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
The Response of 16 March 2026 has been entered.
Claims 1-17 are currently pending. Claims 7-14 and 17 are withdrawn as being drawn to a nonelected invention. Claims 1-6, 15 and 16 are considered here with respect to the elected species of: HOXB8 as the homeobox gene and a method for determining whether a patient is allergic to an allergen and/or the severity of an allergy to an allergen as the method.
Any rejection not reiterated herein has been withdrawn.
Response to Arguments
Applicant's arguments filed 13 March 2026 have been fully considered but they are not persuasive.
Regarding the new matter rejection, Applicant argues that the specification describes a culture method for differentiating progenitors into mature mast cells after culturing for multiple days, and that one of ordinary skill in the art would recognize that such "mature" cells are terminally differentiated. This is not persuasive because the term "terminally differentiated" has a specific meaning in the art, i.e. incapable of further proliferation. As evidenced by Kitamura et al., Bioessays 10.6 (1989): 193-196, some mature mast cells retain a proliferative potential and thus cannot be considered "terminally differentiated" (p. 193, last ¶ to p. 194, 1st ¶). Thus, the description of "mature" mast cells in the specification does not inherently mean such cells are terminally differentiated.
Regarding the 103 rejection, Applicant argues that Kampf teaches a method for progenitor cell immobilization but does not teach modification of the genetic background of the donor animal nor the use of transgenic animals expressing a high affinity IgE receptor. Applicant further argues that while Fung-Leung teaches mast cells expressing human high affinity IgE receptor, it does not teach immortalized progenitor cells. Applicant's arguments are not persuasive because one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Kampf teaches a method of producing conditionally immortalized mast cell progenitors by introducing a recombinant inducible HoxB8 gene into bone marrow progenitor cells derived from a non-human animal, and further teaches that the progenitor cells can be isolated from a transgenic animal such as a transgenic mouse comprising a transgene useful in studying an inflammatory response. Fung-Leung teaches mast cells isolated from a transgenic mouse expressing a heterologous human high-affinity IgE receptor alpha subunit, which provides an animal model for the study of human IgE in allergic reactions. Since Kampf specifically teaches that the mast cell progenitors can be isolated from a transgenic animal, it would have been obvious to apply the immortalization method of Kampf to progenitor cells isolated from any known transgenic animal model including that taught by Fung-Leung.
Applicant further argues that the references do not suggest modifying the genetic background of progenitor cells used in the method of Kampf, and thus there would have been no motivation to combine the references. This is not persuasive because Kampf specifically teaches that the mast cell progenitors can be isolated from a transgenic animal comprising a transgene useful in studying an inflammatory response. One of ordinary skill would have been motivated to apply the immortalization method of Kampf to progenitor cells isolated from the transgenic animal of Fung-Leung in order to provide a ready source of myeloid cells that are otherwise difficult and time-consuming to isolate. Moreover, one of ordinary skill would have been motivated to prepare immortalized mast cell progenitors via the method of Kamps expressing a human high-affinity IgE receptor alpha subunit as taught by Fung because Fung teaches that IgE binding is species specific and that mouse mast cells expressing the human high-affinity IgE receptor alpha subunit bind to human IgE and allows for the study of human allergic reactions (as suggested by Kampf).
Applicant further argues that one of ordinary skill would not have had a reasonable expectation of success in combining the references because progenitor cell differentiation and receptor expression are complex and dependent on cell lineage. This is not persuasive because Kampf specifically teaches that the mast cell progenitors can be isolated from a transgenic animal comprising a transgene useful in studying an inflammatory response. Moreover, there is no evidence or evident rationale indicating that the progenitor cells of Fung-Leung expressing the human version of the high-affinity IgE receptor alpha subunit would have different differentiation characteristics than other progenitor cells. The cells of Fung-Leung express the human IgE alpha subunit (providing human-specific IgE binding characteristics), which forms a functional receptor with the mouse β and γ chains (Fung-Leung, p. 52, 2nd full ¶). Thus, one of ordinary skill would not expect the cells of Fung-Leung to have substantially different properties than native IgE receptors, other than IgE-specificity. In view of the above, one of ordinary skill in the art would have had a reasonable expectation of success in combining the reference teachings.
Claim Rejections - 35 USC § 112(a) (new matter)
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.
Claims 6 and 16 are rejected under 35 U.S.C. 112(a) 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.
Claim 6 was amended in the Response of 2 Dec. 2025 to recite “wherein said progenitor is capable of terminally differentiating into a non-human mast cell after being cultured for at least 5 days.” The specification as filed does not describe “terminally differentiated” immortalized progenitor cells, and as such amended claim 6 comprises new matter.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1-6, 15 and 16 are rejected under 35 U.S.C. 103 as being unpatentable over the combination of US20090068157 to Kamps et al. in view of Fung-Leung et al., The Journal of experimental medicine 183.1 (1996): 49-56 (cited in IDS of 3 Jan. 2024).
Regarding claims 1 and 2, Kamps teaches a method of producing non-human conditionally immortalized mast cell progenitors, comprising introducing a recombinant nucleic acid molecule comprising an inducible HoxB8 homeobox gene into myeloid bone marrow progenitor cells derived from a non-human animal; and selecting for cells which contain the recombinant nucleic acid molecule ([0009]-[0021]; [0046]; [0048]; [0063]-[0084]; Example 1; claims 1-76). The immortalized progenitor cells can be differentiated into mast cells ([0019]-[0020]; [0048]; [0079]-[0080]; [0116]; claims 16, 45). The myeloid progenitor cells can be isolated from a transgenic animal, e.g. a transgenic mouse comprising a transgene useful in studying an inflammatory response ([0022]; [0058]; [0067]-[0069]; claims 29, 53, 55). Kamps teaches that mature myeloid cells are typically time-consuming to isolate and require large numbers of animals, and that the method provides a ready source of such cells that overcomes such difficulties ([0008]; [0053]; [0084]).
Regarding claim 3, Kamps teaches that the recombinant nucleic acid further comprises an antibiotic resistance gene and the selection comprises culturing in a medium comprising G418 (the antibiotic Geneticin) ([0033]; [0105]; [0108]). Kamps further teaches that HoxB8 expression is inducible by an estrogen receptor-binding inducer, and that the cells are cultured in the presence of an inducer (e.g., tamoxifen, the parent compound of 4-OHT) and IL-3 ([0010]; [0017]; [0074]; Example 1; claims 1, 22).
Regarding claim 4, Kamps teaches deriving the myeloid progenitors by providing whole bone marrow from an animal (e.g., mouse); enriching the bone marrow for hematopoietic progenitors (e.g., by centrifugation); and culturing the cells in the presence of IL-3 ([0018]; Example 1, including [0104]-[0105]; claims 22, 24).
Regarding claims 5-6, Kamps teaches culturing the immortalized progenitors (comprising a recombinant nucleic acid comprising HoxB8 under the control of an inducer) in the presence of an inducer (estradiol) and IL-3 and then withdrawing the inducer and culturing for 6 days so as to obtain non-human mast cells ([0034]; [0116]).
Regarding the recitation in claim 6 that “wherein said progenitor is capable of terminally differentiating into a non-human mast cell after being cultured for at least 5 days”, Kamps teaches that the progenitors were lineage committed to mast cells after culture for 6 days in the absence of the inducer ([0034]; [0116]), and such lineage committed cells can be considered “terminally differentiated”. Moreover, claim 6 requires only that the progenitor is “capable of” such terminal differentiation. Kamps teaches substantially identical cells to those claimed and described in the instant specification (mouse bone marrow hematopoietic progenitors immortalized with a viral vector encoding HoxB8 with an inducible estrogen receptor-binding domain) and such cells would inherently be capable of terminal mast cell differentiation to the same extent as the claimed cells.
Claims 1-6, 15 and 16 differ from Kamps in that: the cells are engineered to express a heterologous high-affinity IgE receptor alpha subunit (claim 1); and the high-affinity IgE receptor alpha subunit is human (claims 15 and 16).
Fung-Leung teaches mast cells isolated from a transgenic mouse expressing a transgene which is a human high-affinity IgE receptor alpha subunit (p. 51-53, under Results). Fung-Leung teaches that mast cells express high affinity IgE receptors which bind to allergen-specific IgE antibodies and induce an inflammatory response, and that human IgE is highly species specific and does not bind to rodent IgE receptors (p. 49, 1st ¶; p. 50, 1st full ¶). Fung-Leung teaches that the transgenic mouse expressing the human high-affinity IgE receptor alpha subunit and mast cells produced therefrom provide an animal model capable of responding to human IgE in allergic reactions and studying such reactions (p. 50, 1st full ¶; p. 54, last ¶).
It would have been obvious to one of ordinary skill in the art at the time the invention was made to use the method of Kamps to produce immortalized mast cell progenitors (and/or mast cells differentiated therefrom) from a transgenic mouse wherein the transgenic mouse expresses a human high-affinity IgE receptor alpha subunit as taught by Fung because it would have been obvious to combine prior art elements according to known methods to yield predictable results. One of ordinary skill would have been motivated to prepare immortalized mast cell progenitors via the method of Kamps expressing a human high-affinity IgE receptor alpha subunit as taught by Fung because Fung teaches that IgE binding is species specific and that mouse mast cells expressing the human high-affinity IgE receptor alpha subunit bind to human IgE and allows for the study of human allergic reactions. Moreover, Kamps teaches that the immortalized progenitor cells provide a ready source of myeloid cells that are otherwise difficult and time-consuming to isolate. Preparing immortalized mast cell progenitors via the method of Kamps expressing a human high-affinity IgE receptor alpha subunit as taught by Fung would have led to predictable results with a reasonable expectation of success because Kamps teaches that the progenitors can advantageously be isolated from a transgenic animal, such as an animal having a transgene related to inflammation/immunity, and Fung teaches that mast cells isolated from the bone marrow of the transgenic mouse express the human high-affinity IgE receptor alpha subunit on the cell surface and functionally bind human IgE (see Fung, p. 50, under Mast Cell Cultures Derived from Bone Marrows; p. 51-53, under Results).
Conclusion
THIS ACTION IS MADE FINAL. 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ROBERT J YAMASAKI whose telephone number is (571)270-5467. The examiner can normally be reached M-F 930-6 PST.
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/ROBERT J YAMASAKI/Primary Examiner, Art Unit 1657
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