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 .
Amendments
In the reply filed 11/21/2025, Applicant has amended Claim 48.
Claims 48-49, 51, 53-64 are under consideration.
Priority
This application is a Divisional of 14/914,528 filed 2/25/2016, now US Patent 10,883116, which was a 371 of PCT/IB2014/064127 filed on 8/28/2014, which claimed benefit to the foreign application UK 1315321.8 filed 8/28/2013.
As stated in the prior Office action, foreign application UK 1315321.8 filed 8/28/2013 does not provide support for a Cas9 protein. Claims 61 & 62 are being given the filing date of PCT/IB2014/064127 filed on 8/28/2014.
Withdrawn 35 USC § 102
The prior rejection of Claim 48, 56-60, and 63-64 under 35 U.S.C. 102(a)(1) as being anticipated by Vuillar et al. (Biochem J, 1995, 305:337-343) is withdrawn in light of Applicant’s amendment of Claim 48 to no longer recite NDSB-211 (compound 02), as the transduction compound.
The prior rejection of Claims 48, 49, 53, 56-60, and 63-64 under 35 U.S.C. 102(a)(1) as being anticipated by Yun et al. (Cancer Cell, 2007, 11:217-227) is withdrawn in light of Applicant’s amendment of Claim 48 to no longer recite NDSB-211 (compound 02), as the transduction compound.
Withdrawn 35 USC § 103
The prior rejection of Claims 54-55 under 35 U.S.C. 103 as being unpatentable over Yun et al. (Cancer Cell, 2007, 11:217-227), in view of Sirinupong et al. (JBC, 2010, 285:40635-40644) and Sousa et al. (Meth Enzym, 1997, 276:131-143)
is withdrawn in light of Applicant’s amendment of Claim 48 to no longer recite NDSB-211 as the transduction compound.
The prior rejection of Claims 48-49, 53, 56-59, and 63-64 under 35 U.S.C. 103 as being unpatentable over Pepperberg et al. (US 2008/0293915, prior art of record), in view of Yun et al. (Cancer Cell, 2007, 11:217-227) is withdrawn in light of Applicant’s amendment of Claim 48 to no longer recite NDSB-211 as the transduction compound.
The prior rejection of Claim 51 under 35 U.S.C. 103 as being unpatentable over Pepperberg et al. (US 2008/0293915, prior art of record), in view of in view of Yun et al. (Cancer Cell, 2007, 11:217-227), as applied to claim 48, in further view of Hassell et al., (Acta Crystal, 2007, D63:72-79:1818-1826, prior art of record) is withdrawn in light of Applicant’s amendment of Claim 48 to no longer recite NDSB-211 as the transduction compound.
The prior rejection of Claims 61 and 62 under 35 U.S.C. 103 as being unpatentable over Zhang et al. (WO2015/089364, filed 12/12/2014, with priority to US provisional 61/915,251 filed 12/12/2013), in view of Yun et al. (Cancer Cell, 2007, 11:217-227) is withdrawn in light of Applicant’s amendment of Claim 48 to no longer recite NDSB-211 as the transduction compound.
New 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim 48-49, 56, 59-60, and 63-64 are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by Vick et al. (US 2002/0052026, filed 10/08/1997, published 5/02/2002)
In regard to claim 48, Vick teaches and claims a protein refolding buffer comprising:
[AltContent: textbox ([img-media_image1.png])]N-methyl-N-piperidine propane sulfonic acid, alias 1-methyl-1-sulfonylpropyl-piperidine (i.e., NDSB-221, compound 3 of Table 1), (see from [0039] adjacent),
50 mM Tris (about pH 8.5),
5 mM EDTA,
Glutathione,
1.0 M NaCl,
and a recombinant TGF-beta protein (e.g., BMP protein) (see all working Examples for buffer constituents and Claims 1-4, 6 and 7 of Vick for NDSBs).
With respect to preamble of claim 48, Vick is silent to the use of said invention as a “transduction buffer for transducing a protein into a cell”, which is an intended use of the claimed composition, yet it meets all of the claimed structural limitations. Furthermore, Applicant’s specification evidences that the claimed transduction buffers comprise osmolarities of more than 1000 mOsm/kg (p. 21, last two para. to p.22, last para, p. 23, 1st & 3rd para.) can be used for transduction (pgs. 28-30). Thus, absent evidence to the contrary, the crystallization buffer of Vick is capable of being used as a transduction buffer.
Furthermore, it is noted that the use of a product for a particular purpose is not afforded patentable weight in a product claim where the body of the claim does not depend on the preamble for completeness but, instead, the structural limitations are able to stand alone. The MPEP states that,”.. in apparatus, article, and composition claims, intended use must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art.” In re Casey, 152 USPQ 235 (CCPA 1967); In re Otto , 136 USPQ 458, 459 (CCPA 1963)(MPEP 2111.02).
In regard to claim 49, as stated supra, Vick teaches the salt is sodium chloride.
In regard to claim 56, as stated supra, Vick teaches the pH buffer is Tris.
In regard to claim 59, as stated supra, Vick teaches the presence of a protein of interest.
In regard to claim 60, as stated supra, Vick teaches the protein of interest is bone morphogenetic protein that induces bone or cartilage formation by signaling to the nucleus and modifying gene expression [0002].
In regard to claims 63 and 64, Vick teaches the commercial grade chemicals under standard laboratory conditions to produce commercial quantities of the protein of interest [0011-0012], therefore this buffer would be reasonably considered as a pharmaceutical composition.
Accordingly, Vick anticipates instant claims.
RESPONSE TO ARGUMENTS
Applicant's arguments filed on 11/21/2025 have been fully considered and they are found persuasive. However, as necessitated by amendment, the prior art teaches a transduction buffer comprising the transduction compound NDSB-221 (compound 3 of Table 1).
Claim 48, 56-59, and 63-64 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kubiak et al. (JBC, 2013, 208:31,22493-22505, published on-line 6/16/2013)
In regard to claim 48, Kubiak et al. teaches a crystallization buffer comprising:
0.28 M NDSB-221 (compound 3 of Table 1)
1.6 M sodium citrate, pH 6.5 (p. 22494, Crystal Structure Determination).
With respect to preamble of claim 48, Kubiak is silent to the use of said invention as a “transduction buffer for transducing a protein into a cell”, which is an intended use of the claimed composition, yet it meets all of the claimed structural limitations. Furthermore, Applicant’s specification evidences that the claimed transduction buffers comprise osmolarities of more than 1000 mOsm/kg (p. 21, last two para. to p.22, last para, p. 23, 1st & 3rd para.) can be used for transduction (pgs. 28-30). Thus, absent evidence to the contrary, the crystallization buffer of Kubiak is capable of being used as a transduction buffer.
Furthermore, it is noted that the use of a product for a particular purpose is not afforded patentable weight in a product claim where the body of the claim does not depend on the preamble for completeness but, instead, the structural limitations are able to stand alone. The MPEP states that,”.. in apparatus, article, and composition claims, intended use must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art.” In re Casey, 152 USPQ 235 (CCPA 1967); In re Otto , 136 USPQ 458, 459 (CCPA 1963)(MPEP 2111.02).
In regard to claim 56, as stated supra, Kubiak teaches the pH buffer Na citrate.
In regard to claims 57-58, as stated supra, Kubiack teaches 0.28 M NDSB-221, in the undiluted form, which is between about 200 nM and about 400 mM. Note that Applicant’s specification states that “about” means “for example, x+10%”, but provides no special definition for the term and therefore the Examiner has interpreted “about” as encompassing an order of magnitude. This is considered a reasonable interpretation of the term “about” based on numerous patent documents that specifically define “about” as encompassing an order of magnitude.
In regard to claim 59, Kubiak teaches the undiluted buffer is mixed 1:1 with the (BACCR)NAT3 protein of interest in 25 mM Tris-HCl pH 7.5. It must be noted that the diluted buffer with the protein of interest still has 0.8 M Na citrate and 0.14 M NDSB-221.
In regard to claims 63 and 64, Kubiak teaches the buffer comprises Milli-Q water and with analytical grade chemicals under standard laboratory conditions, therefore this buffer would be reasonably considered as a pharmaceutical composition.
Accordingly, Kubiak anticipates instant claims.
RESPONSE TO ARGUMENTS
Applicant's arguments filed on 11/21/2025 have been fully considered and they are found persuasive. However, as necessitated by amendment, the prior art teaches a transduction buffer comprising the transduction compound NDSB-221 (compound 3 of Table 1).
New 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claims 53-55 are rejected under 35 U.S.C. 103 as being unpatentable over Kubiak et al. (JBC, 2013, 208:31,22493-22505, published on-line 6/16/2013), in view of Sirinupong et al. (JBC, 2010, 285:40635-40644, prior art of record) and Sousa et al. (Meth Enzym, 1997, 276:131-143, prior art of record)
As stated supra, Kubiak teaches a protein crystallization buffer comprising NDSB and buffers.
However, Kubiak is silent to including glycerol.
In regard to claims 53-55, Sirinugpong teaches a protein crystallization buffer comprising NDSB, PEG, 2.5% glycerol, and buffers (p. 40636, Experimental Procedures, 2nd para.). Note that in regard to claim 55, 2.5% glycerol is about 270 mM.
Accordingly, it would have been obvious to prepare a composition comprising a crystallization buffer comprising NDSB-221 and buffers, and combine about 2.5% glycerol as taught by Sirinugpong with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so as taught by Sousa et al. (1997), who teaches that glycerol was well-known as an additive for crystallization buffers because glycerol has long been used as a structure-stabilizing agent (p. 133, last para.).
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
RESPONSE TO ARGUMENTS
Applicant's arguments filed on 11/21/2025 are acknowledged and have been addressed above.
Claims 48, 56-59, and 63-64 are rejected under 35 U.S.C. 103 as being unpatentable over Pepperberg et al. (US 2008/0293915, prior art of record), in view of Kubiak et al. (JBC, 2013, 208:31,22493-22505, published on-line 6/16/2013)
GABA receptor Embodiment
With respect to claim 48, Pepperberg teaches buffers for the crystallization of the extracellular domain of a GABAC receptor [0021-0022, 0085].
However, although Pepperberg teaches the crystallization buffer is from Hampton Research [0085], they are silent with respect to an NSDB-221 based crystallization buffer.
In regard to claim 48, Kubiak et al. teaches a crystallization buffer from Hampton Research comprising:
0.28 M NDSB-221 (compound 3 of Table 1)
1.6 M sodium citrate, pH 6.5 (p. 22494, Crystal Structure Determination).
Accordingly, it would have been obvious to prepare a composition comprising the extracellular domain of a GABA receptor for crystallization in a Hampton Research based crystallization buffer as taught by Pepperberg, and choose the Hampton Research crystallization buffer of Kubiak with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so as taught by Kubiak because this Hampton Research crystallization buffer allowed them to be one of the first to crystallize the structure at a 2.14 A resolution (p. 22499, last para.).
With respect to preamble of claim 48, Pepperberg and Kubiak are silent to the use of said invention as a “transduction buffer for transducing a protein into a cell”, which is an intended use of the claimed composition, yet it meets all of the claimed structural limitations.
Furthermore, it is noted that the use of a product for a particular purpose is not afforded patentable weight in a product claim where the body of the claim does not depend on the preamble for completeness but, instead, the structural limitations are able to stand alone. The MPEP states that,”.. in apparatus, article, and composition claims, intended use must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art.” In re Casey, 152 USPQ 235 (CCPA 1967); In re Otto , 136 USPQ 458, 459 (CCPA 1963)(MPEP 2111.02).
In regard to claim 56, as stated supra, Kubiak teaches the pH buffer Na citrate.
In regard to claims 57-58, as stated supra, Kubiak teaches 0.28 M NDSB-221, in the undiluted form, which is between about 200 nM and about 400 mM. Note that Applicant’s specification states that “about” means “for example, x+10%”, but provides no special definition for the term and therefore the Examiner has interpreted “about” as encompassing an order of magnitude. This is considered a reasonable interpretation of the term “about” based on numerous patent documents that specifically define “about” as encompassing an order of magnitude.
In regard to claim 59, as stated supra, Pepperberg teaches the crystallization buffer comprises the ligand binding domain of the GABAC receptor.
In regard to claims 63 and 64, Kubiak teaches the buffer comprises Milli-Q water and with analytical grade chemicals under standard laboratory conditions, therefore this buffer would be reasonably considered as a pharmaceutical composition. Furthermore, Pepperberg teaches that standard laboratory techniques are used for preparing the protein compositions in order to avoid contamination [0010, 0109], and thus meet the generic definition of pharmaceutical composition.
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
RESPONSE TO ARGUMENTS
Applicant's arguments filed on 11/21/2025 are acknowledged and have been addressed above.
Claim 51 is rejected under 35 U.S.C. 103 as being unpatentable over Pepperberg et al. (US 2008/0293915, prior art of record), in view of Kubiak et al. (JBC, 2013, 208:31,22493-22505, published on-line 6/16/2013), as applied to claim 48, in further view of Planamente et al. (Mol Microbio, 2012, 86(5)1085-1099)
As discussed previously, Pepperberg and Kubiak suggest a GABAC receptor protein crystallization buffer that can be used to transduce a protein into a cell.
However, Pepperberg and Kubiak are silent with respect to the GABAC receptor protein crystallization buffer further comprising GABA.
With respect to claim 51, Panamente teaches adding 10 mM GABA to a GABA binding protein solution prior to crystallization (p. 1096, 2nd para. of Crystallization and structure determination).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to prepare the GABA receptor protein crystallization buffer as suggested by Pepperberg and Kubiak and combine GABA as taught by Planamente with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so as taught by Planamente because the co-crystallization of GABA with the GABA binding protein provides structural information about the ligand binding pocket (Abstract, Introduction, 2nd para.). Furthermore, Planamente makes direct comparisons between the GABA binding protein of her work (i.e., Atu4243) and the GABAC receptor with a shared GABA binding model including planar and extended conformation of GABA, the stacking of GABA within aromatic residues, and interaction between the carboxylate of GABA and a common Arg residue (Discussion, 3rd para.), thereby demonstrating a reasonable expectation of success in doing so.
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
RESPONSE TO ARGUMENTS
Applicant's arguments filed on 11/21/2025 are acknowledged.
Applicant argues that there was no reasonable expectation of success in adding a ligand according to Hassell to the GABA binding proteins. Applicant cites Hassell as teaching that the presence of the ligand has the potential to induce significant conformational changes to the protein and may require additional screen. In addition, Applicant argues that the addition of a ligand to the crystallization buffer is only one of four possible pathways for the addition of the ligand to generate protein-ligand crystals the including a ligand in the crystallization buffer can be unpredictably and can lead to the cracking of crystals.
Applicant’s arguments have been fully considered but are not found persuasive in light of the rejection over Pepperberg, in view of Kubiak and Planamente, who teach that it would have been predictably obvious to include GABA in the protein crystallization buffer to form co-crystals.
Claims 61 and 62 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al. (WO2015/089364, filed 12/12/2014, with priority to US provisional 61/915,251 filed 12/12/2013), in view of Kubiak et al. (JBC, 2013, 208:31,22493-22505, published on-line 6/16/2013)
Cas9 Embodiment
With respect to instant claims, Zhang teaches compositions for the crystallization of Cas9 (Example 8, [00218-00222] of priority document).
However, Zhang is silent with respect to an NSDB-221 based crystallization buffer.
In regard to instant claims, Kubiak et al. teaches a crystallization buffer for a enzymatic protein comprising:
0.28 M NDSB-221 (compound 3 of Table 1)
1.6 M sodium citrate, pH 6.5 (p. 22494, Crystal Structure Determination).
Accordingly, it would have been obvious to prepare a composition comprising the Cas9 enzyme for crystallization as taught by Zhang, and choose the protein enzyme crystallization buffer of Kubiak with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so as taught by Kubiak because this crystallization buffer allowed them to be one of the first to crystallize the structure of an enzymatic protein at a 2.14 A resolution (p. 22499, last para.).
With respect to the intended use of the composition, Zhang and Kubiak are silent to the use of said invention as a “transduction buffer for transducing a protein into a cell”, which is an intended use of the claimed composition, yet it meets all of the claimed structural limitations.
Furthermore, it is noted that the use of a product for a particular purpose is not afforded patentable weight in a product claim where the body of the claim does not depend on the preamble for completeness but, instead, the structural limitations are able to stand alone. The MPEP states that,”.. in apparatus, article, and composition claims, intended use must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art.” In re Casey, 152 USPQ 235 (CCPA 1967); In re Otto , 136 USPQ 458, 459 (CCPA 1963)(MPEP 2111.02).
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
RESPONSE TO ARGUMENTS
Applicant's arguments filed on 11/21/2025 are acknowledged and have been addressed above.
Terminal Disclaimer
The terminal disclaimer filed on 3/03/2025 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of 15/775,791, now US 12,209,252 has been reviewed and was accepted 4/09/2025. The terminal disclaimer has been approved and recorded, and the indication by the Examiner in the prior Office action that the terminal disclaimer was disqualified was in error.
Withdrawn Double Patenting
The prior rejection of Claims 48-49, 51, 53-64 on the grounds of nonstatutory double patenting as being unpatentable over claims 1-16 of US Patent 12,209,252 (Geijsen et al., Patented 1/28/2025) is withdrawn in light of the terminal disclaimer filed.
Maintained Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory obviousness-type double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); and In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the conflicting application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement.
Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b).
Claims 48-49, 51, 53-64 are provisionally rejected on the grounds of nonstatutory double patenting as being unpatentable over claims 1-7, 11, 13, 19, 21, 24-25, and 32 of copending Application No. 18/576,991. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented
The subject matter claimed in the instant application is disclosed in the cited application as follows: the method for transducing a protein into a cell comprising a transduction buffer of cited application makes obvious the transduction buffer of instant application. The claims of the cited application are drawn to the method of using a species of instantly claimed composition. There is no unobvious step in the co-pending process (i.e., contacting a cell), and the co-pending process is the intended use of instantly claimed composition as taught by the specification.
Since the instant application claims are obvious over cited application claims, said claims are not patentably distinct.
RESPONSE TO ARGUMENTS
Applicant's arguments filed on 11/21/2025 are acknowledged and ask that instant provision double patenting rejection be held in abeyance until the indication of allowable subject matter.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the date of this final action.
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ARTHUR S LEONARD whose telephone number is (571)270-3073. The examiner can normally be reached on Mon-Fri 9am-5pm.
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/ARTHUR S LEONARD/Examiner, Art Unit 1631