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 .
Detailed Action
This action is in response to the papers filed March 23, 2026.
Amendments
Applicant's amendments, filed March 23, 2026, is acknowledged. Applicant has cancelled Claims 1-22, 24-33, 35, and 37-40, amended Claim 23, and added new claims, Claims 43-48.
Claims 23, 34, 36, and 41-48 are pending.
Election/Restrictions
Applicant has elected without traverse the invention of Group II, Claim 23, drawn to a genomically modified human B cell, classified in C12N 2510/02.
Prior species election requirement has been rendered moot in light of Applicant’s amendments to the claims necessitating insertion of a nucleotide sequence encoding a heavy or light chain of a defined therapeutic monoclonal antibody into an endogenous heavy or light chain.
Priority
This application is a continuation of application 17/384,228, filed on July 23, 2021, now abandoned,
which is a continuation of application 16/152,273, filed on October 4, 2018, now abandoned,
which is a continuation of PCT/US2017/026011 filed on April 4, 2017.
The Examiner also acknowledges that PCT/US2017/026011 filed on April 4, 2017 is a continuation-in-part of application 15/161,213 filed on May 21, 2016, now abandoned,
which is a continuation-in-part of PCT/US2016/025920 filed on April 4, 2016.
See, for example, the Bib Data Sheet of applications 17/384,228 and 16/152,273.
Applicant’s claim for the benefit of a prior-filed application provisional application 62/142,882 filed on April 3, 2015 under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged.
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994)
The disclosure of the prior-filed applications 62/142,882, PCT/US2016/025920, PCT/US2017/026011, 16/152,273, and 17/384,228 fail to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application.
Applicant’s amendment to the independent claim encompasses an attempt to shift or otherwise change the broader genus of human subject/patient populations whose B cells are to be gene-edited and comprise naturally-occurring viral nucleic acids due to naturally-occurring viral infections to a subgenus of humans in which their B cells do not comprise any exogenous viral nucleic acids, as they have not experienced naturally-occurring viral infections, for which there is no support in the instant specification and/or priority documents.
See further discussion below in the 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, New Matter rejection.
Accordingly, the effective priority date of the instant application is granted as March 4, 2022, the filing date of the instant application.
If applicant believes the earlier applications provide support for this disclosure, applicant should point out such support with particularity by page and line number in the reply to this Action.
Claim Objections
1. The prior objection to Claim 23 is withdrawn in light of Applicant’s amendment to the claim.
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.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
2. Claim(s) 23, 34, 36, and 41-48 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.
Applicant has amended Claim 23 to recite “transplantable population of genome-edited B cells, wherein said cells are not immortalized and lack exogenous viral nucleic acids”.
Either this is an inherent property of (that naturally flows from) the population(s) of genome-edited primary human B cells comprising the claimed genome-edits [structures], or it is not.
The claim denotes that not all populations of the genome-edited, non-immortalized, primary human B cells having the claimed genome-edits [structures] and lacking exogenous viral nucleic acids are “transplantable” [function].
To the extent it is not an inherent property (that naturally flows) from the population of genome-edited primary human B cells having the claimed genome-edits [structures], then something must change. The claim is considered to lack adequate written description for failing to recite the structure(s) that is/are necessary and sufficient to cause the recited functional language.
Without a correlation between structure and function, the claim does little more than define the claimed invention by function. That is not sufficient to satisfy the written description requirement. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406 (“definition by function ... does not suffice to define the genus because it is only an indication of what the gene does, rather than what it is’).
In analyzing whether the written description requirement is met for genus claims, it is first determined whether a representative number of species have been described by their complete structure. To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof. The disclosure of a single species is rarely, if ever, sufficient to describe a broad genus, particularly when the specification fails to describe the features of that genus, even in passing. (see In re Shokal 113USPQ283(CCPA1957); Purdue Pharma L.P. vs Faulding Inc. 56 USPQ2nd 1481 (CAFC 2000).
The court explained that “reading a claim in light of the specification, to thereby interpret limitations explicitly recited in the claim, is a quite different thing from ‘reading limitations of the specification into a claim,’ to thereby narrow the scope of the claim by implicitly adding disclosed limitations which have no express basis in the claim.” The court found that applicant was advocating the latter, i.e., the impermissible importation of subject matter from the specification into the claim.). See also In re Morris, 127 F.3d 1048, 1054-55, 44 USPQ2d 1023, 1027-28 (Fed. Cir. 1997).
The claims fail to recite, and the specification fails to disclose, a first population of genome-edited primary human B cells comprising the claimed genome-edits [structures] which are not “transplantable…”, as opposed to a second population of genome-edited primary human B cells comprising the claimed genome-edits [structures] which are “transplantable…”.
Applicant argues that B cells comprising karyotypic abnormalities are not transplantable. However, the argued “karyotype abnormalities”, whatever vague and however few change(s) it might be, are themselves considered to be an arbitrary and subjective determination, for which there is no support in the specification and/or priority documents.
Applicant’s hypothetical argument, suffers from the fact that nowhere in the instant application, nor the priority documents, is it disclosed that the edited B cell is first screened for its karyotype.
The specification is silent to “karyotype”.
The breadth of the claims allows for the transplantable population as a whole to comprise some arbitrary and subjective number of genome-edited, non-immortalized, primary human B cells lacking exogenous viral nucleic acids yet comprise an unrecited and/or undisclosed undesired karyotypic abnormality.
Applicant attempts, by argument alone, with no support in the specification and/or priority documents, to distinguish:
i) a first population of genome-edited B cells, that, while the population as a whole is determined to be “human transplantable”, still comprises one or more B-cells having an undesired karyotype, as opposed to
ii) a second population of genome-edited B cells, that, as a whole is determined to be “human transplantable”, and does not comprise one or more B-cells having an undesired karyotype.
Nowhere in the instant application, nor the priority documents, are these first and second populations disclosed, let alone the selection of the first population, but not the second population.
The population(s) of the genome-edited, non-immortalized, primary human B cells having the claimed genome-edits and lacking exogenous viral nucleic acids that is/are considered to be “transplantable” or ‘not transplantable’ is an arbitrary and subjective determination.
While Figure 1C illustrates editing the genome of a patient’s B cells (syn. primary human B cells), and transplanting said edited B cells back into the patient (syn. autologous transplantation), the Figure is silent to the presence of any karyotypic abnormality, nor a karyotype screening step prior to transplantation, nor selection step for a first genome-edited B cell subpopulation, and their corresponding karyotypic trait(s) thereof, to the exclusion of a second genome-edited B cell subpopulation, and their corresponding karyotypic trait(s) thereof, prior to transplantation.
While the specification’s working examples disclose using the CRISPR/Cas9 system to edit the genome of primary human B cells, nowhere do any working examples actually administer the thus-edited primary human B cells to a human or non-human animal subject.
Nowhere do any working examples actually disclose performing a karyotype analysis on thus-edited primary human B cell population, to thereby select and/or exclude one or more subpopulations of the thus-edited primary human B cell population based on their karyotype, prior to administering the thus-edited primary human B cells to a human or non-human animal subject.
Thus, for the reasons outlined above, it is concluded that the claims do not meet the requirements for written description under 35 U.S.C. 112, first paragraph.
MPEP 2163 - 35 U.S.C. 112(a) and the first paragraph of pre-AIA 35 U.S.C. 112 require that the “specification shall contain a written description of the invention ....” This requirement is separate and distinct from the enablement requirement. Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1340, 94 USPQ2d 1161, 1167 (Fed. Cir. 2010) (en banc)
Dependent claims are included in the basis of the rejection because they do not correct the primary deficiencies of the independent claim(s).
Response to Arguments
Applicant argues that cells known in the art to be not transplantable have karyotype abnormalities or that are immortalized.
Applicant’s argument(s) has been fully considered, but is not persuasive.
As a first matter, and as discussed in the prior Office Action, instant claims place no requirement on the number of cell divisions before and/or after the genome edit, nor do exclude “karyotype abnormalities”, whatever vague and however few change(s) it might be, per Applicant’s hypothetical argument. Applicant fails to provide objective evidence that the B cells expressing heterologous antibodies of the cite prior art are not “human-transplantable”.
The Examiner previously provided the following references to rebut applicant’s arguments regarding the state of the prior art. Note: these references are not considered a part of the rejection(s) but are solely provided to rebut applicant’s argument(s).
Neron et al (Large-Scale In Vitro Expansion of Polyclonal Human Switched-Memory B Lymphocytes, PLoS ONE 7(12): e51946, 9 pages, doi:10.1371/journal.pone.0051946, December 2012; of record) is considered relevant prior art for having taught the ability to in vitro expand primary human B cells, without immortalization, for as many as 65 days, (e.g. pg 5, col. 1, Results) providing large-scale expansion of the primary human B lymphocytes by almost 10^9-fold (e.g. Abstract; Figure 2A-B). Neron et al taught that the culture conditions could allow the expansion of autologous effector human B lymphocytes to be used in cell-based therapies (e.g. pg 8, col. 2, Conclusion).
Kippen et al (Massive ex Vivo Expansion of Human Natural Regulatory T Cells (Tregs) with Minimal Loss of in Vivo Functional Activity, Science Translational Medicine 3(83): e83ra41, 9 pages, 10.1126/scitranslmed.3001809, available online May 18, 2011; of record) is considered relevant prior art for having taught the ability to in vitro expand primary human Treg cells, without immortalization, by us much as 80-fold, yielding about 2x10^10 cells (e.g. Abstract). Kippen et al taught Treg cells were restimulated and expanded at least 4 times, and the culture conditions efficiently produce an off-the-shelf cellular therapy (Abstract).
Thus, Applicant’s argued concern over the formation of hypothetical karyotypic abnormalities due to additional cell divisions, thereby precluding the B cells from being administered to a patient, is contradicted by the prior art and state of the art in cellular therapeutics developing off-the-shelf, multiply expanded, therapeutic lymphocyte populations for clinical medicine, as they are suitable for transplantation into humans.
As a second matter, Applicant argues that B cells comprising karyotypic abnormalities are not transplantable. However, the argued “karyotype abnormalities”, whatever vague and however many change(s) it might be, are themselves considered to be an arbitrary and subjective determination, for which there is no support in the specification and/or priority documents.
Applicant’s hypothetical argument, suffers from the fact that nowhere in the instant application, nor the priority documents, is it disclosed that each and every edited B cell is first screened for its karyotype.
The specification is silent to “karyotype”.
The breadth of the claims allows for the transplantable population as a whole to comprise some arbitrary and subjective number of genome-edited, non-immortalized primary human B cells lacking exogenous viral nucleic acids yet comprise an undesired karyotypic abnormality.
Applicant attempts, by argument alone, with no support in the specification and/or priority documents, to distinguish:
i) a first population of genome-edited B cells, that, while the population as a whole is determined to be “human transplantable”, still comprises one or more B-cells having an undesired karyotype, as opposed to
ii) a second population of genome-edited B cells, that, as a whole is determined to be “human transplantable”, and does not comprise one or more B-cells having an undesired karyotype.
Nowhere in the instant application, nor the priority documents, are these first and second populations disclosed, let alone the selection of the first population, but not the second population.
While Figure 1C illustrates editing the genome of a patient’s B cells (syn. primary human B cells), and transplanting said edited B cells back into the patient (syn. autologous transplantation), the Figure is silent to the presence or absence of any karyotypic abnormality, nor a karyotype screening step prior to transplantation, nor selection step for a first genome-edited B cell subpopulation, and their corresponding karyotypic trait(s) thereof, to the exclusion of a second genome-edited B cell subpopulation, and their corresponding karyotypic trait(s) thereof, prior to transplantation.
While the specification’s working examples disclose using the CRISPR/Cas9 system to edit the genome of primary human B cells, nowhere do any working examples actually administer the thus-edited primary human B cells to a human or non-human animal subject.
Nowhere do any working examples actually disclose performing a karyotype analysis on thus-edited primary human B cell population, to thereby select and/or exclude one or more subpopulations of the thus-edited primary human B cell population based on their karyotype, prior to administering the thus-edited primary human B cells to a human or non-human animal subject.
New matter
3. Claim(s) 23, 34, 36, and 41-48 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.
Applicant has amended Claim 23, and added new Claim 44, to recite transplantable population of genome-edited B cells, wherein said cells…lack exogenous viral nucleic acids.
Clear support for the new limitation(s) cannot be found in the instant application or priority documents. Accordingly, the amendment(s) to Claim(s) 23 and 44 is/are considered to constitute new matter.
MPEP 2163.06 notes “If new matter is added to the claims, the examiner should reject the claims under 35 U.S.C. 112, first paragraph - written description requirement. In re Rasmussen, 650 F.2d 1212, 211 USPQ 323 (CCPA 1981).” MPEP 2163.02 teaches that “Whenever the issue arises, the fundamental factual inquiry is whether a claim defines an invention that is clearly conveyed to those skilled in the art at the time the application was filed...If a claim is amended to include subject matter, limitations, or terminology not present in the application as filed, involving a departure from, addition to, or deletion from the disclosure of the application as filed, the examiner should conclude that the claimed subject matter is not described in that application”. MPEP 2163.06 further notes “When an amendment is filed in reply to an objection or rejection based on 35 U.S.C. 112, first paragraph, a study of the entire application is often necessary to determine whether or not “new matter” is involved. Applicant should therefore specifically point out the support for any amendments made to the disclosure” (emphasis added).
Applicant’s amendment to the independent claim encompasses an attempt to shift or otherwise change:
the broader genus of human subject/patient populations whose primary B cells are to be gene-edited and comprise naturally-occurring viral nucleic acids due to naturally-occurring viral infections to,
a subgenus of humans in which their B cells do not comprise any exogenous viral nucleic acids, as they have not experienced naturally-occurring viral infections,
for which there is no support in the instant specification and/or priority documents.
Those of ordinary skill in the art have long-recognized, for example, that the Epstein-Barr virus is naturally present in 19 out of 20 (syn. 95%) of the American human population, for example.
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The specification fails to disclose the primary human B cells with the negative limitation that are to be gene-edited are not infected with EBV, for example.
The specification fails to re-define the art-recognized exogenous EBV to be an endogenous (syn. not exogenous) viral nucleic acid, for example.
The specification is silent to “Epstein”, “Epstein-Barr”, “Epstein-Barr virus”, or “EBV”, for example.
The specification fails to disclose a step of selecting only those humans whose B cells do not comprise exogenous viral nucleic acids, from whom only this subpopulation of humans are to have their B cells genome-edited, for example.
The specification fails to disclose a step of selecting a subpopulation of primary human B cells that do not comprise exogenous viral nucleic acids from a heterogenous population of primary human B cells comprising B cells comprising exogenous viral nucleic acids to thereby only genome edit said subpopulation of primary human B cells that do not comprise exogenous viral nucleic acids, for example.
Applicant argues that support for the new limitation(s) is found in the specification because it does not disclose any steps for viral transformation of primary B cells.
Applicant’s argument is unpersuasive.
As a first matter, the negative limitation is not recited to be directed to the nucleic acid(s) by which the primary B cells are edited, let alone the exogenous transgene(s) encoding the exogenous heavy and/or light chain(s).
As a second matter, while the Product-by-Process step “transfected primary human B cells” is understood by the ordinary artisan to mean the gene editing system is introduced into the primary human B cells by means other than viral infection or viral transduction, e.g. liposomes or electroporation of a plasmid vector, Senis et al (CRISPR/Cas9-mediated genome engineering: An adeno-associated viral (AAV) vector toolbox, Biotechnol. J. 9: 1402-1412, DOI 10.1002/biot.201400046, available September 4, 2014) is considered relevant prior art for having taught the introduction of a CRISPR/Cas9 gene editing system into the artisan’s desired host cell via liposomal transfection of an AAV vector plasmid or infection/transduction of an AAV virus whose genome comprises said CRISPR/Cas9 system (e.g. pg 1404, Section 2.4, Transfection or transduction of CRISPR constructs).
Thus, here too, the specification fails to disclose the negative limitation whereby the CRISPR/Cas9 gene editing system transfected into the primary human B cells is not a plasmid encoding a viral vector encoding one or more components of the CRISPR/Cas9 system and/or donor templates.
As a third matter, Claim 48(iv) recites the presence of a non-native regulatory element, recited at a high level of generality, operably linked to the exogenous transgene(s) encoding the exogenous heavy and/or light chain(s). However, nowhere in the specification is it disclosed that the non-native regulatory element, recited at a high level of generality cannot be a viral regulatory element, e.g. a viral promoter or enhancer.
Scholz et al (U.S. 2013/0143267; of record) is considered relevant prior art for having disclosed primary B cells expressing a heterologous therapeutic antibody, whereby the antibody transgene is operably linked to a viral promoter (e.g. [0057], “heterologous viral promoters”) and/or a viral enhancer (e.g. [0061]), for example.
Thus, here too, the specification fails to disclose the negative limitation whereby the non-native regulatory element, recited at a high level of generality, operably linked to the exogenous transgene(s) encoding the exogenous heavy and/or light chain(s) is not a viral non-native regulatory element, even more specifically, not a viral promoter and/or a viral enhancer.
Alternatively, if Applicant believes that support for the negative limitation(s) now recited in amended Claim 23 and new Claims 44 and 48 is present and clearly envisaged in the instant application or earlier filed priority documents, applicant must, in responding to this Office Action, point out with particularity, where such support may be found.
Declarations and new references cannot demonstrate possession of a concept after the fact.
Applicant does not indicate where these limitations are supported by the original specification, or how, as is Applicant's burden. See MPEP §714.02, last sentence of the third paragraph from the end and MPEP §2163.06 (I) last sentence.
Thus, for the reasons outlined above, it is concluded that the claims do not meet the requirements for written description under 35 U.S.C. 112, first paragraph.
MPEP 2163 - 35 U.S.C. 112(a) and the first paragraph of pre-AIA 35 U.S.C. 112 require that the “specification shall contain a written description of the invention ....” This requirement is separate and distinct from the enablement requirement. Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1340, 94 USPQ2d 1161, 1167 (Fed. Cir. 2010) (en banc)
Dependent claims are included in the basis of the rejection because they do not correct the primary deficiencies of the independent claim(s).
4. Claim(s) 23, 34, 36, and 41-48 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as failing to set forth the subject matter which the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the applicant regards as the invention. Evidence that, at least, Claims 23 and 44 fail(s) to correspond in scope with that which the inventor or a joint inventor, or for pre-AIA applications the applicant regards as the invention can be found in the reply filed March 23, 2026. In that paper, the inventor or a joint inventor, or for pre-AIA applications the applicant has stated that the newly present negative limitation “lacks exogenous viral nucleic acids” is supported by the fact that the claimed gene-edited cells do not contain virally-transduced genes (e.g. pg 6, lines 2-3), and this statement indicates that the invention is different from what is defined in the claim(s) because instant Claims 23 and 44 fail to recite “virally-transduced genes”, nor refers to the vector(s) in which the gene editing system and/or donor template(s) encoding the exogenous heavy and/or light chains.
See further discussion in the above 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, New Matter rejection.
Dependent claims are included in the basis of the rejection because they do not correct the primary deficiencies of the independent claim(s).
5. Claim 43 is 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Applicant has amended Claim 23 to recite a population of genome-edited B cells, wherein said cells are not immortalized and lack exogenous viral nucleic acids.
Claim 43 recites wherein the genomes of the cells of the population of Claim 23 correspond to that of non-immortalized cells.
The phrase “correspond to” in Claim 43 is a relative term which renders the claim indefinite. The phrase “correspond to” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
As a first matter, the phrase denotes an unrecited and undisclosed number of changes to the genome of the cells of the population of Claim 23 which “corresponds to” the genome of some unrecited and undisclosed reference cell, as opposed to an unrecited and undisclosed number of changes to the genome of the cells of the population of Claim 23 which does not “corresponds to” the genome of some unrecited and undisclosed reference cell. Thus, that which does/does not “correspond to” is considered an arbitrary and subjective determination.
The recitation implies a genus of structurally unrecited and undisclosed genomes, by which “correspond to” is to be determined and/or identified, thereby rendering the claim indefinite. A claim may be rendered indefinite by reference to an object that is variable. (MPEP §2173.05(b)).
As a second matter, the claim recites the referenced non-immortalized cells at a high level of generality. Wikipedia (List of distinct cell types in the adult human body; Wikipedia.org/wiki/ List_of_distinct_cell_types_in_the_adult_human_body; last visited June 13, 2024) evidences that there are at least 1000 different cell types.
Even if one considers the referenced non-immortalized cell to be a primary human B cell, the breadth of the claims encompass B cells in which the BCR genes have not yet been re-arranged, as well as B cells in which the BCR genes have been re-arranged. Thus, here too, the non-immortalized cell type which does/does not “correspond to” the cells of the population of Claim 23 is considered an arbitrary and subjective determination.
The recitation implies a genus of structurally unrecited and undisclosed non-immortalized cells, by which “correspond to” is to be determined and/or identified, thereby rendering the claim indefinite. A claim may be rendered indefinite by reference to an object that is variable. (MPEP §2173.05(b)).
6. Claim 43 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Applicant has amended Claim 23 to recite a population of genome-edited B cells, wherein said cells are not immortalized and lack exogenous viral nucleic acids.
Claim 43 recites wherein the genomes of the cells of the population of Claim 23 correspond to that of non-immortalized cells.
Either this is an inherent property of (that naturally flows from) the cells of independent Claim 23, or it is not, and something of the cells of Claim 23 must change.
To the extent it is an inherent property of (that naturally flows from) the cells of the independent claim, then the instant claim fails to further limit the independent claim.
Furthermore, in regard to instant claims, it is noted that the "wherein the genomes….correspond to that of non-immortalized cells" clause does not recite any additional structure(s) and/or method steps, but simply states a characterization or conclusion of the results of genome-edited B cells, wherein said cells are not immortalized and lack exogenous viral nucleic acids, positively recited in the independent claim. Therefore, the "wherein" clause is not considered to further limit the method defined by the claim and has not been given weight in construing the claims. See Texas Instruments, Inc. v. International Trade Comm., 988 F.2d 1165, 1171,26 USPQ2d 1018, 1023 (Fed Cir. 1993) ("A 'whereby' clause that merely states the result of the limitations in the claim adds nothing to the patentability or substance of the claim."). See also Minton v. National Assoc. of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003) ("A whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.").
The Examiner incorporates herein the above 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, rejection.
The claims fail to recite, and the specification fails to disclose, a population of primary human genome-edited B cells, wherein said cells are not immortalized and lack exogenous viral nucleic acids yet do not correspond to that of non-immortalized cells.
Further still, it is axiomatic that the thus-edited primary human B cells genomes correspond to the source primary human B cells prior to gene-editing, but for the positively recited gene edit(s).
'Even if such a phrase did hold patentable weight, the phrase would likely be rejected under 35 USC 112(b) for being indefinite because such a phrase would amount to a 'functional limitation' whereby one of ordinary skill in the art would essentially need to 'guess' what steps must occur in the claim, in addition to the positively-recited method steps, in order to result in 'wherein the....' (the 'intended result' phrase in the claim).
The Examiner incorporates herein the above 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, rejection.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
7. Claim(s) 43 is 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.
Applicant has amended Claim 23 to recite a population of genome-edited B cells, wherein said cells are not immortalized and lack exogenous viral nucleic acids.
Claim 43 recites wherein the genomes of the cells of the population of Claim 23 correspond to that of non-immortalized cells.
Either this is an inherent property of (that naturally flows from) the cells of independent Claim 23, or it is not, and something of the cells of Claim 23 must change.
To the extent it is not an inherent property of (that naturally flows from) the cells of the independent claim, then the instant claim is considered to lack adequate written description for failing to recite the required structural change(s).
Furthermore, in regard to instant claims, it is noted that the "wherein the genomes….correspond to that of non-immortalized cells" clause does not recite any additional structure(s) and/or method steps, but simply states a characterization or conclusion of the results of genome-edited B cells, wherein said cells are not immortalized and lack exogenous viral nucleic acids, positively recited in the independent claim. Therefore, the "wherein" clause is not considered to further limit the method defined by the claim and has not been given weight in construing the claims. See Texas Instruments, Inc. v. International Trade Comm., 988 F.2d 1165, 1171,26 USPQ2d 1018, 1023 (Fed Cir. 1993) ("A 'whereby' clause that merely states the result of the limitations in the claim adds nothing to the patentability or substance of the claim."). See also Minton v. National Assoc. of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003) ("A whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.").
The claims fail to recite, and the specification fails to disclose, a population of primary human genome-edited B cells, wherein said cells are not immortalized and lack exogenous viral nucleic acids yet do not correspond to that of non-immortalized cells.
Further still, it is axiomatic that the thus-edited primary human B cells genomes correspond to the source primary human B cells prior to gene-editing, but for the positively recited gene edit(s).
'Even if such a phrase did hold patentable weight, the phrase would likely be rejected under 35 USC 112(b) for being indefinite because such a phrase would amount to a 'functional limitation' whereby one of ordinary skill in the art would essentially need to 'guess' what steps must occur in the claim, in addition to the positively-recited method steps, in order to result in 'wherein the....' (the 'intended result' phrase in the claim).
MPEP 2163 - 35 U.S.C. 112(a) and the first paragraph of pre-AIA 35 U.S.C. 112 require that the “specification shall contain a written description of the invention ....” This requirement is separate and distinct from the enablement requirement. Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1340, 94 USPQ2d 1161, 1167 (Fed. Cir. 2010) (en banc)
8. Claim 44 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Applicant has amended Claim 23 to recite a population of genome-edited B cells, wherein said cells are not immortalized and lack exogenous viral nucleic acids.
Claim 44 recites wherein the genomes of the cells of the population of Claim 23 lack exogenous viral nucleic acids.
Claim 44 fails to further limit the independent claim because Claim 23 already recites that the population of genome-edited B cells lack exogenous viral nucleic acids.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
9. Claim 45 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Applicant has amended Claim 23 to recite a population of genome-edited B cells, wherein said cells are not immortalized and lack exogenous viral nucleic acids.
Claim 45 recites wherein the cells of the population are non-proliferative unless activated with IL-4, IL-21, CD40L, or combinations thereof.
Either this is an inherent property of (that naturally flows from) the cells of independent Claim 23, or it is not, and something of the cells of Claim 23 must change.
To the extent it is an inherent property of (that naturally flows from) the cells of the independent claim, then the instant claim fails to further limit the independent claim.
Furthermore, in regard to instant claims, it is noted that the "wherein…. are non-proliferative unless activated with IL-4, IL-21, CD40L, or combinations thereof " clause does not recite any additional structure(s) and/or method steps, but simply states a characterization or conclusion of the results of genome-edited B cells, wherein said cells are not immortalized and lack exogenous viral nucleic acids, positively recited in the independent claim. Therefore, the "wherein" clause is not considered to further limit the method defined by the claim and has not been given weight in construing the claims. See Texas Instruments, Inc. v. International Trade Comm., 988 F.2d 1165, 1171,26 USPQ2d 1018, 1023 (Fed Cir. 1993) ("A 'whereby' clause that merely states the result of the limitations in the claim adds nothing to the patentability or substance of the claim."). See also Minton v. National Assoc. of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003) ("A whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.").
The claims fail to recite, and the specification fails to disclose, a population of primary human genome-edited B cells, wherein said cells are not immortalized and lack exogenous viral nucleic acids yet are not non-proliferative unless activated with IL-4, IL-21, CD40L, or combinations thereof.
'Even if such a phrase did hold patentable weight, the phrase would likely be rejected under 35 USC 112(b) for being indefinite because such a phrase would amount to a 'functional limitation' whereby one of ordinary skill in the art would essentially need to 'guess' what steps must occur in the claim, in addition to the positively-recited method steps, in order to result in 'wherein the....' (the 'intended result' phrase in the claim).
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
10. Claim(s) 45 is 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.
Applicant has amended Claim 23 to recite a population of genome-edited B cells, wherein said cells are not immortalized and lack exogenous viral nucleic acids.
Claim 45 recites wherein the cells of the population are non-proliferative unless activated with IL-4, IL-21, CD40L, or combinations thereof.
Either this is an inherent property of (that naturally flows from) the cells of independent Claim 23, or it is not, and something of the cells of Claim 23 must change.
The claim denotes that not all populations of genome-edited B cells, wherein said cells are not immortalized and lack exogenous viral nucleic acids of Claim 23 have the functional property(ies) now recited in dependent Claim 45.
To the extent it is not an inherent property of (that naturally flows from) the cells of the independent claim, then the instant claim is considered to lack adequate written description for failing to recite the required structural change(s).
In analyzing whether the written description requirement is met for genus claims, it is first determined whether a representative number of species have been described by their complete structure. To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof. The disclosure of a single species is rarely, if ever, sufficient to describe a broad genus, particularly when the specification fails to describe the features of that genus, even in passing. (see In re Shokal 113USPQ283(CCPA1957); Purdue Pharma L.P. vs Faulding Inc. 56 USPQ2nd 1481 (CAFC 2000).
The court explained that “reading a claim in light of the specification, to thereby interpret limitations explicitly recited in the claim, is a quite different thing from ‘reading limitations of the specification into a claim,’ to thereby narrow the scope of the claim by implicitly adding disclosed limitations which have no express basis in the claim.” The court found that applicant was advocating the latter, i.e., the impermissible importation of subject matter from the specification into the claim.). See also In re Morris, 127 F.3d 1048, 1054-55, 44 USPQ2d 1023, 1027-28 (Fed. Cir. 1997).
The claims fail to recite, and the specification fails to disclose, a population of primary human genome-edited B cells, wherein said cells are not immortalized and lack exogenous viral nucleic acids yet are not non-proliferative unless activated with IL-4, IL-21, CD40L, or combinations thereof.
The claims fail to recite, and the specification fails to disclose, a first population of primary human genome-edited B cells, wherein said cells are not immortalized and lack exogenous viral nucleic acids yet are not non-proliferative unless activated with IL-4, IL-21, CD40L, or combinations thereof, as opposed to a second population of primary human genome-edited B cells, wherein said cells are not immortalized and lack exogenous viral nucleic acids and are non-proliferative unless activated with IL-4, IL-21, CD40L, or combinations thereof, for example.
The claims fail to recite, and the specification fails to disclose, how to modify or otherwise transform a first population of primary human genome-edited B cells, wherein said cells are not immortalized and lack exogenous viral nucleic acids yet are not non-proliferative unless activated with IL-4, IL-21, CD40L, or combinations thereof, into a second population of primary human genome-edited B cells, wherein said cells are not immortalized and lack exogenous viral nucleic acids and are now, necessarily and predictably, non-proliferative unless activated with IL-4, IL-21, CD40L, or combinations thereof, for example.
Furthermore, in regard to instant claims, it is noted that the "wherein…. are non-proliferative unless activated with IL-4, IL-21, CD40L, or combinations thereof " clause does not recite any additional structure(s) and/or method steps, but simply states a characterization or conclusion of the results of genome-edited B cells, wherein said cells are not immortalized and lack exogenous viral nucleic acids, positively recited in the independent claim. Therefore, the "wherein" clause is not considered to further limit the method defined by the claim and has not been given weight in construing the claims. See Texas Instruments, Inc. v. International Trade Comm., 988 F.2d 1165, 1171,26 USPQ2d 1018, 1023 (Fed Cir. 1993) ("A 'whereby' clause that merely states the result of the limitations in the claim adds nothing to the patentability or substance of the claim."). See also Minton v. National Assoc. of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003) ("A whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.").
'Even if such a phrase did hold patentable weight, the phrase would likely be rejected under 35 USC 112(b) for being indefinite because such a phrase would amount to a 'functional limitation' whereby one of ordinary skill in the art would essentially need to 'guess' what steps must occur in the claim, in addition to the positively-recited method steps, in order to result in 'wherein the....' (the 'intended result' phrase in the claim).
MPEP 2163 - 35 U.S.C. 112(a) and the first paragraph of pre-AIA 35 U.S.C. 112 require that the “specification shall contain a written description of the invention ....” This requirement is separate and distinct from the enablement requirement. Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1340, 94 USPQ2d 1161, 1167 (Fed. Cir. 2010) (en banc)
11. Claim 46 is 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The phrases “exhibit apoptotic sensitivity” and “is mitigated” in Claim 46 is/are a relative phrase(s) which render(s) the claim indefinite. The phrases “exhibit apoptotic sensitivity” and “is mitigated” is/are not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
The recitation implies a genus of unrecited phenotypes, by which “exhibit apoptotic sensitivity” and/or “is mitigated” is/are to be determined and/or identified, thereby rendering the claim indefinite. A claim may be rendered indefinite by reference to an object that is variable. (MPEP §2173.05(b)).
The apoptotic inhibitor is recited at a high level of generality, and thus the recitation implies a genus of unrecited apoptotic inhibitor compounds/agents to be referenced from which “exhibit apoptotic sensitivity” and/or “is mitigated” is/are is to be determined and/or identified, thereby rendering the claim indefinite. A claim may be rendered indefinite by reference to an object that is variable. (MPEP §2173.05(b)).
12. Claim 46 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Applicant has amended Claim 23 to recite a population of genome-edited B cells, wherein said cells are not immortalized and lack exogenous viral nucleic acids.
Claim 46 recites wherein the cells of the population exhibit apoptotic sensitivity that is mitigated by culture in presence of an apoptotic inhibitor.
Either this is an inherent property of (that naturally flows from) the cells of independent Claim 23, or it is not, and something of the cells of Claim 23 must change.
To the extent it is an inherent property of (that naturally flows from) the cells of the independent claim, then the instant claim fails to further limit the independent claim.
Furthermore, in regard to instant claims, it is noted that the "wherein…. the cells of the population exhibit apoptotic sensitivity that is mitigated by culture in presence of an apoptotic inhibitor" clause does not recite any additional structure(s) and/or method steps, but simply states a characterization or conclusion of the results of genome-edited B cells, wherein said cells are not immortalized and lack exogenous viral nucleic acids, positively recited in the independent claim. Therefore, the "wherein" clause is not considered to further limit the method defined by the claim and has not been given weight in construing the claims. See Texas Instruments, Inc. v. International Trade Comm., 988 F.2d 1165, 1171,26 USPQ2d 1018, 1023 (Fed Cir. 1993) ("A 'whereby' clause that merely states the result of the limitations in the claim adds nothing to the patentability or substance of the claim."). See also Minton v. National Assoc. of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003) ("A whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.").
The claims fail to recite, and the specification fails to disclose, a population of primary human genome-edited B cells, wherein said cells are not immortalized and lack exogenous viral nucleic acids yet do not exhibit apoptotic sensitivity that is mitigated by culture in presence of an apoptotic inhibitor.
'Even if such a phrase did hold patentable weight, the phrase would likely be rejected under 35 USC 112(b) for being indefinite because such a phrase would amount to a 'functional limitation' whereby one of ordinary skill in the art would essentially need to 'guess' what steps must occur in the claim, in addition to the positively-recited method steps, in order to result in 'wherein the....' (the 'intended result' phrase in the claim).
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
13. Claim(s) 46 is 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.
Applicant has amended Claim 23 to recite a population of genome-edited B cells, wherein said cells are not immortalized and lack exogenous viral nucleic acids.
Claim 46 recites wherein the cells of the population exhibit apoptotic sensitivity that is mitigated by culture in presence of an apoptotic inhibitor.
Either this is an inherent property of (that naturally flows from) the cells of independent Claim 23, or it is not, and something of the cells of Claim 23 must change.
The claim denotes that not all populations of genome-edited B cells, wherein said cells are not immortalized and lack exogenous viral nucleic acids of Claim 23 have the functional property(ies) now recited in dependent Claim 46.
To the extent it is not an inherent property of (that naturally flows from) the cells of the independent claim, then the instant claim is considered to lack adequate written description for failing to recite the required structural change(s).
In analyzing whether the written description requirement is met for genus claims, it is first determined whether a representative number of species have been described by their complete structure. To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof. The disclosure of a single species is rarely, if ever, sufficient to describe a broad genus, particularly when the specification fails to describe the features of that genus, even in passing. (see In re Shokal 113USPQ283(CCPA1957); Purdue Pharma L.P. vs Faulding Inc. 56 USPQ2nd 1481 (CAFC 2000).
The court explained that “reading a claim in light of the specification, to thereby interpret limitations explicitly recited in the claim, is a quite different thing from ‘reading limitations of the specification into a claim,’ to thereby narrow the scope of the claim by implicitly adding disclosed limitations which have no express basis in the claim.” The court found that applicant was advocating the latter, i.e., the impermissible importation of subject matter from the specification into the claim.). See also In re Morris, 127 F.3d 1048, 1054-55, 44 USPQ2d 1023, 1027-28 (Fed. Cir. 1997).
The claims fail to recite, and the specification fails to disclose, a population of primary human genome-edited B cells, wherein said cells are not immortalized and lack exogenous viral nucleic acids yet do not exhibit apoptotic sensitivity that is mitigated by culture in presence of an apoptotic inhibitor.
The claims fail to recite, and the specification fails to disclose, a first population of primary human genome-edited B cells, wherein said cells are not immortalized and lack exogenous viral nucleic acids yet do not exhibit apoptotic sensitivity that is mitigated by culture in presence of an apoptotic inhibitor (recited at a high level of generality), as opposed to a second population of primary human genome-edited B cells, wherein said cells are not immortalized and lack exogenous viral nucleic acids and exhibit apoptotic sensitivity that is mitigated by culture in presence of an apoptotic inhibitor, for example.
The claims fail to recite, and the specification fails to disclose, how to modify or otherwise transform a first population of primary human genome-edited B cells, wherein said cells are not immortalized and lack exogenous viral nucleic acids yet do not exhibit apoptotic sensitivity that is mitigated by culture in presence of an apoptotic inhibitor (recited at a high level of generality), into a second population of primary human genome-edited B cells, wherein said cells are not immortalized and lack exogenous viral nucleic acids and now, necessarily and predictably, do exhibit apoptotic sensitivity that is mitigated by culture in presence of an apoptotic inhibitor, for example.
Furthermore, in regard to instant claims, it is noted that the "wherein…. the cells of the population exhibit apoptotic sensitivity that is mitigated by culture in presence of an apoptotic inhibitor" clause does not recite any additional structure(s) and/or method steps, but simply states a characterization or conclusion of the results of genome-edited B cells, wherein said cells are not immortalized and lack exogenous viral nucleic acids, positively recited in the independent claim. Therefore, the "wherein" clause is not considered to further limit the method defined by the claim and has not been given weight in construing the claims. See Texas Instruments, Inc. v. International Trade Comm., 988 F.2d 1165, 1171,26 USPQ2d 1018, 1023 (Fed Cir. 1993) ("A 'whereby' clause that merely states the result of the limitations in the claim adds nothing to the patentability or substance of the claim."). See also Minton v. National Assoc. of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003) ("A whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.").
'Even if such a phrase did hold patentable weight, the phrase would likely be rejected under 35 USC 112(b) for being indefinite because such a phrase would amount to a 'functional limitation' whereby one of ordinary skill in the art would essentially need to 'guess' what steps must occur in the claim, in addition to the positively-recited method steps, in order to result in 'wherein the....' (the 'intended result' phrase in the claim).
MPEP 2163 - 35 U.S.C. 112(a) and the first paragraph of pre-AIA 35 U.S.C. 112 require that the “specification shall contain a written description of the invention ....” This requirement is separate and distinct from the enablement requirement. Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1340, 94 USPQ2d 1161, 1167 (Fed. Cir. 2010) (en banc)
14. Claim 47 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 23 recites a population of genome-edited primary human B cells, wherein said cells are not immortalized and lack exogenous viral nucleic acids.
Claim 47 recites wherein the cells of the population are either allogeneic or autologous to a subject into whom the population is transplanted.
As a first matter, the recitation “a subject” (Claim 47, line 2) is broader in scope than the Claim 23 preamble “human-transplantable population”, as it would appear to encompass non-human subjects (e.g. [000214], “A subject in the context of the present invention is preferably a mammal, … can be a non-human primate, mouse, rat, dog, …”). Those of ordinary skill in the art immediately recognize that human cells are not allogeneic nor autologous to non-human animals.
As a second matter, those of ordinary skill in the art immediately recognize that primary human B cells (Claim 23) are inherently either allogeneic or autologous to human subjects, per natural law of biology. Thus, mere recitation of both embodiments fails to further limit the independent claim.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
15. Claim 48 is 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The phrases “junction sequence unique” in Claim 48(i) is a relative phrase which render(s) the claim indefinite. The term “unique” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
The recitation implies a genus of unrecited junction sequences, e.g. variable regions of recombined heavy chain region, variable regions of light chain regions, junctions between heavy chain variable, joining, and/or constant regions, junctions between light chain variable and/or constant regions, 5’ donor template integration site sequences, and/or 3’ donor template integration site sequences, and corresponding unrecited and undisclosed genotypes, by which “unique” is/are to be determined and/or identified, thereby rendering the claim indefinite. A claim may be rendered indefinite by reference to an object that is variable. (MPEP §2173.05(b)).
That which is/is not considered to be “unique” is considered an arbitrary and subjective determination.
16. Claim 48 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 23 recites a population of genome-edited primary human B cells, wherein said cells are not immortalized and lack exogenous viral nucleic acids.
Claim 48(i) recites the limitation wherein the junction sequence is unique to the inserted heavy or light chains of the defined therapeutic antibody.
Either this is an inherent property of (that naturally flows from) the cells of independent Claim 23, or it is not, and something of the cells of Claim 23 must change.
To the extent it is an inherent property of (that naturally flows from) the cells of the independent claim, then the instant claim fails to further limit the independent claim.
Furthermore, in regard to instant claims, it is noted that the "wherein…. the junction sequence is unique to the inserted heavy or light chains of the defined therapeutic antibody" clause does not recite any additional structure(s) and/or method steps, but simply states a characterization or conclusion of the results of genome-edited B cells, wherein said cells are not immortalized and lack exogenous viral nucleic acids, positively recited in the independent claim. Therefore, the "wherein" clause is not considered to further limit the method defined by the claim and has not been given weight in construing the claims. See Texas Instruments, Inc. v. International Trade Comm., 988 F.2d 1165, 1171,26 USPQ2d 1018, 1023 (Fed Cir. 1993) ("A 'whereby' clause that merely states the result of the limitations in the claim adds nothing to the patentability or substance of the claim."). See also Minton v. National Assoc. of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003) ("A whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.").
The Examiner incorporates herein the above 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, rejection.
The recitation implies a genus of unrecited junction sequences, e.g. variable regions of recombined heavy chain region, variable regions of light chain regions, junctions between heavy chain variable, joining, and/or constant regions, junctions between light chain variable and/or constant regions, 5’ donor template integration site sequences, and/or 3’ donor template integration site sequences, and corresponding unrecited and undisclosed genotypes, by which “unique” is/are to be determined and/or identified, thereby rendering the claim indefinite. A claim may be rendered indefinite by reference to an object that is variable. (MPEP §2173.05(b)).
Applicant argues for support of the limitation per the PCR detection of sequences across the junctions of the donor template integrated into the endogenous heavy or light chain sequences of the primary human B cell (e.g. Remarks Made in Amendment, pg 6, para 6).
However, such merely refers to the results achieved per natural law of cell biology, enzymology, and DNA repair mechanisms.
The claims fail to recite, and the specification fails to disclose, a population of primary human genome-edited B cells, wherein said cells are not immortalized and lack exogenous viral nucleic acids (Claim 23) yet do not possess a junction sequence unique to the inserted heavy or light chains of the defined therapeutic antibody (do not satisfy Claim 48(i)), in defiance of natural law of cell biology, enzymology, and DNA repair mechanisms.
'Even if such a phrase did hold patentable weight, the phrase would likely be rejected under 35 USC 112(b) for being indefinite because such a phrase would amount to a 'functional limitation' whereby one of ordinary skill in the art would essentially need to 'guess' what steps must occur in the claim, in addition to the positively-recited method steps, in order to result in 'wherein the....' (the 'intended result' phrase in the claim).
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
17. Claim(s) 48 is 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.
Claim 23 recites a population of genome-edited primary human B cells, wherein said cells are not immortalized and lack exogenous viral nucleic acids.
Claim 48(i) recites the limitation wherein the junction sequence is unique to the inserted heavy or light chains of the defined therapeutic antibody.
In analyzing whether the written description requirement is met for genus claims, it is first determined whether a representative number of species have been described by their complete structure. To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof. The disclosure of a single species is rarely, if ever, sufficient to describe a broad genus, particularly when the specification fails to describe the features of that genus, even in passing. (see In re Shokal 113USPQ283(CCPA1957); Purdue Pharma L.P. vs Faulding Inc. 56 USPQ2nd 1481 (CAFC 2000).
The court explained that “reading a claim in light of the specification, to thereby interpret limitations explicitly recited in the claim, is a quite different thing from ‘reading limitations of the specification into a claim,’ to thereby narrow the scope of the claim by implicitly adding disclosed limitations which have no express basis in the claim.” The court found that applicant was advocating the latter, i.e., the impermissible importation of subject matter from the specification into the claim.). See also In re Morris, 127 F.3d 1048, 1054-55, 44 USPQ2d 1023, 1027-28 (Fed. Cir. 1997).
The Examiner incorporates herein the above 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, rejection.
The phrases “junction sequence unique” in Claim 48(i) is a relative phrase which render(s) the claim indefinite. The term “unique” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
The recitation implies a genus of unrecited junction sequences, e.g. variable regions of recombined heavy chain region, variable regions of light chain regions, junctions between heavy chain variable, joining, and/or constant regions, junctions between light chain variable and/or constant regions, 5’ donor template integration site sequences, and/or 3’ donor template integration site sequences, and corresponding unrecited and undisclosed genotypes, by which “unique” is/are to be determined and/or identified, thereby rendering the claim indefinite. A claim may be rendered indefinite by reference to an object that is variable. (MPEP §2173.05(b)).
That which is/is not considered to be “unique” is considered an arbitrary and subjective determination.
Applicant argues for support of the limitation per the PCR detection of sequences across the junctions of the donor template integrated into the endogenous heavy or light chain sequences of the primary human B cell (e.g. Remarks Made in Amendment, pg 6, para 6).
However, such merely refers to the results achieved per natural law of cell biology, enzymology, and DNA repair mechanisms.
The claims fail to recite, and the specification fails to disclose, a population of primary human genome-edited B cells, wherein said cells are not immortalized and lack exogenous viral nucleic acids (Claim 23) yet do not possess a junction sequence unique to the inserted heavy or light chains of the defined therapeutic antibody (do not satisfy Claim 48(i)), in defiance of natural law of cell biology, enzymology, and DNA repair mechanisms.
The claims fail to recite, and the specification fails to disclose, a first population of primary human genome-edited B cells, wherein said cells are not immortalized and lack exogenous viral nucleic acids yet do not exhibit a unique junction sequence (recited at a high level of generality), as opposed to a second population of primary human genome-edited B cells, wherein said cells are not immortalized and lack exogenous viral nucleic acids and do exhibit a unique junction sequence, for example.
The claims fail to recite, and the specification fails to disclose, how to modify or otherwise transform a first gene editing method producing a population of primary human genome-edited B cells, wherein said cells are not immortalized and lack exogenous viral nucleic acids yet do not exhibit a unique junction sequence (recited at a high level of generality), into a second gene editing method producing a population of primary human genome-edited B cells, wherein said cells are not immortalized and lack exogenous viral nucleic acids and now, necessarily and predictably, do exhibit a unique junction sequence, for example.
Furthermore, in regard to instant claims, it is noted that the "wherein…. the junction sequence is unique to the inserted heavy or light chains of the defined therapeutic antibody" clause does not recite any additional structure(s) and/or method steps, but simply states a characterization or conclusion of the results of genome-edited B cells, wherein said cells are not immortalized and lack exogenous viral nucleic acids, positively recited in the independent claim. Therefore, the "wherein" clause is not considered to further limit the method defined by the claim and has not been given weight in construing the claims. See Texas Instruments, Inc. v. International Trade Comm., 988 F.2d 1165, 1171,26 USPQ2d 1018, 1023 (Fed Cir. 1993) ("A 'whereby' clause that merely states the result of the limitations in the claim adds nothing to the patentability or substance of the claim."). See also Minton v. National Assoc. of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003) ("A whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.").
'Even if such a phrase did hold patentable weight, the phrase would likely be rejected under 35 USC 112(b) for being indefinite because such a phrase would amount to a 'functional limitation' whereby one of ordinary skill in the art would essentially need to 'guess' what steps must occur in the claim, in addition to the positively-recited method steps, in order to result in 'wherein the....' (the 'intended result' phrase in the claim).
MPEP 2163 - 35 U.S.C. 112(a) and the first paragraph of pre-AIA 35 U.S.C. 112 require that the “specification shall contain a written description of the invention ....” This requirement is separate and distinct from the enablement requirement. Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1340, 94 USPQ2d 1161, 1167 (Fed. Cir. 2010) (en banc)
Claim Rejections - 35 USC § 103
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 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 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 of this title, 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(a) 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.
18. Claims 23, 34, 36, and 41-48 are rejected under AIA 35 U.S.C. 103 as being unpatentable over Scholz et al (U.S. 2013/0143267; of record) in view of Buelow et al (U.S. 2007/0033661; of record), Hyde et al (U.S. 2013/0164277; of record), Ando et al (U.S. 2008/0159996; of record), Wang et al (available online August 25, 2014; of record), and Mandal et al (available online November 6, 2014; of record cited).
Determining the scope and contents of the prior art, and Ascertaining the differences between the prior art and the claims at issue.
Applicant has amended Claim 23 to recite “transplantable population of genome-edited B cells”.
A recitation of the intended use of the claimed invention 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. If the prior art structure is capable of performing the intended use, then it meets the claim. The phrase “transplantable…” is an intended use limitation, which does not contain any further structural limitations with respect to claimed primary human B cell(s) whose genome comprises a nucleic acid sequence encoding the variable regions of light and heavy chains of a heterologous therapeutic antibody recited in the independent claims (see MPEP §2114).
Instant specification fails to disclose a first population of genome-edited primary human B cells comprising the claimed gene-edits [structures] which are not “transplantable…”, as opposed to a second population of genome-edited primary human B cells comprising the claimed gene-edits [structures] which are “transplantable…”.
To the extent Applicant argues otherwise, see above 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, written description rejection.
Applicant has amended Claim 23 to recite “transfected primary human B cells”.
The recitation of a process limitation in Claim 23 is not viewed as positively limiting the claimed product of Claim 23 absent a showing that the process of making recited in the dependent claims imparts a novel or unexpected property to the claimed product, as it is assumed that equivalent products are obtainable by multiple routes. The method in which the primary human B cell(s) whose genome comprises a nucleic acid sequence encoding the variable regions of light and heavy chains of a heterologous therapeutic antibody recited in the independent claims were produced is immaterial to their patentability.
"Even though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 227 USPQ 964, 966 (Fed. Cir. 1985). See also MPEP §2113.
There is no objective evidence that genome-edited primary human B cells comprising the claimed gene-edits [structures] made via transfection to introduce the heterologous nucleic acids are molecularly distinguishable from genome-edited primary human B cells comprising the claimed gene-edits [structures] made via other means of introducing the heterologous nucleic acids, e.g. electroporation, nucleofection, and/or transduction.
With respect to Claim 23, Scholz et al is considered relevant prior art for having disclosed and successfully demonstrated the ability of the ordinary artisan to genetically modify resting B cells, including primary human B cells (e.g. [0022], “a source of B cells is obtained from a subject”, “Examples of subjects include humans”), to express a transgene of interest, wherein the transgene of interest is a monoclonal antibody (e.g. [0076, 87], b12 anti-HIV-1 neutralizing antibody; Example 1, primary human B cells transduced to successfully produce the HIV neutralizing antibody b12).
Scholz et al does not disclose wherein the heterologous monoclonal antibody transgenes encoding the heavy and/or light chains are inserted into the endogenous heavy or light chain loci.
However, prior to the effective filing date of the instantly claimed invention, and with respect to Claim(s) 23 and 36, Buelow et al is considered relevant prior art for having disclosed a population of somatic cells in which a human immunoglobulin locus transgene is either randomly inserted in the host B cell genome (as per Scholz et al) or replaces the endogenous immunoglobulin locus, e.g. via homologous recombination (e.g. [0112-113]), wherein the transgenic immunoglobulin locus encodes an immunoglobulin heavy chain or an immunoglobulin light chain (e.g. 0107]), and wherein the human immunoglobulin transgene encodes a monoclonal antibody (e.g. [0051, 55]). The exogenous immunoglobulins are expressed in B cells (e.g. [0038, 85]).
Similarly, Hyde et al is considered relevant prior art for having disclosed a population of B cells isolated from an individual ([0037], “isolating human B cells from an individual”), whereby the endogenous immunoglobulin heavy and light genes encoding a B cell receptor are deleted, being replaced via homologous recombination with a heterologous nucleic acid encoding the artisan’s immunoglobulin heavy and light chain genes [0037, 73].
The heterologous antibody is a monoclonal antibody (e.g. [0069], “isolated from the chromosomal DNA of a human B cell clone that produces the antibody”).
The artisan’s heterologous therapeutic immunoglobulin heavy and light chain genes may replace:
a) the endogenous functional immunoglobulin heavy and light chain genes (e.g. [0037], Example 5, [0111], anti-S. aureus PNAG antibody), and/or,
b) the endogenous non-functional immunoglobulin heavy and light chain genes (e.g. [0037], Example 2, [0082], anti-HCV antibody).
The artisan’s heterologous immunoglobulin heavy and light chain genes may be specific for influenza [0038], e.g. an anti-influenza broadly neutralizing antibody secreted from the B cell ([0042], “secreted anti-influenza broadly neutralizing antibodies”), or HCV (e.g. [0082], the replacement Ig genes…encode a secreted anti-HCV antibody), or S. aureus pathogen (e.g. Example 5, [0111], anti-S. aureus PNAG antibody, [0107], secreted immunoglobulins to methicillin-resistant S. aureus (MRSA)).
Hyde et al disclosed and successfully demonstrated the ability to transfect primary B cells with a nucleic acid encoding an immunoglobulin molecule (e.g. [0045, 47, 49], “transfected with”).
With respect to the newly introduced limitation wherein the cells of the population are not immortalized, there is no objective evidence that the primary human B cells expressing a heterologous therapeutic antibody are immortalized.
With respect to the newly introduced limitation wherein the cells of the population lack exogenous viral nucleic acids, and in light of Applicant’s remarks indicating that this negative limitation refers to the donor template introduced into the endogenous heavy or light chain gene,
Buelow et al disclosed a population of somatic cells in which a human immunoglobulin locus transgene replaces the endogenous immunoglobulin locus, e.g. via homologous recombination (e.g. [0112-113]). There is no objective evidence that the genome-edited primary human B cells of Buelow et al in which the endogenous heavy or light chain locus is genome-edited with a heterologous immunoglobulin locus transgene comprises exogenous viral nucleic acids.
Hyde et al disclosed a population of B cells isolated from an individual ([0037], “isolating human B cells from an individual”), whereby the endogenous immunoglobulin heavy and light genes encoding a B cell receptor are deleted, being replaced via homologous recombination with a heterologous nucleic acid encoding the artisan’s immunoglobulin heavy and light chain genes [0037, 73]. There is no objective evidence that the genome-edited primary human B cells of Hyde et al in which the endogenous heavy or light chain locus is genome-edited with a heterologous immunoglobulin locus transgene comprises exogenous viral nucleic acids.
With respect to the ability of the ordinary artisan to edit the genome of primary human B cells with a reasonable expectation of success:
Ando et al is considered relevant prior art for having disclosed the use of ZFNs to edit the genome of primary human T cells, thereby resulting in the targeted insertion of an exogenous nucleic acid sequence into a targeted location of the T cell genome (Example 5), and disclosed the ZFNs may also be used in B cells and other T cell subtypes [0122].
Wang et al is considered relevant prior art for having successfully demonstrated the use of the CRISPR/Cas9 system to edit the genome of human B cells, e.g. Raji cells (e.g. Figures 1-2).
Mandal et al is considered relevant prior art for having successfully demonstrated the ability of the ordinary artisan to use the CRISPR/Cas9 gene editing system to target and edit the artisan’s gene(s) of interest in primary human T cells and primary human hematopoietic stem cells (HSCs) (entire paper, Graphical Abstract; Summary, “primary human CD4+ T cells”).
Resolving the level of ordinary skill in the pertinent art.
People of the ordinary skill in the art will be highly educated individuals such as medical doctors, scientists, or engineers possessing advanced degrees, including M.D.'s and Ph.D.'s. Thus, these people most likely will be knowledgeable and well-read in the relevant literature and have the practical experience in molecular biology, immunology, cell biology, and gene editing technologies. Therefore, the level of ordinary skill in this art is high.
"A person of ordinary skill in the art is also a person of ordinary creativity, not an automaton." KSR International Co. v. Teleflex Inc., 550 U.S. ___, ___, 82 USPQ2d 1385, 1397 (2007). "[I]n many cases a person of ordinary skill will be able to fit the teachings of multiple patents together like pieces of a puzzle." Id. Office personnel may also take into account "the inferences and creative steps that a person of ordinary skill in the art would employ." Id. at ___, 82 USPQ2d at 1396.
Considering objective evidence present in the application indicating obviousness or nonobviousness.
The focus when making a determination of obviousness should be on what a person of ordinary skill in the pertinent art would have known at the time of the invention, and on what such a person would have reasonably expected to have been able to do in view of that knowledge. This is so regardless of whether the source of that knowledge and ability was documentary prior art, general knowledge in the art, or common sense. M.P.E.P. §2141.
The rationale to modify or combine the prior art does not have to be expressly stated in the prior art; the rationale may be expressly or impliedly contained in the prior art or it may be reasoned from knowledge generally available to one of ordinary skill in the art, established scientific principles, or legal precedent established by prior case law. 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). See also In re Kotzab, 217 F.3d 1365, 1370, 55 USPQ2d 1313, 1317 (Fed. Cir. 2000) (setting forth test for implicit teachings); In re Eli Lilly & Co., 902 F.2d 943, 14 USPQ2d 1741 (Fed. Cir. 1990) (discussion of reliance on legal precedent); In re Nilssen, 851 F.2d 1401, 1403, 7 USPQ2d 1500, 1502 (Fed. Cir. 1988) (references do not have to explicitly suggest combining teachings); and Ex parte Levengood, 28 USPQ2d 1300 (Bd. Pat. App. & Inter. 1993) (reliance on logic and sound scientific reasoning). See MPEP §2144.
Prior to the effective filing date of the instantly claimed invention, it would have been obvious to one of ordinary skill in the art to substitute a first vector genomic location in which to insert the artisan’s therapeutic antibody heavy and light chain genes, e.g. random integration, as disclosed by Scholz et al and Buelow et al, with a second genomic location in which to insert the artisan’s therapeutic antibody heavy and light chain genes, to wit, replacement of the endogenous immunoglobulin heavy and light chain genes, as disclosed by Buelow et al and Hyde et al, in primary human B cells with a reasonable expectation of success because the simple substitution of one known element for another would have yielded predictable results to one of ordinary skill in the art at the time of the invention. M.P.E.P. §2144.07 states "The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945).” “Reading a list and selecting a known compound to meet known requirements is no more ingenious than selecting the last piece to put in the last opening in a jig-saw puzzle." 325 U.S. at 335, 65 USPQ at 301.).” When substituting equivalents known in the prior art for the same purpose, an express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982). M.P.E.P. §2144.06. An artisan would be motivated to substitute to substitute a first vector genomic location in which to insert the artisan’s therapeutic antibody heavy and light chain genes, e.g. random integration, with a second genomic location in which to insert the artisan’s therapeutic antibody heavy and light chain genes, to wit, replacement of the endogenous immunoglobulin heavy and light chain genes, in primary human B cells because those or ordinary skill in the art previously recognized and successfully reduced to practice the scientific and technical concepts of inserting the artisan’s therapeutic antibody heavy and light chain genes into the endogenous immunoglobulin heavy and light chain loci, and Buelow et al disclosed a population of somatic cells in which a human immunoglobulin locus transgene is either randomly inserted in the host B cell genome (as per Scholz et al) or replaces the endogenous immunoglobulin locus, e.g. via homologous recombination (e.g. [0112-113]).
It is obvious to one of ordinary skill in the art to choose from a finite number of identified, predictable options because “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipate success, it is likely that product not of innovation but of ordinary skill and common sense.” The ordinary artisan previously recognized that there is a finite list of potential options, e.g. random integration or insertion into the endogenous immunoglobulin heavy and light chain loci, whereby the ordinary artisan could have pursued the known potential options with a reasonable expectation of success, as the antibody transgenes were successfully demonstrated by the cited prior art to be expressed from genetically modified B cells via genomic integration using both options, and the number of potential options from which to choose is neither astronomical nor insurmountable, and given the guidance of the cited prior art, it would only be routine experimentation to integrate the artisan’s therapeutic antibody heavy and light chain genes into the endogenous immunoglobulin heavy and light chain genes.
Those of ordinary skill in the art previously recognized and/or successfully reduced to practice that gene editing technologies such as ZFN nucleases and CRISPR/Cas9 system are able to edit the genome of human immune cells, including T and B cells, including primary human immune cells. Thus, it is considered that those of ordinary skill in the art would have a reasonable expectation of success for gene editing technologies such as ZFN nucleases and CRISPR/Cas9 system to edit the genome of primary human B cells, there being no objective evidence of undue experimentation in the art.
It is proper to "take account of the inferences and creative steps that a person of ordinary skill in the art would employ." KSR Int'l Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741,82 USPQ2d 1385, 1396 (2007). See also Id. At 1742, 82 USPQ2d 1397 ("A person of ordinary skill is also a person of ordinary creativity, not an automaton.").
It should be noted that the KSR case forecloses the argument that a specific teaching, suggestion, or motivation is required to support a finding of obviousness. See the recent Board decision Ex parte Smith, —USPQ2d—, slip op. at 20, (Bd. Pat. App. & Interf. June 25, 2007) (citing KSR, 82 USPQ2d at 1396) (available at http: www. uspto.gov/web/offices/dcom/bpai/prec/fd071925 .pdf).
With respect to Claim 34, Scholz et al disclosed wherein the genetically modified primary human B cells of the population secrete a defined therapeutic antibody encoded by the inserted sequences (e.g. [0018], “develop into plasma cells (activated B cells) that secrete abundant amounts of the protein encoded by the nucleic acid of interest”; [0031], “B cell into an antibody secreting cell”; Example 1, [0128], “able to differentiate the [genetically] modified quiescent B cell into a plasma cells”; Figure 1, b12 antibody production).
Hyde et al disclosed the artisan’s heterologous immunoglobulin heavy and light chain genes may be specific for influenza [0038], e.g. an anti-influenza broadly neutralizing antibody secreted from the B cell ([0042], “secreted anti-influenza broadly neutralizing antibodies”), or HCV (e.g. [0082], the replacement Ig genes…encode a secreted anti-HCV antibody), or S. aureus pathogen (e.g. Example 5, [0111], anti-S. aureus PNAG antibody, [0107], secreted immunoglobulins to methicillin-resistant S. aureus (MRSA)).
With respect to Claim 41, Buelow et al disclosed a population of somatic cells in which a human immunoglobulin locus transgene is either randomly inserted in the host B cell genome ([0112], as per Scholz et al) or replaces the endogenous immunoglobulin locus, e.g. via homologous recombination (e.g. [0113]), wherein the transgenic immunoglobulin locus encodes an immunoglobulin heavy chain or an immunoglobulin light chain (e.g. 0107]), which necessarily reads upon one or more of the endogenous heavy or light chain loci selected from the group consisting of IGHV, IGHD, IGHJ, IGKV, and IGKJ.
Hyde et al disclosed a population of B cells isolated from an individual ([0037], “isolating human B cells from an individual”), whereby the endogenous immunoglobulin heavy and light genes encoding a B cell receptor are deleted, being replaced via homologous recombination with a heterologous nucleic acid encoding the artisan’s immunoglobulin heavy and light chain genes [0037, 73], which necessarily reads upon one or more of the endogenous heavy or light chain loci selected from the group consisting of IGHV, IGHD, IGHJ, IGKV, and IGKJ.
With respect to Claim 42, Scholz et al disclosed wherein the monoclonal antibody is specific for HIV-1 (e.g. [0076, 87], b12 anti-HIV-1 neutralizing antibody; Example 1, primary human B cells transduced to successfully produce the HIV neutralizing antibody b12).
Hyde et al disclosed the artisan’s heterologous immunoglobulin heavy and light chain genes may be specific for influenza [0038], e.g. an anti-influenza broadly neutralizing antibody secreted from the B cell ([0042], “secreted anti-influenza broadly neutralizing antibodies”), or HCV (e.g. [0082], the replacement Ig genes…encode a secreted anti-HCV antibody), or S. aureus pathogen (e.g. Example 5, [0111], anti-S. aureus PNAG antibody, [0107], secreted immunoglobulins to methicillin-resistant S. aureus (MRSA)).
With respect to Claim 43, the claim fails to further limit the independent claim. See above 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, rejection.
To the extent Applicant argues otherwise, see above 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, and 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, rejections.
With respect to Claim 44, the claim fails to further limit the independent claim. See above 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, rejection.
To the extent Applicant argues otherwise, see above 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, rejection.
With respect to Claim 45, the claim fails to further limit the independent claim. See above 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, rejection.
To the extent Applicant argues otherwise, see above 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, rejection.
With respect to Claim 46, the claim fails to further limit the independent claim. See above 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, rejection.
To the extent Applicant argues otherwise, see above 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, and 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, rejections.
With respect to Claim 47, the claim fails to further limit the independent claim. See above 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, rejection.
With respect to Claim 48(i), the claim fails to further limit the independent claim. See above 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, rejection.
To the extent Applicant argues otherwise, see above 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, and 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, rejections.
The cited prior art meets the criteria set forth in both Graham and KSR, and the teachings of the cited prior art provide the requisite teachings and motivations with a clear, reasonable expectation of success. Thus, the invention as a whole is prima facie obvious.
19. Claims 42 and 48 are rejected under AIA 35 U.S.C. 103 as being unpatentable over Scholz et al (U.S. 2013/0143267; of record) in view of Buelow et al (U.S. 2007/0033661; of record), Hyde et al (U.S. 2013/0164277; of record), Ando et al (U.S. 2008/0159996; of record), Wang et al (available online August 25, 2014; of record), and Mandal et al (available online November 6, 2014; of record cited), as applied to Claims 23, 34, 36, and 41-48 above, and in further view of Fang et al (Stable antibody expression at therapeutic levels using the 2A peptide, Nature Biotechnol. 23(5): 584-590, 2005).
Determining the scope and contents of the prior art, and Ascertaining the differences between the prior art and the claims at issue.
With respect to Claim 42, Hyde et al disclosed an antibody specific for influenza, hepatitis C, Staphylococcus aureus (e.g. [0042, 112]; Examples 2 and 6).
Beulow et al disclosed wherein the antibody is specific for Staphylococcus aureus, RSV, HCV, HBV, CMV, HSV, HER2, CD19, CD20, and CD22 (e.g. [0123-126]).
Neither Hyde et al, Ando et al, Buelow et al, Wang et al, nor Mandal et al teach/disclose wherein the antibody further comprises an epitope tag.
However, prior to the effective filing date of the instantly claimed invention, and with respect to Claim(s) 42 and 48(iii), Fang et al is considered relevant prior art for having taught mammalian antibody producer cells transfected with nucleic acids encoding light and heavy chains of a monoclonal antibody specific for VEGFR2 (entire paper; e.g. pg 584, col. 2), wherein the C-terminus of the antibody light chain is modified to comprise an epitope tag (e.g. pg 585, col. 2, “his-tag”).
Considering objective evidence present in the application indicating obviousness or nonobviousness.
The focus when making a determination of obviousness should be on what a person of ordinary skill in the pertinent art would have known at the time of the invention, and on what such a person would have reasonably expected to have been able to do in view of that knowledge. This is so regardless of whether the source of that knowledge and ability was documentary prior art, general knowledge in the art, or common sense. M.P.E.P. §2141.
The rationale to modify or combine the prior art does not have to be expressly stated in the prior art; the rationale may be expressly or impliedly contained in the prior art or it may be reasoned from knowledge generally available to one of ordinary skill in the art, established scientific principles, or legal precedent established by prior case law. 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). See also In re Kotzab, 217 F.3d 1365, 1370, 55 USPQ2d 1313, 1317 (Fed. Cir. 2000) (setting forth test for implicit teachings); In re Eli Lilly & Co., 902 F.2d 943, 14 USPQ2d 1741 (Fed. Cir. 1990) (discussion of reliance on legal precedent); In re Nilssen, 851 F.2d 1401, 1403, 7 USPQ2d 1500, 1502 (Fed. Cir. 1988) (references do not have to explicitly suggest combining teachings); and Ex parte Levengood, 28 USPQ2d 1300 (Bd. Pat. App. & Inter. 1993) (reliance on logic and sound scientific reasoning). See MPEP §2144.
Prior to the effective filing date of the instantly claimed invention, it would have been obvious to one of ordinary skill in the art to substitute a first monoclonal antibody-encoding nucleic acid, as disclosed by Hyde et al and Buelow et al, with a second monoclonal antibody-encoding nucleic acid, to wit, an anti-VEGFR2 monoclonal antibody-encoding nucleic acid, as taught by Fang et al, in primary human B antibody producer cells with a reasonable expectation of success because the simple substitution of one known element for another would have yielded predictable results to one of ordinary skill in the art at the time of the invention. M.P.E.P. §2144.07 states "The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945).” “Reading a list and selecting a known compound to meet known requirements is no more ingenious than selecting the last piece to put in the last opening in a jig-saw puzzle." 325 U.S. at 335, 65 USPQ at 301.).” When substituting equivalents known in the prior art for the same purpose, an express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982). M.P.E.P. §2144.06. An artisan would be motivated to substitute a first monoclonal antibody-encoding nucleic acid with a second monoclonal antibody-encoding nucleic acid, to wit, an anti-VEGFR2 monoclonal antibody-encoding nucleic acid, in primary human B antibody producer cells because those of ordinary skill in the art had long-recognized that recombinant anti-VEGFR2 monoclonal antibodies are produced in mammalian producer cells, and the genomic modifications to primary human B cells to produce therapeutic monoclonal antibodies is not restrictive to the target molecule that is to be recognized by the monoclonal antibody.
Prior to the effective filing date of the instantly claimed invention, it also would have been obvious to one of ordinary skill in the art to modify the heterologous light and/or heavy chain variable regions to comprise an epitope tag with a reasonable expectation of success because those of ordinary skill in the art previously recognized the scientific and technical concepts of appending their protein of interest, including an antibody (Fang et al) to further comprise an epitope tag.
The specification discloses using the epitope tag to detect expression of the heterologous protein of interest (e.g. [00046], “shows FLAG expression”, “HA expression”; [000200], “tags to facilitate purification, detection”).
The purpose of modifying the artisan’s protein of interest to comprise an epitope tag is to allow the ordinary artisan to detect expression of and/or purify said protein of interest, as successfully demonstrated by Fang et al (e.g. pg 589, col. 1, Methods, His-tagged antibody expression).
It is proper to "take account of the inferences and creative steps that a person of ordinary skill in the art would employ." KSR Int'l Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741,82 USPQ2d 1385, 1396 (2007). See also Id. At 1742, 82 USPQ2d 1397 ("A person of ordinary skill is also a person of ordinary creativity, not an automaton.").
It should be noted that the KSR case forecloses the argument that a specific teaching, suggestion, or motivation is required to support a finding of obviousness. See the recent Board decision Ex parte Smith, —USPQ2d—, slip op. at 20, (Bd. Pat. App. & Interf. June 25, 2007) (citing KSR, 82 USPQ2d at 1396) (available at http: www. uspto.gov/web/offices/dcom/bpai/prec/fd071925 .pdf).
The cited prior art meets the criteria set forth in both Graham and KSR, and the teachings of the cited prior art provide the requisite teachings and motivations with a clear, reasonable expectation of success. Thus, the invention as a whole is prima facie obvious.
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 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); 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 nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
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20. Claims 23, 34, 36, and 41-48 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 53, 57, 60, 64, 66-67, and 69-71 of copending Application No. 18/141278 (reference application; claim set filed April 22, 2026).
Although the claims at issue are not identical, they are not patentably distinct from each other.
‘278 recites primary human B cells whose genomes have been modified with insertion of heterologous nucleic acids encoding heavy and light chains of a therapeutic monoclonal antibody, each of which comprise at least the respective heavy and light chain variable regions. ‘278 claims do not exclude the presence of other heavy and light chain domains present in the instantly claimed antibodies.
With respect to the newly introduced limitation wherein the cells of the population lack exogenous viral nucleic acids, and in light of Applicant’s remarks indicating that this negative limitation refers to the donor template introduced into the endogenous heavy or light chain gene,
Buelow et al disclosed a population of somatic cells in which a human immunoglobulin locus transgene replaces the endogenous immunoglobulin locus, e.g. via homologous recombination (e.g. [0112-113]). There is no objective evidence that the genome-edited primary human B cells of Buelow et al in which the endogenous heavy or light chain locus is genome-edited with a heterologous immunoglobulin locus transgene comprises exogenous viral nucleic acids.
Hyde et al disclosed a population of B cells isolated from an individual ([0037], “isolating human B cells from an individual”), whereby the endogenous immunoglobulin heavy and light genes encoding a B cell receptor are deleted, being replaced via homologous recombination with a heterologous nucleic acid encoding the artisan’s immunoglobulin heavy and light chain genes [0037, 73]. There is no objective evidence that the genome-edited primary human B cells of Hyde et al in which the endogenous heavy or light chain locus is genome-edited with a heterologous immunoglobulin locus transgene comprises exogenous viral nucleic acids.
With respect to Claim 43, the claim fails to further limit the independent claim. See above 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, rejection.
To the extent Applicant argues otherwise, see above 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, and 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, rejections.
With respect to Claim 44, the claim fails to further limit the independent claim. See above 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, rejection.
To the extent Applicant argues otherwise, see above 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, rejection.
With respect to Claim 45, the claim fails to further limit the independent claim. See above 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, rejection.
To the extent Applicant argues otherwise, see above 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, rejection.
With respect to Claim 46, the claim fails to further limit the independent claim. See above 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, rejection.
To the extent Applicant argues otherwise, see above 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, and 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, rejections.
With respect to Claim 47, the claim fails to further limit the independent claim. See above 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, rejection.
With respect to Claim 48(i), the claim fails to further limit the independent claim. See above 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, rejection.
To the extent Applicant argues otherwise, see above 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, and 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, rejections.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Citation of Relevant Prior Art
21. The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Li et al (Optimization of Genome Engineering Approaches with the CRISPR/Cas9 System, PLoS One 9(8): e105779; 10 pages, available online August 28, 2014; of record) is considered relevant prior art for having taught optimization of the CRISPR/Cas9 system for genome engineering (Title), wherein said optimization includes comparison of different guide RNA target sequences, individually or in combination, e.g. GFP KO gRNAs (Table 1; pg 3, col. 2), as such is common practice in the art (See also citation #13 to Mali et al, “target specificity screening”). Li et al taught that the cleavage efficiency “varied based on the transfection efficiency” (pg 3, col. 2).
Schumann et al (Generation of knock-in primary human T cells using Cas9 ribonucleoproteins, Proc. Nat’l Acad. Sci. 112(33): 10437-10442, available online July 27, 2015; of record in IDS of parent application 16/152,273) is considered relevant prior art for having taught that the editing efficiency of a Cas9/gRNA ribonucleoprotein complex delivered in vitro into primary human T cells, whereby editing efficiency varies depending upon the dose of the Cas9/gRNA RNP concentration (pg 10438, col. 2; Figure 4d).
Liang et al (Rapid and highly efficient mammalian cell engineering via Cas9 protein transfection, J. Biotechnol. 208: 44-53, May 21, 2015; of record) is considered relevant prior art for having taught that the indel efficiency of a Cas9 protein/gRNA RNP complex varies widely, depending upon the electroporation conditions (Figure 4a). Liang et al taught that % error rates (syn. off-target) varies, between 1 off-targets to as many as 20 off-targets, with the overall structure of the gRNA molecule, including the tracrRNA and 3’ end(s) (e.g. Figure 2). Similarly, the off-target rates can also vary according to the concentration of the Cas9 protein present in the Cas9/gRNA RNP (e.g. pg 49, col. 2).
Briner et al (Guide RNA Functional Modules Direct Cas9 Activity and Orthogonality Molecular Cell 56: 333-339, October 23, 2014; of record) is considered relevant prior art for having taught that changes to the nucleotide sequence(s) and length(s) of the gRNA molecule affects the ability of the gRNA to bind to different Cas9 orthologs, subsequently affecting the ability of the gRNA variants/Cas9 ortholog variants to efficiently cleave the intended target site nucleotide sequence (e.g. Figure 1). Briner et al taught that, “the molecular basis of selective Cas9:guide-RNA interactions is poorly understood” (Abstract). Distinct portions of the sgRNA are predicted to form various features that interact with Cas9 and/or the DNA target. However, the boundaries and respective roles of these portions remain to be determined (pgs 333-334, joining para.).
Bovia et al (Efficient transduction of primary human B lymphocytes and nondividing myeloma B cells with HIV-1–derived lentiviral vectors, Blood 101(5): 1727-1733, 2003; of record in prior application 15/161,213) is considered relevant prior art for having taught the ability of the ordinary artisan to efficiently transduce primary human B cells with a transgene of interest.
Frecha et al (Mol. Therapy 18(10): 1748-1757, 2010; of record in prior application 15/161,213) is considered relevant prior art for having taught a novel lentiviral psuedotype vector that allows the ordinary artisan to transduce the artisan’s gene of interest into quiescent primary human B cells.
Coughlin et al (Cancer Biol. & Therapy 2(5): 466-470, 2003; of record in prior application 15/161,213) is considered relevant prior art for having taught the genetic modification of a human patient’s primary B cells as a cell-based approach to treat human disease.
Buelow (U.S. Patent 8,907,157; priority to June 1, 2007; of record in prior application 15/161,213) is considered relevant prior art for having disclosed site-specific meganucleases to insert an exogenous nucleic acid encoding an antibody into an endogenous immunoglobulin locus, thereby replacing all or a portion of the endogenous immunoglobulin locus (col. 4, lines 43-46; col. 8, lines 36-50; col. 12, lines 15-16, “the insertion sequence is an artificial Ig locus and replaces an endogenous Ig locus”).
Maier et al (Efficient Clinical Scale Gene Modification via Zinc Finger Nuclease–Targeted Disruption of the HIV Co-receptor CCR5, Human Gene Therapy 24: 245-258, 2013; of record) is considered relevant prior art for having taught the use of an adenoviral vector to deliver ZFNs into primary human T cells, thereby editing the genome of said primary human T cells.
Maier et al cite Jung et al (Efficient gene transfer into normal human B lymphocytes with the chimeric adenoviral vector AD5/F35, J. Immunol. Methods 304(Issues 1-2): 78-87, 2005; of record) for having taught that the adenoviral vector was previously recognized in the art to successfully transduce the artisan’s nucleic acids of interest into primary human B lymphocytes.
Thus, prior to the effective filing date of the instantly claimed invention, those of ordinary skill in the art would have had a reasonable expectation of success for the ability to edit the genome of primary human B cells because the prior art recognized and had successfully reduced to practice the use of nucleic acid delivery vehicles to transduce primary human B cells.
Conclusion
22. No claims are allowed.
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 nonprovisional extension fee (37 CFR 1.17(a)) 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 mailing date of this final action.
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KEVIN K. HILL
Examiner
Art Unit 1638
/KEVIN K HILL/Primary Examiner, Art Unit 1638
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