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 .
Priority
Applicants claim for priority to a provisional application 63/265,429 is acknowledged. The effective filing date for claims 83, 96-104 is December 15, 2021.
Application Status
In view of further search and consideration, the previous Non-Final Office Action is withdrawn. The instant action presented is a second action Non-final Office Action. The following rejections are applicable, and are not necessitated by Applicant’s amendments.
Status of the Claims
In the response filed December 27, 2025, Applicants have cancelled claims 1-82 and 84-95, and have presented claims 83, and 96-104.
Claims 83, and 96-104 are under examination in this Office Action.
Information Disclosure Statement
Applicant is reminded that the listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Withdrawn Objections & Rejections
Rejections and/or objections not reiterated from the previous office action are hereby withdrawn due to amendment. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Claim Interpretation
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art.
The specification recites: “As used herein, the term "about," when in reference to a value or parameter wherein, includes a variability of ± 1% of the value or parameter. For example, when referring to a pH value, "about" refers to a range that includes the value 1% below the referenced value, and the value 1% above the referenced value. Thus, a pH of about 10 refers to a pH that encompasses a pH of 9.9 to a pH of 10.1, inclusive (See specification para. 69). Therefore, the term “about” will be referenced as referring to the DMSO range of 0.1% as a range that includes the value 0.099% below the referenced value (1% of 0.1 is 0.001, thus 0.1 minus .001 is 0.099), and the above the referenced value of 0.1% DMSO as the value of 0.101% DMSO).
Claim Rejections - 35 USC § 102
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 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 83, 96-99, 101-103 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Schaffer et al., (WO2021/221956A1, published Nov. 2021)
This is a new rejection in response to Applicants arguments filed on Dec. 27, 2025.
Regarding claim 83, Schaffer discloses a method for producing recombinant AAV (rAAV) particles comprising: (a) culturing a mammalian cell (e.g. HEK293 cells) comprising one or more polynucleotides comprising an rAAV genome in a culture medium where the culture medium does not comprise dimethyl sulfoxide (DMSO)(see e.g. pages 10, 24-26, fig. 2, Example 1); and Schaffer discloses (b) culturing the mammalian cell in a second culture medium with a blocking agent (i.e. DMSO), wherein the second culture medium comprises about 0.1% to about 5% dimethyl sulfoxide (DMSO)(i.e. 100mM of DMSO is ((0.1molx78.13g/mol)/(1.10g/mL)= 7.10mL where (7.10mL/1000mL)x100=0.71%)(see e.g. pages 10, 24-26, fig. 2, Example 1). Further, Schaffer discloses wherein the mammalian cell is an AAV producer cell; thereby producing rAAV particles (see e.g. pages 10, 24-26, fig. 2, Example 1).
Regarding claim 96, Schaffer discloses wherein the culturing in step (a) is for about 1 hour to about 48 hours (see e.g. pages 10, 24-26, fig. 2, Example 1).
Regarding claim 97, Schaffer discloses wherein the culturing in step (b) is for about 1 hour to about 100 hours (i.e. 96 hours or more)(see e.g. pages 10, 24-26, fig. 2, Example 1).
Regarding claim 98, Schaffer discloses introducing into the mammalian cell prior to step (b) a polynucleotide encoding an AAV capsid protein, a polynucleotide encoding an AAV Rep protein, and a polynucleotide encoding one or more helper virus genes (see e.g. pages 10, 16, 24-26, fig. 2, Example 1).
Regarding claim 99, Schaffer discloses purifying the rAAV particles (see e.g. pages 10, 16, 24-26, 29, fig. 2, Example 1, claim 12).
Regarding claim 101-102, Schaffer discloses wherein the rAAV genome comprises a transgene encoding a polypeptide, guide (gRNA), and interfering RNA’s siRNA, and miRNA (see e.g. pages 10, 14, 16, 20, 24-26, 29, fig. 2, Example 1, claim 12).
Regarding claim 103, Schaffer discloses wherein the rAAV genome comprises a 5' inverted terminal repeat (5' ITR) nucleotide sequence 5' of the trans gene and a 3' inverted terminal repeat (3' ITR) nucleotide sequence 3' of the transgene (see e.g. pages 1-10, 14, 16, 20, 24-26, 29, fig. 2, Example 1, claim 12).
Therefore, the prior art of Schaffer anticipates the instant claims.
Claim 83, 96-99, 101-102 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Yu et al., (WO2020/172624 A1, published Aug. 2020, prior art of record).
This is a new rejection in response to Applicants arguments filed on Dec. 27, 2025, and therefore any aspect of applicant's response considered relevant to the new rejection as newly set forth is responded to following the statement of rejection.
Regarding claim 83, Yu discloses a method for producing recombinant AAV (rAAV) particles comprising: (a) culturing a mammalian cell (e.g. HEK293 cells) comprising one or more polynucleotides comprising an rAAV genome in a culture medium where the culture medium does not comprise dimethyl sulfoxide (DMSO)(see e.g. page 3, 32-34, and Examples 1-5). Yu discloses (b) culturing the mammalian cell in a second culture medium with an AAV-enhancer (i.e. nocodazole-DMSO), wherein the AAV enhancers is added at about 1% v/v per flask which reads on the second culture medium comprises about 0.1% to about 5% comprising dimethyl sulfoxide (DMSO)(see e.g. page 3, 32-34, Example 1-5). Further, Yu discloses wherein the mammalian cell is an AAV producer cell; thereby producing rAAV particles (see e.g. para. 12, page 3, 32-34, Example 1-5, and figs 1-3).
Regarding claim 96, Yu discloses wherein the culturing in step (a) is for about 0.5 hours (see e.g. para. 12, page 3, 32-34, Example 1-5, and figs 1-3).
Regarding claim 97, Yu discloses wherein the culturing in step (b) is for about 15.5 hours, corresponding to the claim limitation of about 1 to 100 hours (see e.g. para. 12, page 3, 32-34, Example 1-5, and figs 1-3).
Regarding claim 98, Yu discloses introducing into the mammalian cell prior to step (b) a polynucleotide encoding an AAV capsid protein and a polynucleotide encoding an AAV Rep protein (i.e. rep/cap plasmid, pRC), and a polynucleotide encoding one or more helper virus genes (i.e. pHelper plasmid)(see e.g. para. 12, page 3-14, 32-34, 40-41, Example 1-5, and figs 1-3).
Regarding claim 99, Yu discloses purifying the rAAV particles (e.g. diatomaceous earth filtration, DE filtration)(see e.g. para. 12, page 3-14, 30-34, 40-41, Example 1-5, and figs 1-3, 14).
Regarding claim 101-102, Yu discloses wherein the rAAV genome comprises a transgene encoding a polypeptide (see e.g. para. 12, page 3-14, 30-34, 40-41, Example 1-5, claims 11, 13, 40, and figs 1-3, 14).
Regarding claim 104, Yu discloses the rAAV particles comprises up to about 2 x 1011 of viral genomes per milliliter (mg/ml) which reads on the claim limitation of at least about 1 x 1015 viral genomes (see e.g. abstract, para. 12, page 3-14, 30-34, 40-41, Example 1-5, claims 11, 13, 40, 25, and 50-51, figs. 1, 3, 11 and 14).
Therefore, the prior art of Yu anticipates the instant claims.
Response to Traversal:
Applicant argues that the prior art of Yu mentions DMSO once in the entire document, and that DMSO is mentioned in combination with nocodazole (Remarks, page 4-5).
Applicant arguments are acknowledged, have been fully considered, and have been deemed unpersuasive.
In response to Applicants argument that DMSO is only mentioned once (see para. 12 of Yu), it is noted that the preferred embodiments are not the only teaching of a reference. “The use of patents as references is not limited to what the patentees describe as their own inventions or to the problems with which they are concerned. They are part of the literature of the art, relevant for all they contain.” In re Heck, 699 F.2d 1331, 1332-33, 216 USPQ 1038, 1039 (Fed. Cir. 1983) (quoting In re Lemelson, 397 F.2d 1006, 1009, 158 USPQ 275, 277 (CCPA 1968)). A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill the art, including nonpreferred embodiments. Merck & Co. v. Biocraft Laboratories, 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989). Further, it is noted that the MPEP 2123 (I) states that patents are relevant as prior art for all they contain, and that a reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill the art, including nonpreferred embodiments.
In the instant case, the citations of Yu are cited as “see for example”(e.g.) and the disclosures are referencing parts of Yu that discloses using an AAV-enhancer. As discussed above, Yu discloses that an AAV-enhancer may be nocodazole-DMSO (see para. 12). It is noted in the Examples of Yu, that Yu does not teach the identify of the AAV-enhancer. Therefore, it is reasonable that a person of ordinary skill in the art would be able use any AAV-enhancer listed in Yu (e.g. para. 12), and that AAV-enhancer would be used in the instant method of Yu (see e.g. Examples 1, 3, and 7). In response to Applicants argument regarding Yu disclosing nocodazole-DMSO, it is noted that claims read on “comprising” (see MPEP 2111.03). In the instant case, the claims do not exclude other embodiments, such as the addition of nocodazole-DMSO.
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.
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.
Claims 83 and 96-104 are rejected under 35 U.S.C. 103 as being unpatentable over Lee et al., (WO2015/031686 A1, published 2015, prior art of record), Yu et al., (WO2020/172624 A1, published Aug. 2020, prior art of record), Lynch, Janet, et al. (Journal of neuroscience methods 350: 109058, published 2020, prior art of record), and Mejza (U.S. Patent US6416992B1; Application No. 09/417,418, published 2002; prior art of record).
This is a new rejection in response to Applicants arguments filed on Dec. 27, 2025, and therefore any aspect of applicant's response considered relevant to the new rejection as newly set forth is responded to following the statement of rejection.
Regarding claim 83, Lee discloses methods for producing recombinant AAV (rAAV) particles (see e.g. abstract and para. 53). Lee discloses culturing a mammalian cell (e.g. HEK293 cells) comprising one or more polynucleotides comprising an rAAV genome (i.e. rAAV2.8) in a culture medium (see e.g. para. 20-26, 61, 112, 183, Examples 1), where the culture medium does not comprise dimethyl sulfoxide (DMSO)(see e.g. page 58-61, Example 1). Lee discloses culturing the mammalian cell in a second culture medium comprising a AAV production enhancer like sodium butyrate (see e.g. 76, 183, page 27, 58, Examples 1, fig. 10-11), wherein the mammalian cell is an AAV producer cell; thereby producing rAAV particles (see e.g. Examples 1-2, pages 57-75). Further, Lee discloses that at large scale (e.g., 1 liter), 0.5% (w/v) protein hydrolysate and 5 mM of the AAV production enhancer sodium butyrate increased yield of rAAV particles (see e.g. para. 76).
Lee is silent regarding the second culture medium comprising dimethyl sulfoxide (DMSO) and the percentage of DMSO.
However, the prior art of Yu discloses culturing mammalian cells (i.e. HEK293 cells) with AAV production enhancer like sodium butyrate or Nocodazole-DMSO (see e.g. para. 12-18, 89, 95, 98, 102, 115, 120, 124, 131, Examples 1-7, fig. 1, 7). Further, Yu discloses that the AAV enhancers Nocodazole-DMSO may be added at about 1% v/v per flask (see e.g. page 37), which reads on the claimed about 0.1 (v/v) to about 5% (v/v). Additionally, the prior art of Lynch discloses treating mammalian (i.e. HEK293) cells with dimethyl sulfoxide (DMSO) solution at 5% (v/v)(see e.g. Fig. 2, page 6).
Accordingly, it would have been obvious to one of ordinary skill in the art to have modified the methods for producing recombinant AAV as taught by Lee with incorporating the AAV production enhancers as taught by Yu because both Lee and Yu disclose using AAV enhancers like sodium butyrate or Nocodazole-DMSO. It would have been obvious for a person of ordinary skill in the art to substitute one known AAV production enhancer (i.e. sodium butyrate) as taught by Lee for another a AAV production enhancer (i.e. DMSO) as taught by Yu, which would have led to predictable results with a reasonable expectation of success because both Lee and Yu teach methods for increasing the yield of rAAV particles (see e.g. abstracts, respectively). Additionally, the prior art of Lynch discloses that protein expression yield in human embryonic kidney cells (i.e. HEK293) could be enhanced with a brief treatment of dimethyl sulfoxide (DMSO) solution (see e.g. title and abstract). Further, Lynch discloses treating mammalian (i.e. HEK293) cells with dimethyl sulfoxide (DMSO) solution at 5% (v/v)(see e.g. Fig. 2, page 6). Thus, a person of ordinary skill could have substituted one AAV production enhancer for another with predictable results and a reasonable expectation of success, since Lee, Yu, and Lynch disclose methods involving mammalian HEK293 cells and DMSO, which are readily available and deliverable using similar techniques.
Regarding claim 96, Lee discloses wherein the culturing in step (a) is for about 15 minutes (see e.g. page 58, para. 183-184).
Lee does not explicitly state wherein the culturing in step (a) is for about 0.5 hours (i.e. 30 minutes) to about 5 hours.
However, the prior art of Mejza teaches wherein the culturing in step (a) is for about 3-4 hours (see e.g. col. 17-18, Transfection Protocol, and col. 18, para. 2), corresponding to the claimed limitation range of about 0.5 to about 5 hours.
In regards to ranges, MPEP 2144.05(I) states, “In the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990)”, continuing in regards to ranges are close, “Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985)”. In the instant case, neither the specification nor Applicant have provided evidence of that the culture time in step (a) of “about 0.5 to about 5 hours” is critical, thus the teachings by Lee and Mejza renders the claimed percentage obvious.
Accordingly, it would have been obvious to one of ordinary skill in the art to have modified the methods for producing recombinant AAV particles as taught by Lee with incorporating the first culture time period of about 0.5 to about 5 hours as taught by Mejza because person of ordinary skill in the arts could have arrived at the time range by routine optimization. Further, an artisan of ordinary skill in the art of culturing methods with HEK293 cells and rAAV particles has good reason to pursue the known options within his or her technical grasp (KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (US 2007). In the instant case, a person of ordinary skill in the art would have had a predictable result with a reasonable expectation of success of optimizing the time period to be about 0.5 to about 5 hours because both Lee and Mejza teach recombinant AAV methods with HEK293 cell cultures.
Regarding claim 97, Lee discloses wherein the culturing in step (b) is for about 24 hours (see e.g. page 58), corresponding to the claim limitation of about 1 to 100 hours.
Regarding claim 98, Lee discloses comprising introducing into the mammalian cell prior to step (b) a polynucleotide encoding an AAV capsid protein, a polynucleotide encoding an AAV Rep protein, and a polynucleotide encoding one or more helper virus genes (see e.g. para. 28, 55-68, page 41-42, 55-56, Examples 1-2).
Regarding claim 99, Lee discloses comprising purifying the rAAV particle by chromatography (see e.g. para. 28, 55-68, page 41-42, 55-56, and 164,Examples 1-2).
Regarding claim 100, Lee discloses varying the AAV composition concentration for a human patient who may ultimately receive the rAAV particles in gene therapy (see e.g. para. 113), which reads on the claim limitation of formulating for administration of rAAV particles to a human subject. Additionally, this is the intended use of the claimed composition and does not necessarily change the structure of the composition beyond being in a sterile formulation. Since Lee teaches that the AAV composition is to be administered to a patient for gene therapy purposes (e.g. para. 113), it would have been obvious to combine the AAV composition into a formulation for human administration.
Regarding claim 101-102, Lee discloses wherein the rAAV genome comprises a transgene encoding a polypeptide, antisense RNA, shRNA, or ribozyme (see e.g. para. 13, 54, 84-85, 88-89, 93, page 36-39).
Regarding claim 103, Lee discloses wherein the rAAV genome comprises a 5' inverted terminal repeat (5' ITR) nucleotide sequence 5' of the trans gene and a 3' inverted terminal repeat (3' ITR) nucleotide sequence 3' of the trans gene (see e.g. para, 8, 12, and 62-63 page 19-21, 56, 76, claim 1).
Regarding claim 104, Lee discloses producing recombinant AAV particles in HEK293 cells with improved parameter values that include higher cell density at least about 2.5 x 106 cells/ml (see e.g. paras. 29-30 and 212, and claim 6).
Lee does not explicitly state the amount of viral genomes.
However, the prior art of Yu discloses the rAAV particles comprises up to about 2 x 1011 of viral genomes per milliliter (mg/ml) which reads on the claim limitation of at least about 1 x 1015 viral genomes (see e.g. abstract, para. 6-10, 44, 110, claims 25, and 50-51).
Accordingly, it would have been obvious to one of ordinary skill in the art to have modified the methods for producing recombinant AAV particles as taught by Lee and have obtained at least about 1 x 1015 viral genomes as taught by Yu because both Lee and Yu disclose similar methods for obtaining rAAV particles with AAV production enhancers, as discussed above. Further, Yu discloses the rAAV particles comprises up to about 2 x 1011 of viral genomes per milliliter (mg/ml)(see e.g. abstract, para. 6-10, 44, 110, claims 25, and 50-51). Thus, a person of ordinary skill in the art would have had predictable results with a reasonable expectation of success because both Lee and Yu teach that incorporating AAV production enhancers increasing the yield of rAAV particles, which were taught in methods known to a person of ordinary skill in art.
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Response to Traversal:
Applicant argues that the prior art of Yu mentions DMSO once in the entire document, and that DMSO is mentioned in combination with nocodazole (Remarks, page 4). Applicant argues that a person of ordinary skill in the art would have known that nocodazole enhances rAAV production due to its activity of arresting the cell cycle (see Schaffer et al., WO2021/221956, attached as Appendix A). Applicant argues that Yu’s single mention of “nocodazole-DMSO” would have had a meaningful effect on rAAV production (remarks, page 5).
Applicant arguments are acknowledged, have been fully considered, and have been deemed unpersuasive.
In response to Applicants argument that DMSO is only mentioned once (see para. 12 of Yu), it is noted that the preferred embodiments are not the only teaching of a reference. “The use of patents as references is not limited to what the patentees describe as their own inventions or to the problems with which they are concerned. They are part of the literature of the art, relevant for all they contain.” In re Heck, 699 F.2d 1331, 1332-33, 216 USPQ 1038, 1039 (Fed. Cir. 1983) (quoting In re Lemelson, 397 F.2d 1006, 1009, 158 USPQ 275, 277 (CCPA 1968)). A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill the art, including nonpreferred embodiments. Merck & Co. v. Biocraft Laboratories, 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989). Further, it is noted that the MPEP 2123 (I) states that patents are relevant as prior art for all they contain, and that a reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill the art, including nonpreferred embodiments.
In the instant case, the citations of Yu are cited as “see for example”(e.g.) and the disclosures are referencing parts of Yu that discloses using an AAV-enhancer. As discussed above, Yu discloses that an AAV-enhancer may be nocodazole-DMSO (see para. 12). It is noted in the Examples of Yu, that Yu does not teach the identity of the AAV-enhancer. Therefore, it is reasonable that a person of ordinary skill in the art would be able use any AAV-enhancer listed in Yu (e.g. para. 12), and that AAV-enhancer would be used in the instant method of Yu (see e.g. Examples 1, 3, and 7). In response to Applicants argument regarding Yu disclosing nocodazole-DMSO, it is noted that claims read on “comprising” (see MPEP 2111.03). In the instant case, the claims do not exclude other embodiments, such as the addition of nocodazole-DMSO. As discussed above, Yu discloses that the rAAV particles comprises up to about 2 x 1011 of viral genomes per milliliter (mg/ml)(see e.g. abstract, para. 6-10, 44, 110, claims 25, and 50-51). Thus, it is unclear how a person of ordinary skill in the art would not have known that an AAV-enhancer would have a meaningful effect on rAAV production since Yu discloses that incorporating AAV production enhancers provides maximal AAV production, where the rAAV particles comprise up to about 2x1011 viral genomes per milliliter (vg/mL)(see e.g. abstract and para. 6).
In response to Applicants assertion that Schaffer et al., WO2021/221956 (see Appendix A) teaches the effects of cell cycle blocking agents, such as nocodazole on AAV production (Remarks, page 5). It is unclear what “effects” that Applicant is referring too because Schaffer discloses cell cycle blocking agents, such as nocodazole, DMSO, and sodium butyrate (see Schaffer, para. 63). It is noted that nocodazole enhances rAAV production due to its activity of arresting the cell cycle. Contrary to Applicants belief that this not a meaningful effect on rAAV production, the prior art of Schaffer also discloses a first culture medium without a cell cycle blocking agent (i.e. AAV enhancer like nocodazole or DMSO) and then discloses a second culture medium with a cell cycle blocking agent (i.e. AAV enhancer like nocodazole or DMSO)(see para. 52 of Schaffer, reproduced below). Further[AltContent: textbox ([img-media_image1.png])], it is noted that Schaffer discloses that DMSO is a suitable agent that blocks the G1 cell cycle phase (para. 63). Therefore, a person of ordinary skill in the art would know to add the cell cycle blocking agent like DMSO in the second medium as taught by Schaffer and not add the cell cycle blocking agent in a first cell culture medium. As discussed above in the new anticipation rejection Schaffer reads on the instant claims.
Applicant argues that there is no motivation for a person of ordinary skill in the art combine the prior art of Yu teaching sodium butyrate and the prior art of Lee with DMSO (Remarks, page 7).
Applicant arguments are acknowledged, have been fully considered, and have been deemed unpersuasive.
In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In the instant case, it would have been obvious for a person of ordinary skill in the art to substitute one known AAV production enhancer (i.e. sodium butyrate) as taught by Lee for another a AAV production enhancer (i.e. DMSO) as taught by Yu, which would have led to predictable results with a reasonable expectation of success because both Lee and Yu teach methods for increasing the yield of rAAV particles (see e.g. abstracts, respectively). In view of the foregoing, when all of the evidence is considered, the totality of the rebuttal evidence of nonobviousness fails to outweigh the evidence of obviousness.
Applicant argues that the prior art of Lynch teaches away from because Lynch discloses that low DMSO concentration (5% or less) are ineffective (Remarks, page 7).
Applicant arguments are acknowledged, have been fully considered, and have been deemed unpersuasive.
In response to Applicants argument that Lynch teaches away, it is noted that preferred embodiments are not the only teaching of a reference. “The use of patents as references is not limited to what the patentees describe as their own inventions or to the problems with which they are concerned. They are part of the literature of the art, relevant for all they contain.” In re Heck, 699 F.2d 1331, 1332-33, 216 USPQ 1038, 1039 (Fed. Cir. 1983) (quoting In re Lemelson, 397 F.2d 1006, 1009, 158 USPQ 275, 277 (CCPA 1968)). A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill the art, including nonpreferred embodiments. Merck & Co. v. Biocraft Laboratories, 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989).
Contrary to Applicants assertion Lynch does not explicitly state that concentrations of 5% or less of DMSO are ineffective. Lynch explicitly discloses that 10% DMSO was optimal and tests a range of DMSO from 5% to 20% (see Lynch fig. 1-2), but does not state 5% of DMSO is ineffective. As discussed above, Lynch discloses that protein expression yield in human embryonic kidney cells (i.e. HEK293) could be enhanced with a brief treatment of dimethyl sulfoxide (DMSO) solution (see e.g. title and abstract). Further, Lynch it is noted that the method of Lynch only treated with 10% DMSO for five minutes (see page 9). Lynch discloses treating mammalian (i.e. HEK293) cells with dimethyl sulfoxide (DMSO) solution at 5% (v/v)(see e.g. Fig. 2, page 6). As discussed above, a person of ordinary skill could have substituted one AAV production enhancer for another with predictable results and a reasonable expectation of success, since Lee, Yu, and Lynch disclose methods involving mammalian HEK293 cells and DMSO, which are readily available and deliverable using similar techniques.
In view of the foregoing, when all of the evidence is considered, the totality of the rebuttal evidence of nonobviousness fails to outweigh the evidence of obviousness.
Conclusion
No claim is allowed.
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JOSEPHINE GONZALES
Examiner
Art Unit 1631
/JOSEPHINE GONZALES/ Examiner, Art Unit 1631
/JAMES D SCHULTZ/ Supervisory Patent Examiner, Art Unit 1631
Prosecution Insights