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 .
Election/Restrictions
Applicant’s election without traverse of Group I in the reply filed on 12/16/2025 is acknowledged.
Claims 3, 125, 128-129, and 152-163 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 12/16/2025.
Species elections to the following were made:
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Regarding claim 40 of the elected invention, it is noted that the elected species of deblock polymer with m=216 and n=86 is not a species recited in this claim. As such, claim 40 is withdrawn from consideration at this time.
Claims 1, 4-5, 7-8, 24, and 59 and the above species elections are under consideration in the present office action.
Claim Rejections - 35 USC § 112
(1) Claim 4 is rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of (i)-(xx) is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: (i) through (xx) are not species of any common group with a single structural similarity” but rather a list of narrowing embodiment placed in one claim as an alternative limitations. For example (i), (ii), and (iii) define structural/chemical elements of the deblock copolymer, (vii)-(viii) define characteristics of the cells, (x) and (xi) define further active steps in the method, (xii)-(xiv) define aspects of the viral vector, etc.. Thus clearly (i)-(xx) are not species of a genus and do not have such a single structural similarly from which a common function flow, as required by Markush groupings.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
(2) Claim 5 is rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of (i)-(xxiv) is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: similar to claim 4, the listed species of (i)-(xxiv) of claim 5 are actually not species of each other but rather further listing of structural different embodiments limiting aspects of the chemical structure of the deblock copolymer (for example i-x), type of cells (for example xi), further substances added in the method (for example xi-xiii), and more. Thus clearly (i)-(xxiv) are not species of a genus and do not have such a single structural similarly from which a common function flow, as required by Markush groupings.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
(3) Claim 7 is rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of (i)-(xv) is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: similar to claim 4, the listed species of (i)-(xv) are actually not species of each other but rather further listing of structural different embodiments limiting aspects of the chemical structure of the deblock copolymer (for example i-vi), nucleic acids (for example vii-viii), transgene (for example ix-x), and more. Thus clearly (i)-(xv) are not species of a genus and do not have such a single structural similarly from which a common function flow, as required by Markush groupings.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
(4) Claim 8 is rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of (i)-(x) is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: similar to claim 4, the listed species of (i)-(x) are actually not species of each other but rather further listing of structural different embodiments limiting aspects of the chemical structure of the deblock copolymer (for example i-vi), nucleic acids (for example vii and viii), transgenes(for example ix-x), and more. Thus clearly (i)-(x) are not species of a genus and do not have such a single structural similarly from which a common function flow, as required by Markush groupings.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
(5) Claim 24 is rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of (i)-(viii) is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: similar to claim 4, the listed species of (i)-(viii) are actually not species of each other but rather further listing of structural different embodiments limiting aspects of the chemical structure of the deblock copolymer (for example i-iv), nucleic acids (for example vi), transgenes(for example vii), and more. Thus clearly (i)-(viii) are not species of a genus and do not have such a single structural similarly from which a common function flow, as required by Markush groupings.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
It is noted that all of these claims are subject to the species election. As such, a search of the elected species search for the recited limitations as they apply to these species.
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(s) 1, 4-5, 7-8, 24, and 59 is/are rejected under 35 U.S.C. 102(a)(b) as being anticipated by Katz (WO 2003/032915 pub date:4/24/2003; effectively filed 10/16/2001).
Regarding claim 1, Katz discloses contacting Hep-2 cells (i.e. eukaryotic cells) with HSV-1(KOS)gL89 (i.e. a viral vector). HSV-1(KOS)gL89 comprises a nucleic acid encoding a LacZ gene under control of the CMV promoter, beta-galactosidase is expressed after entry of the viral genome into the Hep-2 cells (i.e. a viral vector encoding transgene; a method of (i) transducing a eukaryotic cell to express a transgene or (ii) expressing a transgene in a eukaryotic). N-docosanol suspended in Tetronic 908 or Tetronic 908 vehicle control are also contacted to the Hep-2 cell with the HSV-1(KOS)gL89. Tetronic 908 is a deblock or polyamine comprising PEO subunits and PPO subunits as claimed. Katz further discloses, “The vehicle, Tetronic 908, without n-docosanol, was not inhibitory to viral entry. In fact, treatment of cells with equal volumes of vehicle enhanced the blue color development as much as 40%” meaning that cells are being effectively transduced by the viral vector and the transgene is effectively being express. Further, the presence of Tetronic 908 enhances expression of the transgene as much as 40% (p. 51, line 7 to 25). As such, Katz expressly discloses all of the limitations of claim 1.
Regarding claims 4-5, and 7-8,Tetronic 908 comprises the chemical structure of formula recited in these claims (i)+ in each of the claims. Katz does not disclose all of the recited limitations of the claims; however, they are recited in the alternative with (i)+. Since the limitations of (i)+ have been disclosed the requisite limitations of the claims have been disclose.
Regarding claim 59, this claim specifies limitations of the one of the alternatives of claim 24(vi). The claim does not specify that claim 24 is limited to (vi) specifically. As such, this recitation also is only limiting one of the cited alternatives. As discussed above Tetronic 908 discloses the limitations of the structure of 24(i)+. So the requisite limitations of claim 59 have been met by this disclosure by Katz.
Claim Rejections - 35 USC § 112
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 1, 4-5, 7-8, 24, and 59 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.
When determining if a recited genus has adequate written description, the following is considered:
(1) the broadest reasonable interpretation of the genus is determined;
(2) the disclosure is examined to determine if the specification has provided a representative number of species to describe the complete structure of the genus;
(3) the disclosure is examined to determine whether a representative number of species have been sufficiently described by other relevant characteristics, specified features and functional attributes that would distinguish different members of the claimed genus; and
(4) the state of the art is examined to the determine if it supports/supplement the genus description in the specification in a manner that would demonstrate the application was in possession of the claimed genus at the time of effectively filing.
Broadest Reasonable Interpretation: Independent claim 1 is a highly generic claim overall. Claim 1 recites, the genus “a diblock copolymer comprising polyoxyethylene (PEO) subunits and poleoxypropylene (PPO) subunit”. The breadth of the diblock copolymer comprises a copolymer with any number of PEO subunit and any number of PPO subunits. The copolymer is “comprising” as such any other structural elements can be added onto the ends of the copolymer and/or in between the subunits. As such the genus of diblock polymers is extremely large with a wide variety structure. The claim recites that the diblock copolymer function results in “transducing eukaryotic cell to express a transgene” and this is in conjunction with any viral vector. As such, the claims sets forth a genus of diblock copolymers with large and heterogenous group of species that has the function of impacting transduction of any eukaryotic cell by any viral vector.
Claim 4 narrows the claimed diblock copolymer by reciting:
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Even though the copolymer limits the structure to adding chemical substituents to the end of the diblocker copolymer and a linker of any structure between the PEO and PPO subunits of any number. The chemical substituents and the linker are optional make the broadest scope being that of base claim 1.
Claim 5 narrows the claimed diblock copolymer by reciting:
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This chemical structure limits the claimed structure to not include a linker because the end chemical substituents are optional. The breadth still is quite large with any number of PEO and PPO subunits and any additional chemical structures at the ends.
It is noted that these chemical structures are optional because in all the dependent claims they are recited in alternative with limitations that do no narrow the limitations of the structure but rather the cell, viral vector, transgene, or other agent/further method step. As such, the breadth of the claimed diblock copolymer is as broad as the interpretation for base claim 1.
Description by the Specification:
The specification describes, “The composition and methods of the disclosure are based, in part, on the discovery that diblock copolymers that include a hydrophilic component (e.g., PEO subunits) and a hydrophobic component (e.g., PPO subunits) are capable of promoting viral transduction when contacted with a target cell. These diblock polymers may be used to effectuate transduction of a target cell, while still maintaining robust genetic modification” (p. 1, line 40 to p. 3, line 3 of originally filed specification).
The specification further describes the synthesis of six species of diblock copolymer species, designated DBP1-6. Peripheral mobilized blood CD34.sup.+ stem cells were transduced with lentiviral vector, (Vector only, multiplicity of infection (MOI) 10-20), in the presence of diblock polymers compounds (DBP1-6). The effect of DBP compounds on cell viability (determined 1 day post-transduction; FIG. 1) and transduction efficiency (expressed as fold change in percentage of transduced cells induced by the addition of DBP, relative to cells treated with vector alone; FIGS. 2A-2F) was determined at 12-14 days post transduction. The effect of DBP on integrated vector copy number per cell (VCN) was determined by droplet digital PCR detection of integrated transgene sequences in genomic DNA harvested from cell cultures 12 days post-transduction (FIG. 3). Percentage of transduced cells was assessed by flow cytometry detection of transgene expression (FIG. 4). The effect of DBP compounds in combination with various transduction enhancer elements on cell viability (FIG. 5) and transduction efficiency (FIG. 6) was determined. Notably, diblock copolymers were found to effectuate increases in transduction efficiency of CD34.sup.+ stem cells across a range of PEO and PPO compositions (FIGS. 7 and 8). Diblock copolymers were also found to be compatible with RetroNectin (FIG. 9). Surprisingly, diblock copolymers were also found to engender improvements in transduction efficiency relative to triblock copolymers, particularly poloxamer 338 (FIG. 10). See page 143, Example 2 of the specification.
As such, the specification describes a vastly smaller number of diblock copolymer species (6 species) that have been shown improve lentiviral transduction of HSCs. A vast number of species that have the relevant and requisite function of imparting any viral vector transduction remains undescribed by the specification. As such, the specification fails to provide adequate written described of a representative number of species to sufficiently describe the complete structure of the large and heterogenous genus of diblock copolymer that facilitate and enhance viral transduction of cells.
State of Art: A search of art at and before the time of effective filing does not provide many examples of diblock copolymers comprising PEO subunit and PPO subunits have a corresponding function associated with viral vector transduction in eukaryotic cells as claimed. Kim et al (2018; HHS Public Access, Author manuscript available in PMC 7/10/2018 and published as final edit in Biomacromolecules 18(7):2090-2101. See pp. 1-26 Author Manuscripts) reports PEO-PPO co-polymers have a variety of functions with Kim et al focusing PEO-PPO copolymer function in protection of cellular membranes from various stress. Kim et al reports that PEO-PPO triblock polymers have been demonstrated to be protective. Though numerous block copolymers exist, evaluation of alternative architecture, composition, and size has been minimal. Kim et al describes Comparative evaluation of a systematic set of PEO-PPO diblock and PEO-PPO-PEO triblock copolymers demonstrates that the diblock architecture can be protective in vitro. Short PPO blocks hinder protection with >9 PPO units needed for protection at 150 µM and >16 units needed at 14 µM. Addition of a tert-butyl end group enhances protection at reduced concentration. When the end group and PPO length are fixed, increasing the PEO length improves protection. See page 1, abstract. Kim et al more specifically reports significant membrane protection to isotonic recovery is only observed with a hydrophobic segment of at least 16 PPO monomer units as well as a tert-butyl end group. Without tert-butyl, greater than 16 units of PPO were needed with around 32 PPO monomer units being sufficient. With sufficient hydrophopic segment, increasing protection efficacy was observed with increasing PEO length. Overall, we have found that hydrophobicity controlled by PPO length and end group is a critical factor to determine membrane protection efficacy, in addition to the PEO length. See page 10.
Thus, Kim et al. demonstrates that the number of PEO and PPO subunits, their ratio, the diblock length and overall architecture significantly impact their ability to function as a cell membrane protectant. Therefore, not any and all chemical configurations of a diblock copolymers comprising PEO and PPO subunit will predictably have a desired function.
Uchida et al (Molecular Therapy: Methods & Clinical Development 2019 Vol1 13; of record in IDS 6/10/2022) provides description of transduction of HSC with lentiviral vectors encoding transgenes is enhances by coadministration of PEO-PPO triblock copolymers (see abstract). However, Uchida does not describe the part of the triblock copolymer needed to impart its function in viral transduction. Further, it does not describe any common elements that would be need by a PEO-PPO diblock copolymer that impart the same function in viral transduction to PEO-PPO diblock copolymer. As such, the art does not provide sufficient description of a representative number of PEO-PPO diblock copolymers or relevant structural part of such a diblock copolymer needs to impart the described function in viral transduction in the art and this application’s disclosure. As such, the art does not supplement the description not provided by the specification in the instant application.
In conclusion, the breadth of the claimed genus of diblock copolymer comprising PEO and PPO subunits with the requisite associated function in viral vector transduction does not have adequate written description. While the specification does describe many species variant of diblock copolymers comprising PEO and PPO subunit showing the heterologous and vastly large number of species in the genus, the specification only sufficiently describes six species of the diblocker copolymer that have the requisite function in lentiviral vector transduction in HSC. Further, while the disclosure list a number of possible chemical structures contemplated in the application, it is still a portion of this vast heterogenous genus and also does not describe the most relevant structural characteristics that impart the function in viral vector transduction and transgene expression. A review of the art also does not provide such disclosures to supplement the shortcomings of the disclosure in the instant application. Further, the art teaches that not any and all configuration of a diblock copolymer will predictably impart a desired function. As such, outside of the 6 species described by the application with not description of the structurally relevant traits of the diblock copolymer genus, one of skill in the art could not envision the diblock copolymer structures with the requisite function in viral vector transfection that describe the complete structure of the claimed genus. As such, one would have envision that the application was in possession of the claimed diblock copolymer comprising PEO and PPO subunits with the requisite function in viral vector transduction and transgene expression at the time of effectively filing the claimed invention.
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARCIA STEPHENS NOBLE whose telephone number is (571)272-5545. The examiner can normally be reached M-F 9-5:30.
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MARCIA S. NOBLE
Primary Examiner
Art Unit 1632
/MARCIA S NOBLE/ Primary Examiner, Art Unit 1632
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