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
1. Applicant’s amendment and response filed 11/16/22 and Applicant’s response filed 6/18/25 are acknowledged and have been entered.
2. Applicant's election with traverse of Group I and species of NK cells as the cell type produced and the cell mobilizing agent resveratrol, in Applicant’s response filed 6/18/25 is acknowledged.
The basis for Applicant’s said traversal is of record in the response filed 6/18/25 on page 3, briefly that the subject matter of claim 1 (claim 1 is canceled) would be required to be searched regardless of which group of claims is elected, and hence would not present an undue burden.
Regarding undue burden, the M.P.E.P. 803 (July 1998) states that:
“For purposes of the initial requirement, a serious burden on the examiner may
be prima facie shown if the examiner shows by appropriate explanation
either separate classification, separate status in the art, or a different field of search”.
The restriction requirement enunciated in the previous Office Action meets this criterion of serious burden and therefore establishes that serious burden is placed on the Examiner by the examination of additional Groups.itional Groups. The inventions are distinct for reasons elaborated in paragraph 1 of the previous Office Action mailed 4/18/25.
The requirement is still deemed proper and is therefore made FINAL.
Claims 244-256 read on the elected species.
Accordingly, claim 259 (non-elected species of Group I) and claims 257 and 258 (non-elected Group II) are withdrawn from further consideration by the Examiner, 37 CFR 1.142(b), as being drawn to non-elected inventions.
Claims 244-256 read on the elected species and are presently being examined as they read upon the elected species..
3. The lengthy specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
4. Claim interpretation: The open transitional phrase “comprising” opens the claims to include unrecited steps and/or ingredients. The specification discloses at [00200] that the term “about” means an acceptable error for a particular value as determined by one of ordinary skill in the art, which depends in part on how the value is measured or determined. The specification further discloses non-limiting values for about, e.g., within 1-4 standard deviations, or within 0.05% to 50% of a given value or range.
5. 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.
6. Claims 244-256 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The specification does not disclose how to use the instant invention, a method of producing a cell population comprising natural killer (NK) cells, the said method comprising the steps and ingredients recited in instant base claim 244 or claim 246, including the limitations recited in the dependent claims, and wherein in dependent claim 252 the stem cell mobilization factor is the aryl hydrocarbon receptor inhibitor resveratrol, and wherein the hematopoietic stem or progenitor cells can be from any animal.
The specification has not enabled the breadth of the claimed invention because the claims encompass: a method whereby critical steps and/or ingredients for producing a cell population comprising NK cells are missing from the claims. The claims under examination are drawn to a method of producing a cell population comprising NK cells; however:
(1) the instant method claims recite the same initiator media in the same three method steps as does withdrawn method claim 259 that is drawn to a method of producing a cell population comprising both NK cells and ILC3 cells (and although the said withdrawn claim has additional limitations pertaining to exclude ingredients in the alternative to one another, these said excluded ingredients are also not recited in the instant method claims) so it is unpredictable that the basic method steps and/or ingredients can produce the NK cell population;
(2) it is unpredictable that the method steps and/or ingredients recited in the claims alone can accomplish the production of a cell population comprising NK cells- note that at least 80% of the NK cells must be viable claim as recited in claim 244 and its dependent claims), must comprise the recited phenotype (claims 245 and 248), must be generated using an additional factor or factors recited in the alternative in claim 255 or claim 256, and must be generated from any hematopoietic stem or progenitor cell that is recited in claim 249 and that is from any animal species that has them.
The state of the art is such that it is unpredictable in the absence of appropriate evidence whether the claimed method can be used for its recited purpose without the recitation of additional steps and/or ingredients.
In addition, the working examples in the specification are not representative of the breadth of the claims, in terms of the hematopoietic stem or progenitor cells, the combinations of ingredients, cell densities, and culturing times.
The specification discloses at [0009] “Natural killer cells and/or ILC3 cells produced by the three-stage methods provided herein are referred to herein as “NK cells produced by the three-stage method,” “ILC3 cells produced by the three-stage method,” or “NK cells and/or ILC3 cells produced by the three-stage method.”
The specification discloses a working example of a three-stage method of producing NK cells from CD34+ hematopoietic stem or progenitor cells wherein the media are as follows:
[00489] Stage 1 Medium: Stem Cell Growth Medium (SCGM) (CellGroR), 10% human AB serum, supplemented with 4.5 U/ml LMWH, 25 ng/ml rhTPO, 25 ng/ml rhFlt3L, 27 ng/ml rhSCF, 25 ng/ml rhIL-7, 0.05 ng/ml rhIL-6, 0.25 ng/ml rhG-CSF, 0.01 ng/ml rhGM-CSF, 0.1% gentamicin, and 1 to 10 uM SR-1 (i.e., Stemregenin-1 as the mobilizing agent);
[00490] Stage 2 Medium: 90% SCGM, 10% human AB serum, supplemented with 4.5 U/ml LMWH, 25 ng/ml rhFlt3L, 27 ng/ml rhSCF, 25 ng/ml rhIL-7, 20 ng/ml rhIL-15, 0.05 ng/ml rhIL-6, 0.25 ng/ml rhG-CSF, 0.01 ng/ml rhGM-CSF, 0.1% gentamicin, and 1 to 10 uM SR-1;
[00491] Stage 3 Medium: 90% STEMMACTM, 10% human AB serum, 0.25 mM 2-mercaptoethanol, supplemented with 22 ng/ml rh SCF, 1000 U/ml rhIL-2, 20 ng/ml rhIL-7, 20 ng/ml rhIL-15, 0.05 ng/ml rhIL-6, 0.25 ng/ml rhG-CSF, 0.01 ng/ml rhGM-CSF and 0.1% gentamicin.
In this example, Example 1, the CD34+ hematopoietic stem cells are seeded and cultured in various amounts for various numbers of days successively in the different media and harvested on day 36. The specification further discloses that the SR-1 was tested at three different concentrations, 1 uM, 10 uM and 30 uM, whereby the intermediate value of 10uM SF-1 resulted in a higher cytotoxicity than the other two concentrations. Another aryl hydrocarbon receptor inhibitor besides SF-1 was also tested ([00498]). The specification discloses that CD3-CD56+ NK cells were routinely achieved at about 88.3%+/-6.3%) ([00505]). The specification discloses that the cells in this majority exhibit a developmentally intermediate immunophenotype characterized by low or negative expression of CD16 and KIRs, but expressing NCRs (NKp30, p46 and p44), c-lection receptors (CD94, NKG2D and CD161), DNAM-1, 2B4, CD117, CD11a+, cytolytic mediators perforin and granzyme positive, regulator of NK cell maturation and cytolytic function (i.e., EOMES, eomesodermin) positive([00505]), ROR negative, IL1R1 negative, and contained both CD94- and CD94+ cells. However the smaller population of cells in the final preparation were CD11a- cells that were hypothesized to be ILC3 cells having a phenotype of CD94-, ROR positive and IL1R1 positive, and perforin and EOMES negative ([00514]).
In Example 7, IL-7, SCF, IL-2, SR-1 and IL-15 were varied in the third medium with regard to their presence at a same concentration or absence thereof, with the result that “In summary, low SCF in the third medium and the presence of SR1 (a different aryl hydrocarbon receptor inhibitor than Applicant’s elected species resveratrol) in the third medium was found to favor NK (CD11a+) cell production, whereas the absence of SR1 in the third medium was found to favor ILC3 (CD11a-) cell production” ([00531]).
The specification discloses at [0022] that the hematopoietic stem or progenitor cells in certain embodiments are mammalian cells such as human, primate, canine, rodent or other mammal. The specification discloses at [00141] “The hematopoietic cells used to produce the NK cells and/or ILC3 cells, and NK cell populations and/or ILC3 cell populations, may be obtained from any animal species.” The specification differentiates NK cells from ILC3 cells at para [00108] and [00109]. The specification discloses at [00114] “As used herein, the “undefined component “is a term of art in the culture medium filed that refers to components whose constituents are not generally provided or quantified. Examples of an “undefined component” include, without limitation, serum, for example, human serum (e.g., human serum AB) and fetal serum (e.g., fetal bovine serum or fetal calf serum.)” The specification discloses that in certain embodiments, the hematopoietic cells are CD34- ([00149]), while in other embodiments, the hematopoietic cells are CD34+ ([00150]), or can be a mixture of both [00155]). The specification discloses stem cell mobilizing compounds at [00229]-[00329]).
Evidentiary reference Simoni et al (Immunity, 2017, 46: 148-161, IDS reference) teaches that NK cells and ILC3 cells are different innate immune cells in humans that possess different phenotypes and functionalities. Simoni et al teach, for example, that in contrast to NK cells, helper type ILCs such as ILC3 do not possess efficient cytotoxic capacities. Simoni et al teach that there are differences between mice and human innate immune cells (see entire reference, especially graphical abstract, introduction section at the first paragraph, first sentence of the first full para at column 2 on page 158, last paragraph of reference).
There is insufficient guidance in the specification as to how to use the instant invention. Undue experimentation would be required of one skilled in the art to practice the instant invention. See In re Wands 8 USPQ2d 1400 (CAFC 1988).
7. 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.
8. Claims 245, 248, 249 and 256 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.
See claim interpretation section above in this office action.
a) Claim 245 is indefinite in the recitation of “wherein said third population of cells comprise natural killer cells that are 1) CD94+ or CD16+, 2) CD94- or CD16-“ because it is not clear what is meant, i.e., the specification at [00516] discloses that expression of CD16 was restricted to CD94+ cells, while the specification at [00514] discloses that the CD11a+ (NK) cells contain both CD94- and CD94+ cells, while the CD11a- cells (ILC3) were CD94-.
b) Claim 248 is indefinite in the recitation of “wherein said natural killer cells express…2) either RORgt or IL1R1” because it is not clear what is meant, as the specification at [00514] discloses that the CD11a+ NK cells are negative for both RORgt and IL1R1.
c) A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 249 recites the broad recitation ”wherein said hematopoietic stem or progenitor cells are mammalian cells”, and the claim also recites “preferably wherein hematopoietic stem or progenitor cells are human cells” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
d) Claim 256 is indefinite in the recitation of “about” at multiple locations in the claim, because it is not clear what is meant. Although as stated above in the claim interpretation section of this office action, the specification discloses at [00200] that the term “about” means an acceptable error for a particular value as determined by one of ordinary skill in the art, which depends in part on how the value is measured or determined, the term is indefinite. For example, claim 256 recites the limitation “about” before the recitation “days” at parts 3, and 9, and it is therefore not clear what the limitation means. In addition the claim also recites the limitation “about” before the recitation of a number of “cells/ml”, and as there are different methods for measuring cells, the claim is indefinite. (The specification further discloses non-limiting values for about, e.g., within 1-4 standard deviations, or within 0.05% to 50% of a given value or range.)
9. Claim 252 is rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of the alternatives recited in claim 252 is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: in the instant case, the claim recites species that do not share a single structural similarity, as the claims recite different aryl hydrocarbon receptor inhibitors having different structures, as well as recites pyrimido (4, 5-b) indole derivatives having different structures from each other and from the aryl hydrocarbon receptor inhibitors. For example, the aryl hydrocarbon receptor inhibitor that is resveratrol. (at part “2)”) has a different structure from the aryl hydrocarbon receptor inhibitor recited at part “3)”, as is evidenced by Gambini et al (Oxid. Med. Cell. Longevity, 2015, article ID 837042, pages 1-13, IDS reference) (see entire reference, especially Figure 1), and do not share a single structural similarity.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
10. 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.
11. 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.
12. Claims 244-246 and 248-256 are rejected under 35 U.S.C. 102(a)(i) as being anticipated by WO 2014/028453 A2 (IDS reference, pub date 2/20/2014, IDS reference).
WO 2014/028453 A2 teaches a three step method for producing a cell population comprising NK cells comprising the steps of: culturing hematopoietic stem cells or progenitor cells in a first medium to produce expanded and differentiated cells, subsequently culturing the expanded cells in a second medium in which the cells expand further and differentiate into NK cells [0007], and subsequently culturing the cells in a third medium for a specified time period, wherein in certain embodiments the third medium comprises factors that promote differentiation and activation of the NK cells [0024].
WO 2014/028453 A2 teaches that in stage 1 the medium may comprise 10% human AB serum, TPO, SCF, IL-7, Flt3L, resveratrol ( i.e., a stem cell mobilizing agent) and (optionally, but in some embodiments lacking) LWH (LMWH) (e.g , [0024]), while in stage 2, the medium may comprise human serum, SCF, IL-7, Flt3L, and IL-15, resveratrol and may or may not comprise LWH (LMWH) (e.g., [0013], [0025], [0027]-[0029], table 7); said reference additionally teaches that in all stages IL-6, G-CSF, GM-CSF may also be used therein ([00188]-[0198]). WO 2014/028453 A2 teaches that the third medium can comprise one or more cytokines such as SCF, IL-15, IL-7, IL-2, IL-6, G-CSF and/or GM-CSF, wherein in an embodiment, the third medium comprises the cytokines SCF, IL-15, IL-7, IL-2 and G-CSF, IL-6 and GM-CSF (e.g., [0024]). The specification further discloses that the third medium may also comprise human AB serum ([0029]), and may result in an NK cell population that comprises at least about 80% CD3-CD56+ NK cells (e.g., [0052]). WO 2014/028453 A2 teaches that the cytokines or other factors are not within an undefined component of the media (e.g., [0007]).
WO 2014/028453 A2 teaches that the hematopoietic stem cells or progenitor cells may be collected from placental perfusate, umbilical cord blood, placental blood, peripheral blood, spleen, liver and/or bone marrow, and the hematopoietic (stem) cells may be CD34+ cells (e.g., [00141], [00143],[00146] ). WO 2014/028453 A2 teaches maintaining the cells a particular density range ([00187]), culturing periods in days that meet the claim limitations recited in claim 256 (e.g., [0030]-[0035],[00175], [0195]-[0198]), and a seeding density of from 2 x 104 to 5 x 104 cells/ml (e.g., [00385]). WO 2014/028453 A2 teaches that in some embodiments, the first and/or second medium does not comprise added desulphated glycosaminoglycans (e.g., [0024], [0025]) (See entire reference, including claims, and the aforementioned paragraphs).
Although the art reference does not explicitly teach the complete phenotype recited in instant base claim 246 (i.e., it teaches CD56+, CD3-, but not also CD11a+), the art reference does teach the same method steps as recited in the instant claims. In addition, although the art reference does not explicitly teach that the NK cells produced in the method express perforin and eomes (claim 248), the art reference does teach that NK cells express perforin that forms pores in the cell membrane of the target cells (e.g., at [0002]), and the art teaches the same ingredients and same method steps recited in the claims. Therefore the claimed method appears to be the same as the method of the prior art absent a showing of differences. Since the Patent Office does not have the facilities for examining and comparing the method of the instant invention to those of the prior art, the burden is on Applicant to show a distinction between the method of the instant invention and that of the prior art. See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977).
Claim 245 is also included in this rejection because the art reference teaches that a percentage of NK cells at the end of the method that are CD94+ (mature NK cells) and also teaches that in some embodiments the NK cells are CD16- (e.g., [00185] and [00311], respectively).
Claim 249 is also included in this rejection because although the art reference teaches that any hematopoietic stem or progenitor cells may be used in the method and the art reference does not explicitly teach that the cells are mammalian or human, the art reference teaches that stem cells are obtained from human placenta (e.g., at 5.4.2) and incorporates by reference (at [00201]) US 7,045,148 (IDS reference) which discloses isolating hematopoietic stem cells from mammals, including humans (e.g., claims and “other publications” section) and also US 7,468,276 (IDS reference) which discloses human placental stem cells (e.g., claims).
13. 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.
14. Claim 244-256 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2014/028453 A2 (IDS reference, pub date 2/20/2014, IDS reference), as evidenced by Montaldo et al (Cytometry Part A, 2013, 83A: 702-713).
WO 2014/028453 A2 teaches a three step method for producing a cell population comprising NK cells comprising the steps of: culturing hematopoietic stem cells or progenitor cells in a first medium to produce expanded and differentiated cells, subsequently culturing the expanded cells in a second medium in which the cells expand further and differentiate into NK cells [0007], and subsequently culturing the cells in a third medium for a specified time period, wherein in certain embodiments the third medium comprises factors that promote differentiation and activation of the NK cells [0024].
WO 2014/028453 A2 teaches that in stage 1 the medium may comprise 10% human AB serum, TPO, SCF, IL-7, Flt3L, resveratrol ( i.e., a stem cell mobilizing agent) and (optionally, but in some embodiments lacking) LWH (LMWH) (e.g , [0024]), while in stage 2, the medium may comprise human serum, SCF, IL-7, Flt3L, and IL-15, resveratrol and may or may not comprise LWH (LMWH) (e.g., [0013], [0025], [0027]-[0029], table 7); said reference additionally teaches that in all stages IL-6, G-CSF, GM-CSF may also be used therein ([00188]-[0198]). WO 2014/028453 A2 teaches that the third medium can comprise one or more cytokines such as SCF, IL-15, IL-7, IL-2, IL-6, G-CSF and/or GM-CSF, wherein in an embodiment, the third medium comprises the cytokines SCF, IL-15, IL-7, IL-2 and G-CSF, IL-6 and GM-CSF (e.g., [0024]). The specification further discloses that the third medium may also comprise human AB serum ([0029]), and may result in an NK cell population that comprises at least about 80% CD3-CD56+ NK cells (e.g., [0052]). WO 2014/028453 A2 teaches that the cytokines or other factors are not within an undefined component of the media (e.g., [0007]).
WO 2014/028453 A2 teaches that the hematopoietic stem cells or progenitor cells may be collected from placental perfusate, umbilical cord blood, placental blood, peripheral blood, spleen, liver and/or bone marrow, and the hematopoietic (stem) cells may be CD34+ cells (e.g., [00141], [00143],[00146] ). WO 2014/028453 A2 teaches maintaining the cells a particular density range ([00187]), culturing periods in days that meet the claim limitations recited in claim 256 (e.g., [0030]-[0035],[00175], [0195]-[0198]), and a seeding density of from 2 x 104 to 5 x 104 cells/ml (e.g., [00385]). WO 2014/028453 A2 teaches that in some embodiments, the first and/or second medium does not comprise added desulphated glycosaminoglycans (e.g., [0024], [0025]) WO 2014/028453 A2 teaches that CD56+CD3- is the phenotype of NK cells (e.g., [0040]) and that NK cells can be isolated using antibodies to CD56 and CD3, selecting for CD56+CD3- cells (e.g., [00199]-[00200]). (See entire reference, including claims, and the aforementioned paragraphs).
Although WO 2014/028453 A2 teaches that NK cells may be isolated on the basis of their CD56+CD3- phenotype, WO 2014/028453 A2 does not teach wherein the method comprises a further step of isolating CD11a+ cells from the third population of cells to produce a fourth population of cells, wherein the fourth population of cells comprises NK cells that are CD56+CD3- and CD11a+, as is recited in dependent claim 247.
It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to have isolated CD56+CD3- in a further step in the method taught by WO 2014/028453 A2.
One of ordinary skill in the art would have been motivated to do this, and with a reasonable expectation of success in doing so, in order to obtain a more purified population of NK cells.
Note that as evidentiary reference Montaldo et al teaches that NK cells are CD56 positive as well as CD2, CD58 and LGA-1 (CD11a/CD118) positive, isolating the CD56+CD3- cells also isolates the CD11a+ cells (and WO 2014/028453 A2 teaches that NK cells may be isolated on the basis of their CD56+CD3- phenotype as stated above).
Although the art reference does not explicitly teach that the NK cells produced in the method express perforin and eomes (claim 248), the primary art reference does teach that NK cells express perforin that forms pores in the cell membrane of the target cells (e.g., at [0002]), and the art teaches the same ingredients and same method steps recited in the claims. Therefore the claimed method appears to be similar to the method of the prior art absent a showing of unobvious differences. Since the Patent Office does not have the facilities for examining and comparing the method of the instant invention to those of the prior art, the burden is on Applicant to show a distinction between the method of the instant invention and that of the prior art. See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977).
Claim 245 is also included in this rejection because the primary art reference teaches that a percentage of NK cells at the end of the method that are CD94+ (mature NK cells) and also teaches that in some embodiments the NK cells are CD16- (e.g., [00185] and [00311], respectively).
Claim 249 is also included in this rejection because although the primary art reference teaches that any hematopoietic stem or progenitor cells may be used in the method and the art reference does not explicitly teach that the cells are mammalian or human, the art reference teaches that stem cells are obtained from human placenta (e.g., at 5.4.2) and incorporates by reference (at [00201]) US 7,045,148 (IDS reference) which discloses isolating hematopoietic stem cells from mammals, including humans (e.g., claims and “other publications” section) and also US 7,468,276 (IDS reference) which discloses human placental stem cells (e.g., claims).
15. 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.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
16. Court rulings have been quite clear that ONLY DIVISIONAL applications are entitled to the shield from double patenting under 35 USC 121. Indeed, in AMGEN INC v. HOFFMANN LA ROCHE LTD GMBH LA (Nos. 2009-1020, 2009-1096) the court discusses this issue at length and states:
Turning to the legislative history, the court observed that a House Report also referred specifically to “divisional application[s].” Id. Notably absent from the legislative history, in the court's view, was a suggestion “that the safe-harbor provision was, or needed to be, directed at anything but divisional applications.” Id. at 1361. From there, the court “conclude^] that the protection afforded by section 121 to applications (or patents issued therefrom) filed as a result of a restriction requirement is limited to divisional applications.” Id. at 1362. Accordingly, the court decided that the § 121 safe harbor did not apply to the patent before it, which issued from a continuation-in-part application. Id.
We are persuaded by the reasoning in Pfizer that the § 121 safe harbor provision does not protect continuation applications or patents descending from only continuation applications. The statute on its face applies only to divisional applications, and a continuation application, like a continuation-in-part application, is not a divisional application.
Given that Applicant chose to file the 16/099,676 case that issued as US 11,180,731 as a separate unrelated application, not as a DIV of the instant application, the instant rejection has been set forth.
Claims 244-256 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 11,180,731, as evidenced by Montaldo et al (Cytometry Part A, 2013, 83A: 702-713).
Although the claims at issue are not identical, they are not patentably distinct from each other for the following reasons.
Claims 1-18 of US 11,180,731 are drawn to a method of treating an individual having AML or MM (multiple myeloma) or of suppressing the proliferation of MM cells comprising administering an effective amount of a cell population comprising NK cells, wherein the cell population comprising NK cells in produced by a method comprising the steps of culturing HSC or progenitor cells in a first medium comprising a stem cell mobilizing agent and Tpo to produce a first population of cells, culturing the first population of cells in a second medium comprising a stem cell mobilizing agent and IL-15 and lacking Tpo to produce a second population of cells, and culturing the second population of cells in a third medium comprising IL-2 and IL-15 and lacking a stem cell mobilizing agent and LMWH to produce a third population of cells, wherein said stem cel mobilizing agent is an aryl hydrocarbon receptor inhibitor, and wherein the third population of cells comprising NK cells that are CD56+,CD3- or CD16+, and CD94+ or CD94-, and wherein at least 80% of the NK cells are viable. The hematopoietic stem cells are CD34+ hematopoietic stem cells (HSCs). The first or second medium may additionally comprising one or more of LMWH, Flt-3L, SCF, IL-6, IL-7, G-CSF or GM-CSF, that are not comprised within an undefined component of serum or serum. The third medium may additionally comprise one or more of SCF, IL-6, IL-7, G-CSF or GM-CSF. The stem cell mobilizing agent that is an aryl hydrocarbon receptor inhibitor may be resveratrol. The HSCs in the first medium may be cultured for 7-13 days, 8-12 days or for about 10 days, the culturing in the second medium is for 2-6 days, 3-5 days or 4 days. The culturing in the third medium is for 10-20 days, 15-25 days, or 21 days.
Note that as evidentiary reference Montaldo et al teaches that NK cells are CD56 positive as well as CD2, CD58 and LGA-1 (CD11a/CD118) positive, isolating the CD56+CD3- cells also isolates the CD11a+ cells (and WO 2014/028453 A2 teaches that NK cells may be isolated on the basis of their CD56+CD3- phenotype as stated above).
Although the art reference does not explicitly teach that the NK cells produced in the method express perforin and eomes (claim 248), the claims of ‘731 recite the same ingredients and same method steps as are recited in the instant claims. Therefore the claimed method appears to be similar to the method recited in the claims of ‘731 absent a showing of unobvious differences. Since the Patent Office does not have the facilities for examining and comparing the method of the instant invention to that of the claims of ‘731, the burden is on Applicant to show a distinction between the method of the instant invention and that of the claims of ‘731. See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977).
Instant dependent claim 249 is included in this rejection because human HSCs are an obvious variant of HSCs, and human patients are an obvious variant of those having AML or MM who are being treated.
Claims 244-256 are directed to an invention not patentably distinct from claims 1-18 of commonly assigned, as enunciated supra.
The U.S. Patent and Trademark Office may not institute a derivation proceeding in the absence of a timely filed petition. The USPTO normally will not institute a derivation proceeding between applications or a patent and an application having common ownership (see 37 CFR 42.411). Commonly assigned US 11,180,731, discussed above, may form the basis for a rejection of the noted claims under 35 U.S.C. 102 or 103 if the commonly assigned case qualifies as prior art under 35 U.S.C. 102(a)(2) and the patentably indistinct inventions were not commonly owned or deemed to be commonly owned not later than the effective filing date under 35 U.S.C. 100(i) of the claimed invention.
In order for the examiner to resolve this issue the applicant or patent owner can provide a statement under 35 U.S.C. 102(b)(2)(C) and 37 CFR 1.104(c)(4)(i) to the effect that the subject matter and the claimed invention, not later than the effective filing date of the claimed invention, were owned by the same person or subject to an obligation of assignment to the same person. Alternatively, the applicant or patent owner can provide a statement under 35 U.S.C. 102(c) and 37 CFR 1.104(c)(4)(ii) to the effect that the subject matter was developed and the claimed invention was made by or on behalf of one or more parties to a joint research agreement that was in effect on or before the effective filing date of the claimed invention, and the claimed invention was made as a result of activities undertaken within the scope of the joint research agreement; the application must also be amended to disclose the names of the parties to the joint research agreement. A showing that the inventions were commonly owned or deemed to be commonly owned not later than the effective filing date under 35 U.S.C. 100(i) of the claimed invention will preclude a rejection under 35 U.S.C. 102 or 103 based upon the commonly assigned case. Alternatively, applicant may take action to amend or cancel claims such that the applications, or the patent and the application, no longer contain claims directed to patentably indistinct inventions.
18. Claim 256 is objected to because of the following informalities:
Part “9)” of claim 256 recites “culturing said second population of cells in said third medium for about 21 days, and:” followed by items labeled as “1)” through “8)” without being indented under part “9)” or being labeled as ‘a’ through ‘h’, for example.
Appropriate correction is required.
19. No claim is allowed.
20. Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARIANNE DIBRINO whose telephone number is (571)272-0842. The examiner can normally be reached on M, T, Th, F.
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/Marianne DiBrino/
Marianne DiBrino, Ph.D.
Patent Examiner
Group 1640
Technology Center 1600
/MICHAEL SZPERKA/ Primary Examiner, Art Unit 1641