DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 19, 20, 22-25 have been canceled. Claims 1-18, 21 are pending.
Election/Restrictions
Applicant’s election of Group I, claims 1-9, in the reply filed on 10-8-25 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 10-18, 21 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 10-8-25.
Claim Interpretation
It is assumed the metes and bounds of “non-obese diabetic (NOD)” mice in claim 1 were well-known.
It is assumed the metes and bounds of NOD mice that are “Prkdcscid” and IL2rgtm1Wjl” in claim 2 were well-known.
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.
Written description
Claims 1-9 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.
A) The specification lacks written description for a mouse having the alleles and nucleic acids as broadly claimed other than a genetically modified mouse whose genome comprises i) an inactivated Prkdc allele, ii) an inactivated IL2rg allele, iii) an inactivated Flt3 allele, iv) a nucleic acid sequence encoding human IL3, v) a nucleic acid sequence encoding human GM-CSF, vi) a nucleic acid sequence encoding human SCF, and vii) a nucleic acid sequence encoding HLA-A2/H2-D/B2M, wherein the mouse does not express functional PRKDC, IL2rg, or Flt3 and functionally expresses human IL3, human GM-CSF, human SCF, and HLA-A2/H2-D/B2M.
Claim 1 is drawn to a non-obese diabetic (NOD) mouse comprising an inactivated mouse Prkdc allele;an inactivated mouse IL2rg allele; an inactivated mouse Flt3 allele; a nucleic acid encoding human interleukin 3 (IL3); a nucleic acid encoding human granulocyte/macrophage-stimulating factor (GM-CSF); a nucleic acid encoding human stem cell factor (SCF); and a nucleic acid encoding a human B2-microglubulin (B2M) covalently linked to MHC class 1, alpha2, and alpha2 binding domains of a human HLA-A2.1 gene, and alpha3 cytoplasmic and transmembrane domains of murine H2-Db (HLA-A2/H2-D/B2M).
The claim encompasses a mouse with naturally occurring inactivated Prkdc, IL2rg, or Flt3 alleles or a genetically modified mouse with the inactivated Prkdc, IL2rg, or Flt3 alleles. The claim encompasses a mouse with inactivated Prkdc, IL2rg, or Flt3 allele in one or more cell. Claim 1 does not require the genome of the mouse has an inactivated Prkdc, IL2rg, and Flt3 allele. The claim encompasses a mouse with one or more cell comprising nucleic acids encoding human IL3, GM-CSF, SCF and HLA-A2/H2-D/B2M. Claim 1 does not require the genome of the mouse has nucleic acids encoding human IL3, GM-CSF, SCF and HLA-A2/H2-D/B2M.
Claim 1 encompasses a mouse that expresses the human IL3, human GM-CSF, human SCF, and HLA-A2/H2-D/B2M as well as a mouse that does not.
Claim 1 encompasses a mouse with normal expression of Prkdc, IL2rg and Flt3, a mouse with decreased expression of Prkdc, IL2rg and Flt3, or a mouse that does not express Prkdc, IL2rg or Flt3.
However, the specification is limited to a genetically modified mouse whose genome comprises i) an inactivated Prkdc allele, ii) an inactivated IL2rg allele, iii) an inactivated Flt3 allele, iv) a nucleic acid sequence encoding human IL3, v) a nucleic acid sequence encoding human GM-CSF, vi) a nucleic acid sequence encoding human SCF, and vii) a nucleic acid sequence encoding HLA-A2/H2-D/B2M, wherein the mouse does not express functional PRKDC, IL2rg, or Flt3 and functionally expresses human IL3, human GM-CSF, human SCF, and HLA-A2/H2-D/B2M. The specification does not correlate a mouse whose genome comprises the genetic modification to a mouse with only one or a few cells with the genetic modification. Accordingly, the concept lacks written description other than a genetically modified mouse whose genome comprises i) an inactivated Prkdc allele, ii) an inactivated IL2rg allele, iii) an inactivated Flt3 allele, iv) a nucleic acid sequence encoding human IL3, v) a nucleic acid sequence encoding human GM-CSF, vi) a nucleic acid sequence encoding human SCF, and vii) a nucleic acid sequence encoding HLA-A2/H2-D/B2M, wherein the mouse does not express functional PRKDC, IL2rg, or Flt3 and functionally expresses human IL3, human GM-CSF, human SCF, and HLA-A2/H2-D/B2M.
B) The specification lacks written description for a nucleic acid encoding a human B2-microglubulin (B2M) covalently linked to MHC class 1, alpha2, and alpha2 binding domains of a human HLA-A2.1 gene, and alpha3 cytoplasmic and transmembrane domains of murine H2-Db (HLA-A2/H2-D/B2M) as required in claim 1. The phrase mixes nucleic acid and amino acid language and appears to covalently link a nucleic acid to an HLA binding domain. While a nucleic acid encoding B2M may be operably linked to a nucleic acid encoding 1α and 2α binding domains of an HLA-A2, but it is not covalently linked to 1α and 2α binding domains of an HLA-A2 gene as claimed. Even the use of “MHC class 1, alpha2, and alpha2 binding domains of a human HLA-A2.1 gene” mixes proteins (the binding domains) with a nucleic acid (“an HLA-A2.1 gene”) which does not make sense. Accordingly, the phrase lacks written description.
C) The specification lacks written description for a “NOD.Cg-Prkdcscid IL2rgtm1Wjl/SzJ” mouse “comprising an inactivated mouse Flt3 allele; a nucleic acid encoding human IL3; a nucleic acid encoding human GM-CSF; a nucleic acid encoding human SCF; and a nucleic acid encoding HLA-A2/H2-D/B2M” as required in claim 2.
It is unclear how the phrase “comprising an inactivated Flt3 allele, a nucleic acid encoding human IL3…” in claim 2 further limits the mouse of claim 1 because the mouse already has those features in claim 1.
The metes and bounds of an “NOD.Cg-Prkdcscid IL2rgtm1Wjl/SzJ” mouse cannot be determined. Pg 3, line 9 uses the phrase but does not teach the structures/functions associated with the genetic modifications in the mouse or the metes and bound of what define when a NOD mouse is “Cg” or “SzJ”.
The phrase “NOD.Cg” is interpreted to mean the strain is “congenic”. Jackson Labs defines “congenic” as “An inbred strain of mouse that contains a small genetic region (ideally a single gene) from another strain, but which is otherwise identical to the original inbred strain. Congenic strains are derived by backcrossing to a parental inbred strain for at least ten generations while selecting for heterozygosity at a particular locus. A.BY-H2b H2-T18b/SnJ is a congenic strain.” The specification and the art at the time of filing do not define a NOD congenic background because the specification does not teach the structure of the “small genetic region” that was “selected for”, which strain it came from, which strain was used for backcrossing, or how many backcrosses were performed to obtain the desired structure/phenotype of a “NOD.Cg” background. The specification does not correlate well-known NOD mice to “NOD.Cg” mice.
Furthermore, the designation “Szj” refers to the lab in which the strain exists. The specification does describe how the structure of the NOD.Cg-Prkdcskid IL-2rgtm1Wjl/Szj strain differs from the NOD.Cg-Prkdcskid IL-2rgtm1Wjl/J, RI, or Kyo strains. “Genetic drift” occurs within each strain (Jackson Labs description of Genetic Drift, 2022); however, the specification does not describe or define the structure of a Szj strain or compare that structure to J, RI, or Kyo strains. The specification taken with the art at the time of filing does not provide adequate guidance for the structures that define or describe a NOD.Cg-Prkdcskid IL-2rgtm1Wjl mouse that is of the “Szj” strain or when it is no longer an Szj strain. The scope is uncertain because “Szj” is used to identify the source of the mouse and not the structure/function of the mouse itself.
Next, applicants indicate the nomenclature used in claim 2 refers to a NOD.Cg-Prkdcskid IL-2rgtm1Wjl/Szj strain is equivalent to claiming a mouse of the NSGTM strain (pg 3, line 9). However, the phrases “NOD.Cg-Prkdcskid IL-2rgtm1Wjl/Szj” and “NSGTM” cannot be used properly to identify the structure/function of the mouse because it is a Trademarked concept used to identify a source of goods, and not the structure/function of the goods themselves. The specification does not describe the structure/function of a “NOD.Cg-Prkdcskid IL-2rgtm1Wjl/Szj” or “NSGTM” mouse. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the phrase “NOD.Cg-Prkdcskid IL-2rgtm1Wjl/Szj” and the trademark “NSGTM” cannot be used properly to describe the structure/function associated with the terms “NOD.Cg” and “Szj”.
D) The specification lacks written description for a mouse expressing a detectable level of any HLA-A2 as required in claim 5 because it does not have a nexus with a mouse comprising a nucleic acid encoding HLA-A2/H2-D/B2M in claim 1. The concept in claim 5 is broader than the nucleic acid encoding HLA-A2/H2-D/B2M in claim 1 because it encompasses a nucleic acid encoding a fully human HLA-A2 including the cytoplasmic and transmembrane domains. But claim 1 says the 3α cytoplasmic and transmembrane domains are endogenous H2-Db, so the mouse cannot express fully human HLA-A2 as encompassed by claim 5. Accordingly, claim 5 appears broader than claim 1 and lacks written description.
E) The specification lacks written description for CD45+ hematopoietic progenitors that are CD19+ B-cells, CD33+ myeloid cells, and CD3+ T-cells as required in claim 7. B-cells, myeloid cells and T-cells are differentiated; they are not progenitors as claimed. Perhaps CD19+ B-cells, CD33+ myeloid cells, and CD3+ T-cells can express CD45, but they are not progenitors as claimed. Therefore, the concept lacks written description.
F) The specification lacks written description for transplanting human CD45+ hematopoietic progenitor cells, wherein “lung tissue of the mouse comprises CD3+ T-cells and HLA-DR+CD11c+ dendritic cells” as required in claim 8. Pg 10, lines 19-30, discuss “NSG-SGM3F-A2” mice with increased CD11C+ HLA-DR+ myeloid dendritic cells as compared to an NSGTM or NSGF mouse. The specification does not teach they are in the lung as required in claim 8. Therefore, the concept lacks written description.
G) The specification lacks written for any mouse that has HLA-A2+ thymic epithelial cells as broadly encompassed by claim 9. The claim encompasses a mouse in which HLA-A2 is specifically expressed only in thymic epithelial cells as well as a mouse in which HLA-A2 is ubiquitously expressed. The specification is limited to a transgenic mouse whose genome comprises a nucleic acid sequence encoding HLA-A2/H2D/B2M, wherein the mouse ubiquitously expresses the HLA-A2/H2D/B2M. The specification does not correlate ubiquitous presence of the nucleic acid encoding HLA-A2/H2D/B2M to tissue-specific presence of the nucleic acid only in thymic epithelial cells as broadly encompassed by claim 9. The specification does not correlate ubiquitous expression of HLA-A2/H2D/B2M to tissue-specific expression only in thymic epithelial cells as broadly encompassed by claim 9. Accordingly, the concept lacks written description.
Indefiniteness
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.
Claims 1-9 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
A) The specification concept of “a nucleic acid encoding a human B2-microglubulin (B2M) covalently linked to MHC class 1, alpha2, and alpha2 binding domains of a human HLA-A2.1 gene, and alpha3 cytoplasmic and transmembrane domains of murine H2-Db (HLA-A2/H2-D/B2M)” in claim 1 can makes the claim indefinite. The phrase mixes nucleic acid and amino acid language and appears to covalently link a nucleic acid to an HLA binding domain; this concept is not within the realm of science, logic, or legal clarity. While a nucleic acid encoding B2M may be operably linked to a nucleic acid encoding 1α and 2α binding domains of an HLA-A2, but it is not covalently linked to 1α and 2α binding domains of an HLA-A2 gene as claimed. The phrase “MHC class 1, alpha2, and alpha2 binding domains of a human HLA-A2.1 gene” also mixes proteins (the binding domains) with a nucleic acid (“an HLA-A2.1 gene”) which does not make sense. Accordingly, those of skill would not be able to determine when they were infringing on the claim.
B) The phrase “NOD.Cg-Prkdcscid IL2rgtm1Wjl/SzJ” mouse “comprising an inactivated mouse Flt3 allele; a nucleic acid encoding human IL3; a nucleic acid encoding human GM-CSF; a nucleic acid encoding human SCF; and a nucleic acid encoding HLA-A2/H2-D/B2M” in claim 2 makes the claim indefinite.
First, it is unclear how the phrase “comprising an inactivated Flt3 allele, a nucleic acid encoding human IL3…” in claim 2 further limits the mouse of claim 1 because the mouse already has those features in claim 1.
Second, the metes and bounds of an “NOD.Cg-Prkdcscid IL2rgtm1Wjl/SzJ” mouse cannot be determined. Pg 3, line 9 uses the phrase but does not teach the structures/functions associated with the genetic modifications in the mouse or the metes and bound of what define when a NOD mouse is “Cg” or “SzJ”.
The phrase “NOD.Cg” is interpreted to mean the strain is “congenic”. Jackson Labs defines “congenic” as “An inbred strain of mouse that contains a small genetic region (ideally a single gene) from another strain, but which is otherwise identical to the original inbred strain. Congenic strains are derived by backcrossing to a parental inbred strain for at least ten generations while selecting for heterozygosity at a particular locus. A.BY-H2b H2-T18b/SnJ is a congenic strain.” The specification and the art at the time of filing do not define a NOD congenic background because the specification does not teach the structure of the “small genetic region” that was “selected for”, which strain it came from, which strain was used for backcrossing, or how many backcrosses were performed to obtain the desired structure/phenotype of a “NOD.Cg” background. The specification does not correlate well-known NOD mice to “NOD.Cg” mice.
Furthermore, the designation “Szj” refers to the lab in which the strain exists. The specification does describe how the structure of the NOD.Cg-Prkdcskid IL-2rgtm1Wjl/Szj strain differs from the NOD.Cg-Prkdcskid IL-2rgtm1Wjl/J, RI, or Kyo strains. “Genetic drift” occurs within each strain (Jackson Labs description of Genetic Drift, 2022); however, the specification does not describe or define the structure of a Szj strain or compare that structure to J, RI, or Kyo strains. The specification taken with the art at the time of filing does not provide adequate guidance for the structures that define or describe a NOD.Cg-Prkdcskid IL-2rgtm1Wjl mouse that is of the “Szj” strain or when it is no longer an Szj strain. The scope is uncertain because “Szj” is used to identify the source of the mouse and not the structure/function of the mouse itself.
Next, applicants indicate the nomenclature used in claim 2 refers to a NOD.Cg-Prkdcskid IL-2rgtm1Wjl/Szj strain is equivalent to claiming a mouse of the NSGTM strain (pg 3, line 9). However, the phrases “NOD.Cg-Prkdcskid IL-2rgtm1Wjl/Szj” and “NSGTM” cannot be used properly to identify the structure/function of the mouse because it is a Trademarked concept used to identify a source of goods, and not the structure/function of the goods themselves. The specification does not describe the structure/function of a “NOD.Cg-Prkdcskid IL-2rgtm1Wjl/Szj” or “NSGTM” mouse. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the phrase “NOD.Cg-Prkdcskid IL-2rgtm1Wjl/Szj” and the trademark “NSGTM” cannot be used properly to describe the structure/function associated with the terms “NOD.Cg” and “Szj”. Accordingly, those of skill would not be able to determine when they were infringing on the claim.
C) The concept of a nucleic acid encoding HLA-A2/H2-D/B2M being a “transgene” in claim 3 does not further limit the structure/function of the mouse in claim 1 or the nucleic acid encoding HLA-A2/H2-D/B2M in claim 1. The nucleic acid encoding HLA-A2/H2-D/B2M in claim 1 encodes a human protein, so it cannot naturally exist in the mouse. The only way to express a human protein in a mouse is via a transgene, so the nucleic acid encoding HLA-A2/H2-D/B2M in claim 1 inherently MUST be a transgene. Therefore, claim 3 does not further limit claim 1.
If applicants are attempting to say the term “transgene” somehow further limits the structure/function of the nucleic acid encoding HLA-A2/H2-D/B2M, then it is wholly unclear what structures/functions are associated with a transgene encoding HLA-A2/H2-D/B2M in claim 5 that are not implicit from a nucleic acid encoding a human protein in a mouse. If “transgene” DOES further limit claim 1, then those of skill would not be able to determine when they were infringing on the claim.
D) The concept of the mouse expressing a detectable level of any HLA-A2 as required in claim 5 does not have a nexus with a mouse comprising a nucleic acid encoding HLA-A2/H2-D/B2M in claim 1. This makes the claim indefinite. The concept in claim 5 is broader than the nucleic acid encoding HLA-A2/H2-D/B2M in claim 1 because it encompasses a nucleic acid encoding a fully human HLA-A2 including the cytoplasmic and transmembrane domains. But claim 1 says the 3α cytoplasmic and transmembrane domains are endogenous H2-Db, so the mouse cannot express fully human HLA-A2 as encompassed by claim 5. Accordingly, claim 5 appears broader than claim 1 which makes the claim indefinite.
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 (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-5 are rejected under 35 U.S.C. 103 as being unpatentable over Shultz (Mammalian Genome, 2019, Vol. 30, pg 123-142).
Shultz taught SGM3F mice (NOD.Cg-Prkdcscid Il2rg -Flt3 (CMV-IL3, CSF, KITLG)) (pg 126, Table 1, items 10 and 11) and HLA-A0201 transgenic mice (NSG-HLA-A2 (HHD)) (pg 127, Table 1, item 5).
Shultz did not teach crossing SGM3F mice with HLA-A0201 as described by applicants on pg 14, lines 1-10.
However, Shultz taught both types of mice and taught crossing SGM3F mice with other mice, i.e. NSG-Tg(CSF1) mice (pg 130, col. 1, last para).
Thus, it would have been obvious to those of ordinary skill in the art at the time of filing to cross the SGM3F mouse as described by Shultz using the HLA-A0201 mouse of Shultz. Those of ordinary skill in the art at the time of filing would have been motivated to do so to impart expression of human HLA-A0201 in the mouse thereby making it even more humanized. In the reverse, those of ordinary skill in the art at the time of filing would have been motivated to express human IL3, CSF, and GM-CSF in the HLA-A0201 mouse for immune response research.
Claim 2 has been included because the mouse resulting from the cross is “NOD.Cg-Prkdcscid Il2rg tm1Wjl/SzJ (NOD scid gamma), has an inactivated FLT3 gene, expresses human IL3, human GM-CSF, human SCF and HLA-A2/H2-D/B2M and because they are the same mice crossed by applicants (pg 14, lines 1-10).
Claim 3 has been included because the HLA-A2 mouse of Shultz is the same mouse used by applicants and expresses HLA-A2/H2-D/B2M (pg 14, lines 1-10).
Claim 4 has been included because the HLA-A2 mouse of Shultz is the same mouse used by applicants and expresses HLA-A2/H2-D/B2M (pg 14, lines 1-10).
The bone marrow cells of the mouse inherently MUST express CD45 by the age of 4 weeks as required in claim 5 because they are obtained by crossing the same mice used by applicants (pg 14, lines 1-10).
Thus, Applicants' claimed invention as a whole is prima facie obvious in the absence of evidence to the contrary.
Claims 6-9 are rejected under 35 U.S.C. 103 as being unpatentable over Shultz (Mammalian Genome, 2019, Vol. 30, pg 123-142) as applied to claims 1-5 above, and further in view of Matsumura (Exp. Hematology, 2003, Vol. 31, No. 9, pg 789-797), Traggiai (Science, 2004, Vol. 304, No. 5667, pg 104-107), Aspord (J. Exp. Med, 2007, Vol. 204, No. 5, pg 1037-1047), Pedroza-Gonzalez (J. Exp. Med., 2011, Vol. 208, No. 3, pg 479-490), Wu (Cancer Immunol. Res., 2014, Vol. 2, No. 5, pg 487-500), Wu (Cancer Res., 2018, Vol. 78, No. 18, pg 5243-5258), and Yu (Blood, 2008, Vol. 112, No. 9, pg 3671-3678).
Shultz obviated the mouse of claim 1 for reasons set forth above.
Shultz did not teach administering human HPCs to the mouse as required in claim 6.
However, it was well-known to irradiate a humanized mouse and administer human CD45+ HPCs to humanized mice as described by Matsumura, Traggiai, Aspord, Pedroza-Gonzalez, Wu, Wu, and Yu (see materials and methods for each). Applicants acknowledge their contribution to administering human HPCs on pg 1, lines 17-25, of the specification.
Thus, it would have been obvious to those of ordinary skill in the art at the time of filing to obtain the mouse of claim 1 by crossing the SGM3F and HLA-A0201 mice described by Shultz and administer human HPCs as described by Matsumura, Traggiai, Aspord, Pedroza-Gonzalez, Wu, Wu, and Yu. Those of ordinary skill in the art at the time of filing would have been motivated to administer HPCs to make the mice more humanized, especially when the mouse has been given a human tumor.
Claim 7 has been included because Matsumura, Traggiai, Aspord, Pedroza-Gonzalez, Wu, Wu, and Yu taught the HPCs were obtained from fetal liver, cord blood, or bone marrow and comprise a mixed population of CD19+ B-cells, CD33+ myeloid cells, and CD3+ T-cells.
Claim 8 has been included because Matsumura, Traggiai, Aspord, Pedroza-Gonzalez, Wu, Wu, and Yu taught the HPCs were obtained from fetal liver, cord blood, or bone marrow and comprise CD3+ T-cells and HLA-DR+CD11c+ dendritic cells.
Claim 9 has been included because Matsumura, Traggiai, Aspord, Pedroza-Gonzalez, Wu, Wu, and Yu taught the HPCs were HLA-A2+. The thymic epithelial cells of the mouse are HLA-A2+ because they were obtained from HLA-A0201 mice.
Thus, Applicants' claimed invention as a whole is prima facie obvious in the absence of evidence to the contrary.
Conclusion
No claim is allowed.
Inquiry concerning this communication or earlier communications from the examiner should be directed to Michael C. Wilson who can normally be reached at the office on Monday through Friday from 9:30 am to 6:00 pm at 571-272-0738.
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Michael C. Wilson
/MICHAEL C WILSON/
Primary Examiner, Art Unit 1638