DETAILED ACTION
Status of the Application
Claims 5, 7-11, 14-15, 21-22, 33, 35-41, 43-44, 48-50, 52-58 are pending.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant’s amendment of claims 5, 15, 21, 33, 36-41, 43, and addition of claims 52-58 as submitted in a communication filed on 12/15/2025 is acknowledged.
A request for continued examination under 37 CFR 1.114 was filed in this application after a decision by the Patent Trial and Appeal Board, but before the filing of a Notice of Appeal to the Court of Appeals for the Federal Circuit or the commencement of a civil action. 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examination under 37 CFR 1.114 and the fee set forth in 37 CFR 1.17(e) has been timely paid, the appeal has been withdrawn pursuant to 37 CFR 1.114 and prosecution in this application has been reopened pursuant to 37 CFR 1.114. Applicant’s submission filed on 12/15/2025 has been entered.
New claims 52-58 are directed to the elected subject matter. Claims 21-22, 35-40 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 11/6/2019. Claims 5, 7-11, 14-15, 33, 41, 43-44, 48-50, 52-58 are at issue and are being examined herein.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim Objections
Claims 5, 15, 43, and 52 are objected to due to the recitation of “si RNA”. As known in the art and also indicated in the specification, the term should be “siRNA”. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b) or Second Paragraph (pre-AIA )
Claims 5, 7-11, 41, 57-58 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention. New grounds of rejection are necessitated by amendment.
Claim 5 (claims 7-11, 41, 57-58 dependent thereon) is indefinite in the recitation of “…wherein .. a vector comprising the at least one second polynucleotide encodes at least one product of interest and comprises at least one second regulatory sequence” for the following reasons. As written, it is unclear if the limitation “encodes at least one product of interest and comprises at least one second regulatory sequence” refers to the vector or the second polynucleotide. If the limitation refers to the second polynucleotide, the claims should be amended to recite “wherein….(ii) a vector comprises the at least one second polynucleotide, wherein the at least second polynucleotide encodes at least one product of interest and comprises at least one second regulatory sequence”. Correction is required.
Claim 33 is indefinite in the recitation of “wherein the product of interest is the protein heterologous to the recombinant eukaryotic cell and the protein is a therapeutic protein” for the following reasons. Claim 15, from which claim 33 depends, already refers to a product of interest which is a therapeutic protein heterologous to the recombinant eukaryotic cell. Since claim 15 already limits the genus of proteins to therapeutic proteins, it is unclear as to how the recitation of “and the protein is a therapeutic protein” further limits the claim. If the intended limitation is “wherein the product of interest is the therapeutic protein heterologous to the recombinant eukaryotic cell”, the claim should be amended accordingly. Correction is required.
Claims 54-55 are indefinite in the recitation of “wherein the polypeptide is a polypeptide corresponding to SEQ ID NO: 28” for the following reasons. The term “corresponding to SEQ ID NO: 28” can be interpreted as "sequence analogous to or comparable to SEQ ID NO: 28”. Thus, it is unclear as to whether or not the term "sequence corresponding to SEQ ID NO: 28” limits the recited protein to a protein that has SEQ ID NO: 28. If the polypeptide is not limited to a polypeptide that has SEQ ID NO: 28, then the scope of claims 54-55 would be broader than that of the claims from which they depend, thus not being proper dependent claims. If the intended limitation is “wherein the first polynucleotide encodes the polypeptide of SEQ ID NO: 28”, the claims should be amended accordingly. Correction is required.
Claims 55-56 are indefinite in the recitation of “the eukaryotic expression system of claim 15” for the following reasons. Claim 15 is directed to a recombinant eukaryotic cell and not to a system. For examination purposes, it will be assumed that the claims recite “the recombinant eukaryotic cell of claim 15”. Correction is required.
When amending the claims, applicant is advised to carefully review all examined claims and make the necessary changes to ensure proper antecedent basis and dependency.
Claim Rejections - 35 USC § 112(a) or First Paragraph (pre-AIA )
Claims 5, 7-11, 14-15, 33, 41, 43-44, 48-50 remain rejected and new claims 52-55, 57 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. This rejection as it relates to new claims 52-55, 57 is necessitated by amendment.
This rejection has been discussed at length in prior Office actions and the Examiner’s answer of 8/9/2024. It is maintained and further applied to new claims 52-55, 57 for the reasons of record and those set forth below.
Applicant argues that the claims have been amended to increase the sequence identity to 95% and 99%, and to add a functional limitation. Applicant states that the written description requirement is an inverse function of the skill and knowledge in the art. Applicant cites the teachings of Quick et al., U.S. Patent No. 7,740,882 and the Prasad reference as evidence to show that the skill and knowledge in the art is high with regard to sodium-dependent multivitamin transporters.
Applicant’s arguments have been fully considered but not deemed persuasive to overcome the rejection of claims 5, 7-11, 14-15, 33, 41, 43-44, 48-50 or avoid the rejection of claims 52-55, 57. The Examiner acknowledges the amendments made to the claims. However, the Examiner disagrees with Applicant’s contention that the entire scope of the claims is adequately described.
The claims as amended require a genus of polynucleotides encoding a genus of proteins having at least 95%, 98% or 99% sequence identity to the polypeptide of SEQ ID NO: 28, wherein said proteins have sodium-dependent multivitamin transporter (SMVT) activity for vitamin B5 and/or vitamin H, or SMVT activity for any vitamin (new claims 52-54). Therefore, the claims allow the variants of the polypeptide of SEQ ID NO: 28 to have between 7 to 32 modifications (32 = 0.05x636; 7 = 0.01x636; SEQ ID NO: 28 has 636 amino acids). Using the previously provided formula to calculate the total number of variants of a polypeptide having a specific number of amino acid substitutions, N!x19A/(N-A)!/A!, the total number of variants having 95% sequence identity to the polypeptide of SEQ ID NO: 28 that result solely from substitutions is 636!x1932/(636-32)!/32! or 7.34x1094 variants, the total number of variants having 98% sequence identity to the polypeptide of SEQ ID NO: 28 that result solely from substitutions is 636!x1913/(636-13)!/13! or 1.66x1043 variants, while the total number of variants having 99% sequence identity to the polypeptide of SEQ ID NO: 28 that result solely from substitutions is 636!x197/(636-7)!/7! or 7.2x1024 variants. The specification and the prior art fail to provide a structure/function correlation and/or the structural features required in any variant of the polypeptide of SEQ ID NO: 28 having the recited % sequence identity so that one of skill in the art can determine, from an essentially infinite number of structural variants having the recited % sequence identity, which structural variants of the protein of SEQ ID NO: 28 have the desired SMVT activity.
While Applicant argues that the teachings of Quick et al., U.S. Patent No. 7,740,882 and the Prasad reference are evidence to show that the skill and knowledge in the art is high with regard to sodium-dependent multivitamin transporters, it is noted that (i) Prasad et al. simply disclose one rat SMVT and U.S. Patent No. 7,740,882 discloses a human SMVT, and (ii) there is no mention by Prasad et al. or U.S. Patent No. 7,740,882 as to a structure/function correlation or the structural features which are required in any protein to have SMVT activity, let alone the structural features required in a protein having SMVT activity specific for vitamin B5 and/or vitamin H. With regard to Quick et al., it is reiterated herein that while Quick et al. describe the human sodium/multivitamin transporter protein (hSMVT), and its cloning, this reference does not provide a structure/function correlation or the structural features required in any protein or in a variant of the protein of SEQ ID NO: 28 having the recited % sequence identity that can transport any vitamin, vitamin B5 and/or vitamin H.
As previously indicated, the secondary structure/topology of the human SMVT by itself does not provide any information as to those amino acids that are essential for the transport of these vitamins nor does it provide any clue as to those amino acids that can be modified to create a variant with the recited % sequence identity that is still able to transport these vitamins. Moreover, while the prior art, as evidenced by Quick et al., teaches that the human SMVT protein is a member of a larger family of membrane proteins that catalyze the transport of different solutes to the flux of sodium ions across the plasma membrane (solute:sodium symporter (SSS) family), neither the specification nor the prior art, including the reference by Quick et al., teach those structural features in members of the SSS family that are specific for the transport of any vitamin or vitamin B5/vitamin H. The members of the SSS family are specific with regard to the solute they transport so that it is unlikely that every member of the SSS family will transport vitamin B5/vitamin H. Therefore, even if the argument is made that the prior art provides some structural information linking the hSMVT protein with other members of the SSS family, namely the secondary structure of the hSMVT protein and its topology across the membrane, this information does not provide any clue as to those structural features required in any protein as recited that is able to transport any vitamin or vitamin B5/vitamin H. In addition, Quick et al. teach that the bacterial SSS member PanF (the pantothenate transporter) shares only 15% identity and 18% similarity with hSMVT, which are values that are similar to those obtained between hSMVT and PutP, which is another member of the SSS family that is a proline transporter and not a vitamin B5/vitamin H transporter (section 6; Family Ties). Therefore, it is abundantly clear from the teachings of the prior art that sequence identity/similarity cannot be used to determine which proteins will have the same transport specificity as that of the polypeptide of SEQ ID NO: 28. As such, one of skill in the art would require some knowledge or guidance regarding the structural features that must be present in a protein so that it can transport any vitamin, or vitamin B5/vitamin H for one of skill in the art to determine which proteins have the desired transport activity. This information is completely missing from the specification and the prior art. Therefore, contrary to Applicant’s assertions, one cannot reasonably conclude that the claimed invention is adequately described by the teachings of the specification and/or the prior art.
Claims 5, 7-11, 14-15, 33, 41, 43-44, 48-50 remain rejected and new claims 52-55, 57 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for (i) a eukaryotic expression system that comprises a eukaryotic host cell that comprises a first polynucleotide encoding the protein of SEQ ID NO: 28, and a second polynucleotide that encodes a product of interest, wherein said product of interest is heterologous to the eukaryotic host cell and wherein said product of interest is a therapeutic protein, a visualization marker or an siRNA, and (ii) a kit comprising the eukaryotic expression system of (i), does not reasonably provide enablement for (a) an eukaryotic expression system that comprises a eukaryotic host cell that comprises a first polynucleotide encoding a variant of the protein of SEQ ID NO: 28, wherein said variant has sodium-dependent multivitamin transporter activity for any vitamin, vitamin B5 and/or vitamin H, and a second polynucleotide that encodes a product of interest, wherein said product of interest is heterologous to the eukaryotic host cell and wherein said product of interest is a therapeutic protein, a visualization marker or an siRNA, and (b) a kit comprising the eukaryotic expression system of (a). The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims. This rejection as it relates to new claims 52-55, 57 is necessitated by amendment.
This rejection has been discussed at length in prior Office actions and the Examiner’s answer of 8/9/2024. It is maintained and further applied to new claims 52-55, 57 for the reasons of record and those set forth below.
Applicant argues that the claims have been amended to increase the sequence identity to 95% and 99%, and to add a functional limitation. Applicant states that determination of whether any experimentation is undue has to take into account several factors that include but are not limited to the Wands factors. Applicant states that the breadth of the claims has been significantly reduced and that the level of skill in the art is high. Applicant points out that one could perform a sequence alignment with the protein of Prasad et al. Applicant states that one could determine which amino acids might be important to the function of the polypeptide by aligning several sequences of polypeptides having the same function and belong to different species and determine which ones are conserved by finding information from the prior art. Applicant states that the specification refers to sequence alignments and how to perform them. Applicant states that the specification provides working examples and how to test whether different mutations affect the function of the protein being mutated. Applicant states that any experimentation required is merely routine and that the specification provides the required guidance with respect to the direction in which the experimentation should proceed.
Applicant’s arguments have been fully considered but not deemed persuasive to overcome the rejection of claims 5, 7-11, 14-15, 33, 41, 43-44, 48-50 or avoid the rejection of claims 52-55, 57. The Examiner acknowledges the amendments made to the claims and the reduction in scope. However, the Examiner disagrees with Applicant’s contention that the entire scope of the claims is fully enabled.
As indicated above, the claims as amended require a genus of polynucleotides encoding a genus of proteins having at least 95%, 98% or 99% sequence identity to the polypeptide of SEQ ID NO: 28, wherein said proteins have sodium-dependent multivitamin transporter (SMVT) activity for vitamin B5 and/or vitamin H, or SMVT activity for any vitamin (new claims 52-54). The variants of the claims can have between 7 to 32 modifications with respect to the polypeptide of SEQ ID NO: 28. The total number of structural variants having 95% , 98% or 99% sequence identity to the polypeptide of SEQ ID NO: 28 that result solely from substitutions is essentially infinite (95% sequence identity = 7.34x1094 variants, 98% sequence identity = 1.66x1043 variants, and 99% sequence identity = 7.2x1024 variants). See calculations above.
As previously indicated, the specification and the prior art are silent with regard to the structural features required in any variant having the recited % sequence identity so that the variant can have SMVT activity for any vitamin, or SMVT activity specific for vitamin B5 and/or vitamin H. Furthermore, there is no structure/function correlation that would provide those structural features that are required for a variant having the recited % sequence identity to have the required vitamin transport activity.
While Applicant argues that one could perform a sequence alignment with the proteins of different species having the same function and determine which ones are conserved by finding information from the prior art, it is noted that (i) there is no disclosure in the prior art of amino acids that are conserved in proteins that have SMVT activity for any vitamin, or for vitamin B5 and/or vitamin H, and there is no knowledge as to the conserved regions which are specifically associated with SMVT activity for vitamin B5 and/or vitamin H, and (ii) the conserved regions that one could find simply by aligning protein sequences are not necessarily associated with function and are also dependent upon the sequences used in the alignment. These conserved regions can vary depending on the protein sequences used in the alignment. As known in the art, conserved regions in a protein alignment are also a function of how closely related the natural sources of the proteins are. Therefore, unless there is additional information indicating which structural elements are specifically associated with SMVT activity, it would be erroneous to assume that any conserved region one could find aligning any set of proteins having vitamin transport activity is necessarily associated with vitamin transport activity.
While Applicant argues that (i) the specification provides working examples and how to test whether different mutations affect the function of the protein being mutated, and (ii) any experimentation required is merely routine and that the specification provides the required guidance with respect to the direction in which the experimentation should proceed, it is noted that while it is agreed that there are tests to determine if a protein meets the recited functional limitations, the issue in the instant case is whether the amount of information provided by the specification and/or the prior art would allow one of skill in the art to fully enable the full scope of the claims without undue experimentation.
As indicated in prior Office actions, Quick et al. teach that the bacterial SSS member PanF (the pantothenate transporter) shares only 15% identity and 18% similarity with hSMVT, which are values that are similar to those obtained between hSMVT and PutP, which is another member of the SSS family that is a proline transporter and not a vitamin B5/vitamin H transporter (section 6; Family Ties). Therefore, it is evident from the prior art that (a) sequence identity/similarity alone cannot be used to determine which proteins will have the same transport specificity as that of the polypeptide of SEQ ID NO: 28, (b) there is no art recognized structure/function relationship, and (c) the level of one of skill in the art is not high with regard to determining which variants of the polypeptide of SEQ ID NO: 28 have the desired SMVT activity. Since there is no disclosure of a structure/function correlation or structural features required in any SMVT protein or an SMVT protein that transports vitamin B5 and/or vitamin H, one of skill in the art would have to (a) test an essentially infinite number of variants of the polypeptide of SEQ ID NO: 28 that have the recited % sequence identity, and (b) determine which of this infinite number of variants have the ability to transport vitamin B5 and/or vitamin H. Even if the argument is made that one of skill in the art can make the structural variants recited in the claims, and one of skill in the art can use an assay to determine if the variants have the desired activity, testing an essentially infinite number of variants and determining whether they have SMVT activity for vitamin B5 and/or vitamin H is not deemed routine experimentation. Therefore, for the reasons of record and those set forth above, one cannot reasonably conclude that the entire scope of the claims is fully enabled by the teachings of the specification and/or the prior art.
Claim Rejections - 35 USC § 102 (AIA )
Claims 5, 7, 9-11, 14-15, 33, 41, 43, 50 were rejected under 35 U.S.C. 102(a)(1) as being anticipated by Prasad et al. (The Journal of Biological Chemistry 273:7501-7506, 1998) as evidenced by Verardi et al. (Journal of Virology 75(1):11-18, 2001) and Moss (Annual Rev. Biochem. 59:661-688, 1990).
In view of the amendment of claims 5, 15, 41, 43, 50, which now require a polynucleotide encoding a protein having at least 95% sequence identity with the polypeptide of SEQ ID NO: 28, and the fact that the rat sodium-dependent multivitamin transporter of Prasad et al. is 92.1% sequence identical to the polypeptide of SEQ ID NO: 28, this rejection is hereby withdrawn.
Conclusion
No claim is in condition for allowance.
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Any inquiry concerning this communication or earlier communications from the examiner should be directed to DELIA M RAMIREZ, Ph.D., whose telephone number is (571) 272-0938. The examiner can normally be reached on Monday-Friday from 8:30 AM to 5:00 PM. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Robert B. Mondesi, can be reached at (408) 918-7584. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
/DELIA M RAMIREZ/Primary Examiner, Art Unit 1652
DR
January 9, 2026