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 Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 21 and 27 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 21 depends on claim 20 and adds a limitation of antisense, siRNAs and short hairpin RNAs targeting LRP1 RNA of the cells of the central nervous system. Claim 20 already recites the same antisense, siRNAs and short hairpin RNAs, which has to inhibit expression of LRP1, therefore they must target LRP1 RNA. That means that claim 21 does not further limit claim 20.
Claim 27 depends on claim 26 and adds a limitation of CRISPR guide RNA targeting LRP1 DNA of the cells of the central nervous system. Claim 26 already recite that CRISPR guide RNA has to disrupt expression of LRP1, meaning that such guide RNA has to target LRP1 DNA. Thus, claim 27 does not further limit claim 26.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 18-21, 32-35 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Liaudet et al (WO 2009/043858, April 2009).
Concerning claims 18-21 Liaudet disclose method of treatment of Alzheimer’s disease by administering inhibitor of expression of LRP1 (see lines 4-6 on page 4), which can be antisense oligonucleotides and siRNAs (see lines 14-30 on page 19). Alzheimer’s disease is a type of tauopathy according to Abstract of instant specification. Such siRNA targets LRP1 mRNA (see lines 5-10 on page 20).
Concerning claims 32-35 Liaudet disclose that antisense oligonucleotides and siRNAs can be delivered by a vector (see lines 11-12 on page 21), such vector can be plasmid delivered by gold or liposomal particle (see bridging paragraph between pages 22-23). Alternatively, vector can be adeno-associated virus (see lines 10-25 on page 21).
Claim(s) 18-21, 32-35 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Gonias et al (US 2014/0161807, June 2014).
Concerning claims 18-21 Gonias disclose method of treatment of Alzheimer’s disease by administering inhibitor of LRP1 (see paragraphs [0012, 0020, 0074]), which can be inhibitory nucleic acid such as antisense oligonucleotides, siRNAs and shRNAs (see paragraph [0018]). Alzheimer’s disease is a type of tauopathy according to Abstract of instant specification. Such siRNA targets LRP1 mRNA (see paragraph [0107]).
Concerning claims 32-33 Gonias disclose that antisense oligonucleotides, siRNAs and shRNAs can be delivered by a liposomal particle (see paragraph [0108]).
Concerning claims 34-35 Gonias disclose that antisense oligonucleotides, siRNAs and shRNAs can be delivered by a viral vector (see paragraph [0018]), such vector can be adeno-associated virus (see paragraph [0112]).
Claim(s) 18-25, 32, 34-35 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Rauch et al (Nature, published online 1 April 2020, vol.580, pages 381-393).
Concerning claims 18-25, 32, 34-35 Rauch disclose method of treatment of tauopathy in a subject comprising administering shRNA identical to instant SEQ ID NO: 3 targeting LRP1, which is delivered by adeno-associated virus (see Abstract, Figure 4, “AAV production and purification” section on page 386).
Claim Rejections - 35 USC § 103
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.
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.
Claim(s) 18-25 is/are rejected under 35 U.S.C. 103 as being unpatentable over Liaudet et al, above, as applied to claims 18-21, and in further view of Gerdes et al (WO 2011/054644, May 2011).
Teachings of Liaudet are discussed above.
Liaudet do not teach expression of short hairpin RNA with 99% identity to instant SEQ ID NO: 3.
Gerdes teach design of siRNAs targeting LRP1 (see lines 20-33 on page 10). They teach that siRNA can be double-stranded or single-stranded forming hairpin structures comprising duplex region, short hairpin RNA (see lines 10-20 on page 90) and teach methods for designing such RNAs (see lines 25-30 on page 90) using available on-line tools (see lines 8-17 on page 91).
It would have been obvious to one of the ordinary skill in the art before the effective filing date of the claimed invention to design short hairpin RNA targeting LRP1 based on teachings of Gerdes to express in the methods of Liaudet. One of the ordinary skill in the art would be motivated to do so, because Gerdes teach methods of designing short hairpin RNAs targeting LRP1, which allow design of a number of such RNAs, including one of instant SEQ ID NO: 3. Further, such RNA can be expressed from vectors taught by Liaudet for disease treatment as taught by Liaudet.
Claim(s) 18-21, 26-31 is/are rejected under 35 U.S.C. 103 as being unpatentable over Liaudet et al, above, as applied to claims 18-21, and in further view of Luo et al (Cell Reports, 2018, 24: 3033-3044 and Supplemental Information), Gilbert et al (US 2017/0204407, July 2017) and GenBank X13916.1 (GenBank X13916.1, 1996, pages 1-8)
Teachings of Liaudet are discussed above.
Liaudet do not teach administration of CRISPR guide RNA comprising instant SEQ ID NO: 5 in combination with Cas9.
Luo teach a method of disrupting LRP1 gene using CRISPR/Cas9 system (see Abstract, Figure 6). Design of such system comprising guide RNA is further described in Supplemental Information on page 11.
Gilbert teach methods of gene disruption using CRISPR/Cas9 systems (see Abstract, paragraph [0006]). Gilbert teach a large number of guide RNA targeting a variety of genes (see paragraph [0024]), wherein guide RNA of SEQ ID NO: 98017 (see sequence listing) is 100% identical to instant SEQ ID NO: 5. Such sequence is identical to nucleotides 27-45 of human mRNA for LRP1 as evidenced by GenBank X13916.1 mRNA sequence of LRP1 on page 3, meaning that this guide RNA targets LRP1.
It would have been obvious to one of the ordinary skill in the art before the effective filing date of the claimed invention to administer CRISPR/Cas9 system comprising guide RNA targeting LRP1 taught by Luo and Gilbert for treatment of Alzheimer’s disease as taught by Liaudet, arriving at instant invention. One of the ordinary skill in the art would be motivated to do so because Liaudet teach disruption of LRP1 gene for Alzheimer’s disease treatment and Luo and Gilbert provide new effective systems for LRP1 gene disruption.
Claim(s) 18-25 is/are rejected under 35 U.S.C. 103 as being unpatentable over Gonias et al, above, as applied to claims 18-21, and in further view of Gerdes et al (WO 2011/054644, May 2011).
Teachings of Gonias are discussed above.
Gonias do not teach expression of short hairpin RNA with 99% identity to instant SEQ ID NO: 3.
Gerdes teach design of siRNAs targeting LRP1 (see lines 20-33 on page 10). They teach that siRNA can be double-stranded or single-stranded forming hairpin structures comprising duplex region, short hairpin RNA (see lines 10-20 on page 90) and teach methods for designing such RNAs (see lines 25-30 on page 90) using available on-line tools (see lines 8-17 on page 91).
It would have been obvious to one of the ordinary skill in the art before the effective filing date of the claimed invention to design short hairpin RNA targeting LRP1 based on teachings of Gerdes to express in the methods of Gonias. One of the ordinary skill in the art would be motivated to do so, because Gerdes teach methods of designing short hairpin RNAs targeting LRP1, which allow design of a number of such RNAs, including one of instant SEQ ID NO: 3. Further, such RNA can be expressed from vectors taught by Gonias for disease treatment as taught by Gonias.
Claim(s) 18-21, 26-31 is/are rejected under 35 U.S.C. 103 as being unpatentable over Gonias et al, above, as applied to claims 18-21, and in further view of Luo et al (Cell Reports, 2018, 24: 3033-3044), Gilbert et al (US 2017/0204407, July 2017) and GenBank X13916.1 (GenBank X13916.1, pages 1-8)
Teachings of Gonias are discussed above.
Gonias do not teach administration of CRISPR guide RNA comprising instant SEQ ID NO: 5 in combination with Cas9.
Luo teach a method of disrupting LRP1 gene using CRISPR/Cas9 system (see Abstract, Figure 6). Design of such system comprising guide RNA is further described in Supplemental Information on page 11.
Gilbert teach methods of gene disruption using CRISPR/Cas9 systems (see Abstract, paragraph [0006]). Gilbert teach a large number of guide RNA targeting a variety of genes (see paragraph [0024]), wherein guide RNA of SEQ ID NO: 98017 (see sequence listing) is 100% identical to instant SEQ ID NO: 5. Such sequence is identical to nucleotides 27-45 of human mRNA for LRP1 as evidenced by GenBank X13916.1 mRNA sequence of LRP1 on page 3, meaning that this guide RNA targets LRP1.
It would have been obvious to one of the ordinary skill in the art before the effective filing date of the claimed invention to administer CRISPR/Cas9 system comprising guide RNA targeting LRP1 taught by Luo and Gilbert for treatment of Alzheimer’s disease as taught by Gonias, arriving at instant invention. One of the ordinary skill in the art would be motivated to do so because Gonias teach disruption of LRP1 gene for Alzheimer’s disease treatment and Luo and Gilbert provide new effective systems for LRP1 gene disruption.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to EKATERINA POLIAKOVA whose telephone number is (571)270-5257. The examiner can normally be reached Mon-Fri 8-5.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jennifer Dunston can be reached at (571)272-2916. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/EKATERINA POLIAKOVA-GEORGANTAS/Primary Examiner, Art Unit 1637
Prosecution Insights