DETAILED ACTION
The present application is being examined under the pre-AIA first to invent provisions.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 03/24/2025 has been entered.
Applicant’s arguments and amendments to the claims filed on March 24, 2025 have been received and entered Claims 13-20, 25 and 26 have been amended. Claims 13-26 are pending in the instant application
Election/Restrictions
Previous office action mailed on 11/27/2019 explicitly stated that claims 21-24 directed to an invention that is independent or distinct from the invention originally presented claims are drawn to product claims 13-20. Accordingly, claims 21-24 remain withdrawn from consideration as being directed to a non-elected invention. See 37 CFR 1.142(b) and MPEP § 821.03.
Priority
This application is a divisional of 12/734,016 filed on 05/28/2010, which is a 371 of PCT/EP2008/063297 filed on 10/03/2008 that claims priority from foreign application EP073011435.9, filed on 10/05/2007.
The disclosure of the prior-filed application, Application No. 09/119 EP073011435.9 fails to provide adequate support or enablement in the manner provided by the first paragraph of 35 U.S.C. 112 for one or more claims of this application. Instant claims 13-20, 25 and 26 are directed to a pharmaceutical dose for administration to a human subject of 1014 to 1016 viral genomes of a double- stranded self-complementary adeno-associated virus vector (scAAV vector) comprising an AAV9-derived capsid and a genome comprising a nucleic acid sequence encoding a survival of motor neuron (SMN) protein. The foreign application no., EP073011435.9 does not describe using 1014 to 1016 viral genomes of a double- stranded self-complementary adeno-associated virus vector (scAAV vector) comprising an AAV9-derived capsid as instantly claimed in the specification. Consequently, there is no written description in application EP073011435.9 for the 1014 to 1016 viral genomes of a double- stranded self-complementary adeno-associated virus vector (scAAV vector) comprising an AAV9-derived capsid as being claimed in this application. In case if applicants have evidence to support otherwise, applicants are invited to indicate page and line number for the written support specifically for said limitation. Therefore, the effective filing date for instant claims 13-20, 25 and 26 is 10/03/2008.
Claims 13-20, 25 and 26 are under consideration.
Maintained-Claim Rejections - 35 USC § 112-new matter-in modified form
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 13-20, 25 and 26 remain 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.
In the instant case, the recitation of limitation “a sterile pharmaceutical suspension of an AAV vector in liquid formulated as a single dose of 1014 to 1016 viral genomes of a double-stranded self-complementary adeno-associated virus vector (scAAV vector)….said suspension is capable of delivering the nucleic acid sequence and expressing the SMN protein in spinal cord motor neurons or glial cells of a human subject across an intact BBB” (claims 13 and 20) is considered new matter.
Upon further review of the instant specification, examiner could not find support for a pharmaceutical suspension of AAV vector in liquid formulated as a single dose in the claimed dose range that is capable of expressing the SMN protein in spinal cord motor neurons or glial cells of a human subject. There is no explicit or implicit support for any pharmaceutical suspension that is capable of expressing the specific protein (SMN protein) in specific cells (spinal cord motor neurons or glial cells of human. The specification lacks any direct or indirect support for using any pharmaceutical suspension of AAV vector capable of expressing the specific protein (SMN protein) in a specific cell (spinal cord motor neurons or glial cells) of a human subject (neonatal or adult) intended for pharmaceutical purposes. It is noted that instant specification clearly indicate that the invention is tailored for treating a variety of disorder but fails to disclose expression of SMN in any cells of CNS. In case if applicants have evidence to support otherwise, applicants are invited to indicate page and line number for the written support specifically for expressing SMN protein in motor neuron or glial cells as required by the instant application. Thus, at the time the application was filed, an Artisan of skill would not recognize from the disclosure that Applicant was in possession of a pharmaceutical suspension capable of expressing the SMN protein in spinal cord motor neurons or glial cells of a human subject across BBB, as claimed. Claims 14-19, 25 and 26 are included in the rejection because they directly or indirectly depend from the rejected base claim. This is a new matter rejection.
New-Claim Rejections - 35 USC § 112-written description
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 13-20, 25 and 26 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.
Claims are directed to a sterile pharmaceutical suspension of an AAV vector in liquid formulated as a single dose of 1014 to 1016 viral genomes of a double-stranded self-complementary adeno-associated virus vector (scAAV vector) for administration to a human subject, wherein said vector comprises a human AAV9 comprising an AAV9-derived capsid and a genome comprising a nucleic acid sequence encoding a survival of motor neuron (SMN) protein, wherein said suspension is capable of delivering the nucleic acid sequence and expressing the SMN protein in spinal cord motor neurons or glial cells of a human subject across an intact blood brain barrier
At issue for the purposes of written description is the structural feature(s) of the sterile pharmaceutical suspension that is functionally capable of delivering the nucleic acid sequence and expressing the SMN protein in spinal cord motor neurons or glial cells of a human subject across an intact blood brain barrier. The term pharmaceutical composition is interpreted in view of the teaching of the specification as suspension intended to treat SMA disorder by expressing SMN protein in human subject of any age.
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116. However, a showing of possession alone does not cure the lack of a written description. Enzo Biochem, Inc. v. Gen-Probe, Inc., 323 F.3d 956, 969-70, 63 USPQ2d 1609, 1617 (Fed. Cir. 2002) (see MPEP 2163).
The guidance provided in the specification is limited to preparing AAV2/9 vectors were generated by packaging AAV2 based recombinant self-complementary (sc) genomes in AAV1 and 9 capsids. The scAAV2/9 encoding mSeAP or GFP under the control of CMV promoter was used in subsequent experiments. The specification further discloses scAAV9-CMV-eGFP are injected into the jugular vein of one SMA-affected kitten. Example 5 teaches use of a dose of 3x10¹¹ vg or 1x10¹² vg per mouse of an AAV2/9 vector expressing the murine secreted alkaline phosphatase (mSEAP) under the control of the cytomegalovirus (CMV) promoter for expression in adult mice. Similar injections using scAAV9-GFP demonstrated the superiority of scAAV9 for systemic gene delivery to the spinal cord. A high number of cells were found to express four weeks after intravenous injection of 2x10¹² vg scAAV9, and GFP was expressed in the spinal cord in both neuronal and glial cells.
In the instant case, specification fails to provide adequate guidance on using any sterile pharmaceutical suspension of an AAV vector in liquid formulated as a single dose of 1014 to 1016 viral genomes of scAAV vector comprises a human AAV9 capsid that may or may not be flanked by AAV2 ITR expressing any specific protein ( SMN protein) under presence or absence of any promoter resulting in expression in motor neuron or glial cell of any human subject of any age. The specific viral vector (AAV2/9) encoding GFP or mSeAP under control of CMV promoter expressing reporter gene in motor neuron or glial cells does not support for a more generic AAV9 encoding a specific protein (SMN) capable of expressing in specific cells (SMN in spinal cord motor neuron or glial cells) of a human intended to treat a specific condition (SMA). It is relevant to point that instant specification discloses administration causing infection of motor neuron that express reporter protein (GFP or mSEAP) (see para. 10, 12, 106, fig. 11). However, the specification lacks any direct or indirect support for using any pharmaceutical suspension of AAV vector capable of expressing the SMN protein in spinal cord motor neurons or glial cells of a human subject to treat any condition. The art teaches reporter gene expression as exemplified in the instant application does not always correspond to functional transgene expression in relevant cells at an optimal level for it be used as a pharmaceutical. For instance, Schuster (Frontiers in Neuroanatomy, 2014, 10, 1-14) could not rule out the possibility of GFP expression being more widespread than the levels detectable by fluorescence using AAV9. It is possible that functionally relevant transgenes are effective at lower expression levels than those required for detection of reporter gene expression” (see page 11, col 1, para. 2). The disclosure suggest transgene [SMN} expression may not be at the same level as one observed with reporter gene like GFP. The specification does not provide any guidance with respect to expressing SMN using AAV9 in any model of SMA or cells at any level to make the suspension as pharmaceutical. Shahrukh et al (Gene Therapy, 2026, 1-9) in a recent repot indicated expression efficiency varies by transgene even in same liver tissue while using same AAV9 vector (see fig. 1). Van Alstyne et al ( Nature Neuroscience, 2021, 930-940) discloses AAV9 encoding GFP results in GFP expression in ChAT positive motor neuron, however, SMN overexpression using the same AAV9 vector results in cytoplasmic aggregation in same cells. These results suggest that even though motor neurons are identically infected but the SMN expression is different as compared to GFP (see page 933, col. 2, last 2 and 934, col. 1, para. 1-2). This is further supported by Besse (Molecular Therapy Vol. 28 No 8, 2020, 1887-1901) who reported “AAV9-mediated replacement of SMN in neurons using AAV9-SYN-SMN is not sufficient to rescue the SMA phenotype in SMNΔ7 mice. In contrast, the i.v. administration of AAV9-PGK-SMN resulted in better survival and phenotypic improvement of SMNΔ7 mice, even though the levels of SMN protein in the CNS organs and MN transduction were similar to those found after AAV9-SYN-SMN injection.” The Besse continue to teach that the SMN expression in neurons is necessary but not sufficient for the complete recovery of SMNΔ7 mice, suggesting that optimization is nevertheless needed to develop efficient gene replacement approaches for SMA (See page 1893, col. 2, para. 4 and 5). These studies further support that SMN expression is not necessarily proportional to the use of any promoter to rescue SMNΔ7 mice for the AAV suspension to be a pharmaceutical.
The claimed invention as a whole is not adequately described if the claims require essential elements which are not adequately described in the specification and which is not conventional in the art as of applicants effective filing date. Possession may be shown by actual reduction to practice, clear depiction of the invention in a detailed drawing or by describing the invention with sufficient relevant identifying characteristics such that a person skilled in the art would recognize that the inventor had possession of the claimed invention. Pfaff v. Wells Electronics. Inc., 48 USPQ2d 1641, 1646 (1998).
In In the instant case, it is apparent that applicant had possession of a method of intravascular delivery of AAV-GFP resulting in expression of reporter gene in motor neuron or glial cells establishing the neural tropism of AAV9 administered via intravascular route, however, neither specification nor prior art provided any guidance to reliably predict the expression of SMN protein at a level resulting in functional rescue in order for the sterile suspension to be a pharmaceutical. One of ordinary skill in the art would conclude that expression level of exemplified GFP in the instant specification could not be reasonably extrapolated to a specific gene (SMN) expression in a specific cell (motor neuron or glial cells).
An applicant shows possession of the claimed invention by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention. Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997).
Possession may also be shown in a variety of ways including description of an actual reduction to practice, or by showing that the invention was "ready for patenting" such as by the disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the applicant was in possession of the claimed invention. See, e.g., Pfaff v.Wells Elecs., Inc., 525 U.S. 55, 68, 119 S.Ct. 304, 312, 48 USPQ2d 1641, 1647 (1998), Regents of the University of California v. Eli Lilly, 119 F.3d 1559, 1568, 43 USPQ2d 1398, 1406 (Fed. Cir. 1997)*, Amgen, Inc. v. Chugai Pharmaceutical, 927 F.2d 1200, 1206, 18 USPQ2d 1016, 1021 (Fed. Cir. 1991) (one must define a compound by "whatever characteristics sufficiently distinguish it").
Therefore, conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. See Fiers v. Revel, 25 USPQ2d 1602 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481, 1483. In Fiddes, claims directed to mammalian FGF's were found to be unpatentable due to lack of written description for that broad class. The specification provided only the bovine sequence.
Accordingly, this limited information is not deemed sufficient to reasonably convey to
one skilled in the art that the applicant is in possession of the broad pharmaceutical suspension of different dose range of AAV9 encoding SMN under control of any promoter that is capable of delivering the nucleic acid sequence and expressing the SMN protein in spinal cord motor neurons or glial cells of a human subject across an intact blood brain barrier intended to treat any condition.
Response to arguments
Applicant disagrees with the rejection arguing specification provides adequate support for a dosage that would have been expected to (i) enter into cells and (ii) express the functional protein. Applicant's working examples support that such a single dose of 10¹⁴ to 10¹⁶ viral genomes would be an effective dose in humans. For example, in Example 5, Applicant used a dose of 3x10¹¹ vg or 1x10¹² vg per mouse of an AAV9 vector expressing the murine secreted alkaline phosphatase (mSEAP) under the control of the cytomegalovirus (CMV) promoter for expression in adult mice. Similar injections using scAAV9-GFP demonstrated the superiority of scAAV9 for systemic gene delivery to the spinal cord. A high number of cells were found to express four weeks after i.v injection of 2x10¹² vg scAAV9, and GFP was expressed in the spinal cord in both neuronal and glial cells. Thus, the skilled artisan would have understood that a dose of 3x10¹¹ to 2x10¹² vg scAAV9 was a sufficient dose to provide for widespread delivery and expression of a transgene in an adult mouse. Applicant in part rely on example 5 to assert that based on Applicant's results in mice, the skilled artisan would have expected that a dosage of 10¹⁴ to 10¹⁶ would provide a sufficient dose to provide for widespread delivery and expression of a transgene, such as SMN, in a human. Applicant in part rely on Paragraph [0064] of the published application supports that the invention can be used to deliver the "survival of motor neuron" protein (SMN) into CNS cells including the motor neurons. Thus, the provision of some level of SMN transgene expression from Applicant's vector would have been expected to have some effect on SMN protein levels in a patient with SMA. Since low SMN protein levels are associated with disease, the skilled artisan would have expected that an increase in SMN levels would be provide a benefit. Applicants’ arguments have been fully considered, but are not found persuasive.
In response, it is emphasized that instant rejection is a new matter rejection. MPEP 2163.06 states “Matter not present on the filing date of the application in the specification, claims, or drawings that is added after the application filing is usually new matter. As stated in previous office action, in the instant case, intravenous injection of 2x10¹² vg scAAV9- GFP resulting in expression of GFP in both neuronal and glial cell does not support the recitation of a suspension capable of delivering the nucleic acid sequence and expressing the SMN protein in spinal cord motor neurons or glial cells of a human subject across an intact blood brain barrier.
Applicant’s argument stating “skilled artisan would have expected that a dosage of 10¹⁴ to 10¹⁶ would provide a sufficient dose to provide for widespread delivery and expression of a transgene, such as SMN, in a human” itself suggest recitation of result recited in the claim is expected or anticipated result, however, the specification fails to implicitly or explicitly disclose expressing the SMN protein in spinal cord motor neurons or glial cells of a human subject (adult or neonatal).
The mere fact that a certain thing may result from a given set of circumstances [in the instant case anticipated or expected results based on GFP] is not sufficient.’" In re Robertson, 169 F.3d 743, 745, 49 USPQ2d 1949, 1950-51 (Fed. Cir. 1999) (citations omitted).
As emphasized in the previous office action, the claimed dosage may be enough to (i) enter into cells or (ii) infect the cells, but that may not be necessarily enough for expression of the functional protein such as SMN that could be due to transgene silencing (epigenetic silencing), poor promoter activity, protein degradation, low transcription or translation efficiency. This is because SMN protein expression level cannot be inferred from reporter gene expression because SMN is controlled by splicing, RNA processing (see Groen et al Human Molecular Genetics, 2018, Vol. 27, No. 16, 2851–2862, cited as evidence and also see written description rejection above).
In view of foregoing, it is apparent that instant specification fails to teach a suspension that is formulated as a single dose that is specific to any disease (SMA) for expression of a specific protein such as SMN protein in spinal cord motor neurons or glial cells as claimed. Therefore, instant new matter rejection is maintained for the reasons of record.
On page 5 of the applicant’s argument, applicant assert that Inagaki et al. did not indicate the precise number of positive cells in brain, but only that the numbers of b-galactosidase-expressing cells were much less than those in the other 4 tissues (i.e., liver, skeletal muscle, heart, and pancreas) even at the highest vector dose, indicating poor transduction. Based on the experiments in Inagaki one would conclude that AAV9 could not cross the blood-brain barrier. (Id. at 120.) Based on Inagaki et al., the skilled artisan would not have expected that AAV9 could cross the blood-brain barrier. Applicant's success in demonstrating doses sufficient to provide for widespread delivery and expression of a transgene in an adult mouse would have been sufficient for the skilled artisan to conclude the Applicant had possession of the claimed invention.
In response, it is emphasized that the Inagaki (Mol. Therapeutic, 2006, 14, 45-51, art of record, cited as evidence by applicant) was cited in response to applicant’s argument that showed intravenous injection of ds AAV9 vector into mice resulted in substantial vector genome in various tissues, however, many non-hepatic tissues including the brain and spinal cord did not express the detectable level of transgene product despite presence of vector genome (see page 51, col. 1, para. 2, also see Fontaine’s declaration filed on November 21, 2018, section 8). This is further supported by Byrne (WO/2008103993, 8/28/2008, filed 2/23/2007) who reported intravenous injection of same dose range of AAV9 encoding b-gal to a subject, but lacked guidance on injecting dose range for expression of a specific protein, namely SMN protein, in specific cells, namely spinal cord motor neurons or glial cells of a human (see applicant’s argument page 8, para. 2 dated 05/30/2024). It is in this context, it was stated that applicant has also not shown expression of the specific protein, namely SMN protein, in specific cells, namely spinal cord motor neurons or glial cells of a human in order for the sterile suspension to a pharmaceutical suspension.
In view of foregoing, it is apparent that applicant’s argument of instant specification supporting optimal transduction or substantial infection (presence of vector genome) does not necessarily support for expression of a specific protein (SMN protein) in a specific cell (spinal cord motor neuron or glial cells) as required by the claim that was previously argued by applicant in order to overcome obviousness rejection.
Conclusion
Examiner’s note: It should be noted that an interview in the instant application was held on December 5, 2025 between Examiner Singh and applicant’s representative Mr. Salvatore Arrigo. The interview summary was inadvertently sent to related application no 12734016. Examiner apologizes for the oversight. The issues discussed during the interview is reproduced below:
Applicant's representative contacted the office to discuss rejection of record. The issue of new matter pertaining to the limitation of said dose is capable of expressing the SMN protein in spinal cord motor neurons or glial cells of a human subject across an intact blood brain barrier" was discussed. Examiner pointed out page 5 of the final office action mailed on 06/18/2025 to support the fact that claimed dosage may be enough for AAV to (i) enter into cells or (ii) infect the cells, but that may not be necessarily enough for expressing the functional protein that could be due to transgene silencing (epigenetic silencing), poor promoter activity, protein degradation, low transcription or translation efficiency. It is in this context; Inagaki reference and applicant's declaration was cited in the final office action that was discussed. Applicant would consider providing evidence and/or declaration to support the claimed dose range in the formulation is capable of expressing SMN in motor neuron or glial cells and also point out the support for the limitation in the specification. Applicant's representative would also consider amending claim to a more specific composition with specific promoter as set forth in claim 20. No agreement was reached.
No claims allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Byrne (WO/2008103993, 8/28/2008, filed 2/23/2007), as evidenced by Inagaki et al (Molecular Therapy, 2006, 14 (1), 45-53, art of record) and Nakai (J Virol., 2005,79:214-224, IDS) and further in view of Samulski et al (US 7,465,583, IDS) and Mazarakis (US 2004/0076613, IDS) as evidence by Cearlay et al (Molecular Therapy (2006) 13, 528-537, art of record). Prior art fails to teach or suggest a dose range that is specific to any disease or for expression of a specific protein, namely SMN protein, in specific cells, namely spinal cord motor neurons or glial cells of a human is found persuasive.
Akache, B. et al. (J. Virol. 80, 9831–9836 (2006)) teach AAV9 uses the same laminin receptor, as do AAV2 and AAV8.
Kaspar et al (Science, 2003, 5634, 839-845, IDS) teach peripheral injection of 1010 vg/mouse of AAV encoding GFP, IGF1 or GDNF shows transport of virus to the lumbar spinal cord infecting spinal motor neuron (see fig. 1).
Bostick et al (Gene Therapy (2007) 14, 1605–1609) teaches intravenous injection 1x1012 vg of AAV to a mouse (20g) (see page 1605, col. 2, last para).
Schnepp and Clark ((2002) highly purified recombinant adeno-associated virus vector, page 427 in Methods in Molecular Medicine vol. 69, Gene therapy protocols 2ed Edited by JR Morgan.) teaches based on large animal studies, a clinical dose in human will require 1012 to 1014 rAAV particle depending on the level of therapeutic protein expression needed for treatment efficacy (see page 427).
Janson et al (HUMAN GENE THERAPY 13:1391–1412, 2002) teaches delivering 900 microliters of AAV to a human brain.
Crystal (HUMAN GENE THERAPY 15:1131–1154, 2004)
Pacak et al (Circulation Res. 2006, 99, e3-e9, IDS) teaches systemic venous (temporal or jugular vein) administration of rAAV2/8 and rAAV2/9 carrying the CMV-lacZ gene construct followed by histological analysis and X-gal staining using the B-galactosidase enzyme detection assay to detect lacZ expression (pp. e4-e5, e7-8, Figure 2). The vectors were administered in an effective amount, particularly, 1.0x 1011 vg. The results showed that whereas rAAV2/8 and rAAV2/9 are able to transduce tissues such as brain, lung and kidney, there is less transduction of spleen and small intestine (p. e5). Pacak also notes the ability of rAAV2/9 to successfully pass through the vasculature and transduce cells following intravenous administration (p. e8). Similar experimentation was carried out in nonhuman primates, showing similar results (e4, e7). Pacak’s administration also applies to the claims as an AAV9 vector construction of the term AAV vectors as including constructions of different AAV species as well as constructs with AAV2-derived genomes in an AAV9-derived capsid specifically (‘574 6:55-57, claims 6, 15).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ANOOP K. SINGH whose telephone number is (571)272-3306. The examiner can normally be reached Monday-Friday, 8AM-5PM.
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/ANOOP K SINGH/ Primary Examiner, Art Unit 1632
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