling (WO 2022165027), Esteves (20210381004), Stanton (WO 2021236479), Kerr (CA 3172572), and Kerr (20220119840) taught AAV vectors encoding a protein of interest operably linked to 5’ and 3’ ITRs, a CAG promoter, a WPRE, and a bGH polyA sequence (See Examples and Figures). See for example Esteves:
PNG
media_image1.png
152
414
media_image1.png
Greyscale
and
Kerr (WO 2020154645) taught:
PNG
media_image2.png
464
540
media_image2.png
Greyscale
Kerr (RU 2816871) taught the protein was INFβ (para 450).
Stanton (WO 2022226008) taught the protein was INFβ (pg 83, line 8):
PNG
media_image3.png
288
532
media_image3.png
Greyscale
Riling (WO 2022165027) taught the protein was INFβ:
PNG
media_image4.png
400
532
media_image4.png
Greyscale
Esteves (20210381004) taught the protein was INFβ (Table 2).
Stanton (WO 2021236479) taught the protein was INFβ:
PNG
media_image5.png
236
514
media_image5.png
Greyscale
Kerr (CA 3172572) taught the protein was INFβ (para 412)
Kerr (20220119840)
Kerr (RU 2816871), Stanton (WO 2022226008), Riling (WO 2022165027), Esteves (20210381004), Stanton (WO 2021236479), Kerr (CA 3172572), and Kerr (20220119840) did not teach the sequence encoding INFβ was at least 95% identical to SEQ ID NO: 4.
However, Clark (Sci.,2003, Vol. 302, No. 5652, pg 1960-1963) taught AY414516 which is 98.9% identical to SEQ ID NO: 4:
PNG
media_image6.png
860
394
media_image6.png
Greyscale
Clark (Sci., 2003, Vol. 302, No. 5652, pg 1960-1963) also taught AY414517 which is 96.9% identical to SEQ ID NO: 4:
PNG
media_image6.png
860
394
media_image6.png
Greyscale
Wang (WO 2018108106) taught BFK14568 which is 99.1% identical to SEQ ID NO: 4:
PNG
media_image7.png
848
434
media_image7.png
Greyscale
Nagase (DNA Res., 2008, Vol. 15, No. 3, pg 137-149) taught AB587428 which is 98.9% identical to SEQ ID NO: 4:
PNG
media_image8.png
646
394
media_image8.png
Greyscale
PNG
media_image9.png
436
372
media_image9.png
Greyscale
Thus, it would have been obvious to those of ordinary skill in the art at the time of filing to make an AAV vector comprising an ITR, a CAG promoter, a nucleic acid sequence encoding IFNβ, a WPRE, a bGH polyA, and a second ITR as described by Kerr (RU 2816871), Stanton (WO 2022226008), Riling (WO 2022165027), Esteves (20210381004), Stanton (WO 2021236479), Kerr (CA 3172572), and Kerr (20220119840) wherein the nucleic acid sequence encoding IFNβ operably linked to that is at least 95% identical to SEQ ID NO: 4 as described by Clark, Wang, and Nagase. Those of ordinary skill in the art at the time of filing would have been motivated to use the nucleic acid sequence encoding IFNβ described by Clark, Wang, and Nagase because they are functional equivalents and because they lack a stop codon. Those of skill would have wanted to swap coding sequences as a matter of design choice for optimization and for when the stop codon isn’t needed.
Kerr (RU 2816871), Stanton (WO 2022226008), Riling (WO 2022165027), Esteves (20210381004), Stanton (WO 2021236479), Kerr (CA 3172572), and Kerr (20220119840) did not teach ITRs that were SEQ ID NO: 40. However, ITR’s that are 100% identical to SEQ ID NO: 40 were well-known in the art:
PNG
media_image10.png
566
408
media_image10.png
Greyscale
PNG
media_image11.png
558
432
media_image11.png
Greyscale
PNG
media_image12.png
552
408
media_image12.png
Greyscale
Thus, it would have been obvious to those of ordinary skill in the art at the time of filing to make an AAV vector comprising an ITR, a CAG promoter, a nucleic acid sequence encoding IFNβ, a WPRE, a bGH polyA, and a second ITR as described by Kerr (RU 2816871), Stanton (WO 2022226008), Riling (WO 2022165027), Esteves (20210381004), Stanton (WO 2021236479), Kerr (CA 3172572), and Kerr (20220119840) wherein the ITRs were SEQ ID NO: 40 as described by J5390642, J5390508, J5390481. Those of ordinary skill in the art at the time of filing would have been motivated to use the ITRs described by J5390642, J5390508, J5390481because they are functional equivalents. Those of skill would have wanted to swap coding sequences as a matter of design choice for optimization.
Kerr (RU 2816871), Stanton (WO 2022226008), Riling (WO 2022165027), Esteves (20210381004), Stanton (WO 2021236479), Kerr (CA 3172572), and Kerr (20220119840) did not teach a CAG promoter that were at least 95% identical to SEQ ID NO: 40. However, CAG that is 97.7% identical to SEQ ID NO: 48 were described by Mehra (WO 20220660911):
PNG
media_image13.png
604
434
media_image13.png
Greyscale
PNG
media_image14.png
748
444
media_image14.png
Greyscale
Thus, it would have been obvious to those of ordinary skill in the art at the time of filing to make an AAV vector comprising an ITR, a CAG promoter, a nucleic acid sequence encoding IFNβ, a WPRE, a bGH polyA, and a second ITR as described by Kerr (RU 2816871), Stanton (WO 2022226008), Riling (WO 2022165027), Esteves (20210381004), Stanton (WO 2021236479), Kerr (CA 3172572), and Kerr (20220119840) wherein the CAG promoter was 97.7% identical to SEQ ID NO: 48 as described by Mehra (WO 20220660911). Those of ordinary skill in the art at the time of filing would have been motivated to use the CAG described by Mehra (WO 20220660911) because it is functional equivalent. Those of skill would have wanted to swap coding sequences as a matter of design choice for optimization.
Kerr (RU 2816871), Stanton (WO 2022226008), Riling (WO 2022165027), Esteves (20210381004), Stanton (WO 2021236479), Kerr (CA 3172572), and Kerr (20220119840) did not teach a WPRE that was at least 95% identical to SEQ ID NO: 33. However, a WPRE that is 98.1% identical to SEQ ID NO: 33 was taught by Cuiffe (DU644248, DU644244):
PNG
media_image15.png
854
376
media_image15.png
Greyscale
PNG
media_image16.png
846
368
media_image16.png
Greyscale
Thus, it would have been obvious to those of ordinary skill in the art at the time of filing to make an AAV vector comprising an ITR, a CAG promoter, a nucleic acid sequence encoding IFNβ, a WPRE, a bGH polyA, and a second ITR as described by Kerr (RU 2816871), Stanton (WO 2022226008), Riling (WO 2022165027), Esteves (20210381004), Stanton (WO 2021236479), Kerr (CA 3172572), and Kerr (20220119840) wherein the WPRE was at least 95% identical to SEQ ID NO: 33 as described by Ciuffi. Those of ordinary skill in the art at the time of filing would have been motivated to use the WPRE described by Ciuffi because it is functional equivalent. Those of skill would have wanted to swap coding sequences as a matter of design choice for optimization.
Kerr (RU 2816871), Stanton (WO 2022226008), Riling (WO 2022165027), Esteves (20210381004), Stanton (WO 2021236479), Kerr (CA 3172572), and Kerr (20220119840) did not teach a bGH polyA that was at least 95% identical to SEQ ID NO: 34. However, the bGH polyA of SEQ ID NO: 34 was well known as described by JS390642 (2011):
PNG
media_image17.png
596
444
media_image17.png
Greyscale
Thus, it would have been obvious to those of ordinary skill in the art at the time of filing to make an AAV vector comprising an ITR, a CAG promoter, a nucleic acid sequence encoding IFNβ, a WPRE, a bGH polyA, and a second ITR as described by Kerr (RU 2816871), Stanton (WO 2022226008), Riling (WO 2022165027), Esteves (20210381004), Stanton (WO 2021236479), Kerr (CA 3172572), and Kerr (20220119840) wherein the polyA was at least 95% identical to SEQ ID NO: 34 as described by JS390642. Those of ordinary skill in the art at the time of filing would have been motivated to use the polyA described by JS390642 because it is functional equivalent. Those of skill would have wanted to swap coding sequences as a matter of design choice for optimization.
The concept of a “sequence encoding a CpG-depleted human interferon β (IFNβ)” in claim 1, item c) has been included because the metes and bounds are unclear and because some sequences encoding the INFβ are less CpG’d than others.
Claim 2 has been included because:
SEQ ID NO: 40 was well-known as described by J5390642, J5390508, J5390481;
SEQ ID NO: 48 was well-known as described by Mehra;
SEQ ID NO: 4 is an obvious variant of the sequences described by Clark, Wang, and Nagase because there is only one indel and one mismatch which do not effectively change the structure or function of the coding sequence or the resultant IFNβ;
SEQ ID NO: 33 is an obvious variant of the WPRE that is 98.1% identical to SEQ ID NO: 33 taught by Cuiffe because there are only 7 mismatches which do not effectively change the structure or function of the WPRE or the resultant WPRE; and
SEQ ID NO: 34 was well-known as described by JS390642.
Claim 3 has been included because the sequences of Clark, Wang, and Nagase encoding SEQ ID NO: 1.
Claims 4-8 have been included because it does not further limit claim 1 which requires the sequence is “CpG-depleted”, because it is indefinite, and because some sequences have more CpGs than others.
Claims 9-10 have been included because Kerr (RU 2816871), Stanton (WO 2022226008), Riling (WO 2022165027), Esteves (20210381004), Stanton (WO 2021236479), Kerr (CA 3172572), and Kerr (20220119840) taught AAV2 and AAV9.
Claim 11 has been included because Kerr (RU 2816871), Stanton (WO 2022226008), Riling (WO 2022165027), Esteves (20210381004), Stanton (WO 2021236479), Kerr (CA 3172572), and Kerr (20220119840) taught an antibiotic resistance gene (see Materials and Methods).
Claim 12 has been included because Kerr (RU 2816871), Stanton (WO 2022226008), Riling (WO 2022165027), Esteves (20210381004), Stanton (WO 2021236479), Kerr (CA 3172572), and Kerr (20220119840) taught the antibiotic resistance gene was kanamycin, streptomycin, ampicillin, or neomycin (see Materials and Methods).
Thus, Applicants' claimed invention as a whole is prima facie obvious in the absence of evidence to the contrary.
The combined teachings of Kerr, Stanton, Riling, Esteves, Stanton, Kerr, and Kerr, Clark, Wang, Nagase, J5390642, JS5390508, JS53090481, Mehra, Ciuffi, and JS390642 did not teach the vector encoded kanamycin having a nucleic acid sequence that is at least 95% identical to SEQ ID NO: 21 as required in claim 13. The sequence was NOT well known. The closest sequence was described by GQ258349 which is 89.18% identical:
PNG
media_image18.png
222
810
media_image18.png
Greyscale
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.
Written Description
Claims 1-14 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 specification lacks written description for any sequence encoding an ITR that is at least 95% identical to SEQ ID NO: 40 other than SEQ ID NO: 40, any sequence encoding a CAG promoter that is at least 95% identical to SEQ ID NO: 48 other than SEQ ID NO: 48, any sequence encoding IFNβ that is at least 95% identical to SEQ ID NO: 4 other than SEQ ID NO: 4, any sequence encoding a WPRE that is at least 95% identical to SEQ ID NO: 33 other than SEQ ID NO: 33, or any sequence encoding a bGH polyA that is at least 95% identical to SEQ ID NO: 34 other than SEQ ID NO: 34 as required in claim 1 or at least 90% identical to SEQ ID NO: 21 in claim 13. The specification contemplates the genuses but does not provide a reasonable number of species within the genuses. The specification does not teach any species that have the same function within the genuses. Accordingly, the concepts lack written description.
The specification lacks written description for any “CpG-depleted” polynucleotide encoding IFNβ or antibiotic resistance gene as required in claim 1, 4-8, 14. The claim fails to provide any comparison as to what the CpG profile is being compared, i.e. a wild-type sequence. The specification contemplates the concept on pg 14-15 and throughout the specification without defining when a nucleic acid is depleted of CpGs. Pg 26-29 discusses “CpG dinucleotide modification” and contemplates how much CpG modification occurs without teaching what it means or how to accomplish “CpG-depletion” of nucleic acids or to what the “depletion” is being compared. Claims 4-8, 14 have been included because they discuss CpG modifications. Accordingly, the concept lacks written description.
The specification lacks written description for a “derivative thereof” of AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, … …AAV-HSV16 as required in claims 9, 10. The specification and the art at the time of filing do not teach any “derivatives” of AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, … …AAV-HSV16 as required in claims 9, 10. An AAV may be AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, … …AAV-HSV16, but it is unclear when an AAV is derived from AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, … …AAV-HSV16 as required in claims 9, 10. According the concept lacks written description.
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 1-14 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 metes and bounds of a “CpG-depleted” polynucleotide encoding IFNβ or antibiotic resistance gene in claim 1, 4-8, 14. The claim fails to provide any comparison as to what the CpG profile is being compared, i.e. a wild-type sequence, which makes it indefinite. The specification contemplates the concept on pg 14-15 and throughout the specification without defining when a nucleic acid is depleted of CpGs. Pg 26-29 discusses “CpG dinucleotide modification” and contemplates how much CpG modification occurs without teaching what it means or how to accomplish “CpG-depletion” of nucleic acids or to what the “depletion” is being compared. Claims 4-8, 14 have been included because they discuss CpG modifications. Accordingly, the concept is indefinite.
Claim 4 is indefinite because it is broader than claim 1. Claim 4 is limited to CpG-depleted nucleic acids while claim 4 says the sequence has “reduced CpG dinucleotides and/or increased methylation of CpG dinucleotides”. A sequence cannot be depleted of CpGs and have increased methylation of CpG dinucleotides at the same time. Claims 5-6 have been included because they relate to increased methylation.
Claims 7 and 14 are indefinite because the metes and bounds of a “parental equivalent” cannot be determined. The structures/functions of a “parental equivalent” cannot be determined from the specification or the art at the time of filing. The specification and the art do not define when/how a sequence is a “parental equivalent” on pg 26-29 in the discussion of “CpG dinucleotide modification”. Accordingly, those of skill would not be able to make the comparison or determine when they were infringing on the claims.
Claim 8 is indefinite because it does not further limit claim 1. Claim 8 required the CpG-dinucleotides are depleted, but claim 1 already requires the sequence encoding IFNβ is “CpG-deplete”. It is unclear if claim 8 is attempting to say something other than the sequence encoding IFNβ is “CpG-depleted”. If so, it is unclear what is being further limited. If not, then claim 8 does not further limit claim 1.
Conclusion
No claim is allowed.
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