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 .
Claim Status
Claims 1, 2-7, 10, 13, 14, 16, 17, 19, 20, 22, 26, 27, 31, and 33 are amended.
Claims 1, 30, 31, 33 are withdrawn.
Claims 38-44 are new.
2-7, 10, 13, 14, 16, 17, 19, 20, 22, 26, 27, and 38-44 are under examination.
Withdrawn Objections
The objection raised against claim 27 is withdrawn in light of claim amendment.
Withdrawn Rejections
Rejections under - 35 USC § 112
The rejection of claims 2,4-7,10,13-14,17,20,22, and 27 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), 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or a joint inventor (or for applications subject to preAIA 35 U.S.C. 112, the applicant), regards as the invention is withdrawn in light of claim
amendment.
Edited Rejections Necessitated by Claim Amendment
Claim Rejections - 35 USC § 112
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 2 and 43 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 term “significant” in claims 2 and 27 is a relative term which renders the claim indefinite. The term “significant” 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. For examination purpose, the term “without significant ex vivo expansion” is interpreted to include 24 hours or less.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 2,3-7,13-14,16-17,19-20,22, 26-27, and 42-44 are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Humeau et al (WO 2002 /18609 A2), as evidenced by ThermoFisher product sheet.
Regarding claims 2 and 43, Humeau et al disclose a method and a composition for the efficient transduction of cells with viral vectors. The method of Humeau et al involves exposing the cells to at least one molecule that binds the cell surface. It should be noted that the molecule that binds the cell surface reads on the “stimulator” recited in the incubation step of instant claim. According to Humeau et al, the contacting step, which involves incubating the cells with the stimulators, may occur prior to, during, or after the cells are exposed to the viral vector or viral particle. (See abstract). In one of the embodiments, Humeau et al teach that the most preferred incubation time for the contacting step is 24 hours, this reads on first incubation time of instant claim since it overlaps with the numerical range recited in instant step (i.e. no more than 48 hours). (See page 18, lines 25-27). The method of Humeau et al also involves the step of transducing the cells with viral vector particles carrying a recombinant nucleic acid and incubating for 24 hours, this reads on the second incubation time. (See page 17-lines 15-22, and page 25-lines 15-16). Humeau et al also state that “ The present invention also includes the use of the transduced cells in other applications, including production of useful gene products and proteins by expression of a nucleic acid present in the vector or therapy of living subjects afflicted, or at risk of being afflicted with a disease. Preferably, the subject is human”. (See page 4-lines 13-16). This implies that the transduced cells will be harvested (and employed in a composition for use in therapy).
Following the discussion above, Humeau et al teach that the optimal incubation time for the contacting and transduction steps is 24 hours each. It should be noted that the overall incubation time for the two steps totals 48 hours, which is within the numerical range specified by instant claim (i.e. no more than 72 hours). Humeau et al further teach that the transduced cells can be administered to a subject for the treatment of disease condition, this reads on the administration step as well as having an effect in the subject. ( See page 27 lines 6-16, lines 24-32). It should also be noted that, in one of the embodiments, Humeau et al contemplate that the “ the post transduction incubation is for a period of about four hours, or
for about one to about seven to ten days. More preferably from about 16 to about 20 hours”. ( See page 26-lines 32-35). The recitation that the cells can be cultured for a period of about four hours implies that the composition of Humeau et al does not require a significant ex vivo expansion before its being administered to a subject. Hence, Humeau et al still anticipate instant claims.
Regarding claim 3, following the discussion of claim 2 above, according to Humeau et al the total incubation time for the contacting and transduction steps is no more than 48 hours, which is within the numerical range specified in the instant claim (i.e. no more than 60 hours)
Regarding claim 4, in one of the embodiments, Humeau et al teach that the most preferred incubation time for the contacting step is 24 hours, this reads on first incubation time of instant claim since it overlaps with the numerical range recited in the instant claim (i.e. 2- 48 hours). (See page 18, lines 25-27).
Regarding claim 5, Humeau et al further disclose that, in a particularly preferred embodiment, the cells are incubated with the viral vector (i.e. the transduction step) for about 24 hours, which overlaps with the elected numerical range given by the instant claim (i.e. 30 mins-24 hours).
Regarding claims 6 and 14, Humeau et al teach that the cells to be transduced can be isolated from peripheral blood and the input composition could include T lymphocytes ( T cells) that express CD4 and CD8 markers ( i.e. an immune effector cell). (See page 21-lines 21-29).
Regarding claims 7 ,13, and 17, Humeau et al state that “The viral vectors may be derived from any source, but are preferably retroviral vectors”, this reads on claim 7. (See page 23-lines 9-10). Humeau et al also teach utilizing CD3 and CD28 antibodies immobilized on bead which bind T cells, activating them and make them more receptive to vector transduction. (See page 25-lines 7-10).
Regarding claim 16, Humeau et al teach that excess cell surface binding molecules may be first removed from the culture before introduction of the vector to the cells. (See page 25-lines 21-24).Humeau et al do not teach removal of excess stimulators by centrifugation; however one with ordinary skill in the art would reasonably expect centrifugation to be used for this purpose.
Regarding claim 19, Humeau et al utilized CD3 and CD28 antibodies (i.e. the stimulator) immobilized on epoxy dynal beads, which is a form of magnetic beads, as evidenced by ThermoFisher product sheet. (See Humeau et al-Example VIII, page 31-lines 27-28), and (Thermofisher product sheet, page 1).
Regarding claim 20, Humeau et al state that “The efficiency of transduction observed with the method of the invention is from about 75- 100%. Preferably, the efficiency is at least about 7 5 to 90%”, this reads on the recited numerical range of instant claim 20. (See page 19-lines 5-9).
Regarding claim 22, Humeau et al teach that the cells to be transduced can be isolated from peripheral blood and the input composition could include T lymphocytes ( T cells) that are enriched for CD4 and/or CD8 markers. ( See page 21-lines 21-28). It should be noted that the isolated T lymphocyte expressing CD4 or CD8 marker from peripheral blood would include a diverse range of T Cell populations of naive cells, memory cells, or memory stem cells.
Humeau et al do not teach the functional outcome recited in instant claim (i.e. the percentage of naïve/memory/or undifferentiated cells that get transduced by the viral vector). However, such results is an inherent property as it recites functional outcomes. This functional outcome is considered inherent, because it flows from performing the active steps of the method of invention, which are taught by Humeau, and there is nothing in applicants' disclosure that shows that these functional outcomes come from something other than the claimed method steps.
Regarding claim 26, Humeau et al also teach that the cells can be cultured in the presence of the cell surface molecules followed by incubation in the presence of IL-2. (See page 18-lines 20-22).
Regarding claim 27, Humeau et al teach that the transduced cells can be harvested and used in gene therapy to cure diseases. Humeau et al do not explicitly teach the washing step before harvesting. However, the washing step to remove extra stimulators and viral particles has been contemplated multiple times in Humeau’s disclosure, therefore the washing step prior to harvesting is inherent in Humeau’s teachings. (See Example II- page 28-29).
Regarding claim 42 and 44, following the discussion of claim 2 above, Humeau et al contemplate that the transduced cells can be directly introduced into a living organism as part of gene therapy. ( See page 27-lines 6-9). However, Humeau et al do not explicitly teach that the output composition is administered to the subject without the ex vivo expansion. Yet, as previously discussed, the method of Humeau et al anticipates the active steps of the instant method. Therefore, the output composition of Humeau et al can inherently be administered to the subject without the need for the ex vivo expansion. In other words, the expansion step, as taught by Humeau et al, is a choice rather than a requirement.
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.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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.
Claims 10, and 38-41 is rejected under 35 U.S.C. 103 as being unpatentable over Humeau et al (WO 2002 /18609 A2), in view of Beauchesne et al (WO 2018/106732 A1).
Regarding claims 10, and 38-41, the teachings of Humeau et al are set forth above.
According to Humeau et al, cells can be transduced with viral particles carrying a recombinant nucleic acid that encodes a therapeutic or prophylactic product for use in gene therapy to treat or prevent a disease. (See page 27-lines 6-32). However, Humeau et al do not specify transducing cells with TCR or CAR directed toward a disease-associated antigen, such as BCMA.
Beauchesne et al teach how to genetically engineer T cells. Beauchesne et al teach that the cells may be transduced with a viral vector containing a nucleic acid that encodes chimeric antigen receptors (CARs) or other antigen-binding receptors such as transgenic T cell receptors (TCRs). Beauchesne et al further disclose that the encoded recombinant antigen receptor, e.g., CAR, is one that is capable of specifically binding to one or more disease-associated antigen, such as BCMA. (See paragraphs [200], and [202-203]). According to Beauchesne et al, the transduced cells can then be used in connection with adoptive cell therapy.
Therefore, it would have been prima facie obvious to one with ordinary skill in the art at the time the invention was filed to combine the teachings of Humeau and Beauchesne to transduce cells with a viral vector expressing a receptor that recognize a tumor-associated antigen (i.e. CAR-BCMA) and use the generated cells in adoptive therapy, as taught by Beauchesne. One would have been motivated to use the method of the invention to transduce cells with a viral vector, as taught by Humeau, because it is highly efficient and generate enough transduced cells for therapeutic purpose. The ordinary artisan would also be motivated to transduce the cells with a viral vector encoding CAR-BCMA, as disclosed by Beauchesne, and use the generated cells in adoptive therapy to treat cancers that overexpress BCMA, such as multiple myeloma.
Response to Arguments
Applicant's arguments filed 12/04/2025 have been fully considered but they are not persuasive.
Applicant argue that Humeau fails to teach that output composition does not require a significant ex vivo expansion before the administering to the subject for the expressing the recombinant nucleic acid and the exerting the effect.
Examiner’s Response to Traversal: Applicant’s arguments have been carefully considered but are not found persuasive. To begin, the recitation of “the output composition does not require significant ex vivo expansion prior administration to a subject” is an intended results of a positively recited method step rather than an active method step that is required by the instant method. This is because such recitation “ i.e. does not require significant ex vivo expansion” refer to the function or purpose of the invention rather than a claim limitation that defines the scope of the claim. According to the MPEP, the recitation of intended results is not a limitation, thereby does not have a patentable weight. As previously discussed, the method of Humeau et al anticipates the active steps of the instant method. Therefore, the output composition of Humeau et al inherently does not require significant ex vivo expansion, instead the expansion step is a choice rather than a requirement. Add to that, the term “significant” is a relative term, which render the term indefinite. For example, what is significant versus insignificant expansion. The term 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.
Applicants Also argue that ThermoFisher product sheet is cited as disclosing CD3 and CD28 antibodies immobilized on epoxy dynal beads, however it does not disclose the method of claim 2.
Examiner’s Response to Traversal: Applicant’s arguments have been carefully considered but are not found persuasive. This is because it appears that Applicant are arguing references individually. Applicants are reminded that the test for obviousness is what the combined teachings of the references would have suggested to a PHOSITA. Thus, one cannot show nonobviousness by attacking references individually.
As per the MPEP, “ One cannot show nonobviousness by attacking references
individually where the rejections are based on combinations of references. In re Keller, 642 F.2d413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., Inc., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Where a rejection of a claim is based on two or more references, a reply that is limited to what a subset of the applied references teaches or fails to teach, or that fails to
address the combined teaching of the applied references may be considered to be an argument
that attacks the reference(s) individually.
Conclusion
No claim is 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to FATIMAH KHALAF MATALKAH whose telephone number is (703)756-5652. The examiner can normally be reached Monday-Friday,7:30 am-4:30 pm EST.
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/FATIMAH KHALAF MATALKAH/Examiner, Art Unit 1638
/Tracy Vivlemore/Supervisory Primary Examiner, Art Unit 1638