Patent Application 15084206 - Compositions for Liquidation of Tumors

Title: Compositions for Liquidation of Tumors

Application Information

Invention Title: Compositions for Liquidation of Tumors
Application Number: 15084206
Submission Date: 2025-05-14T00:00:00.000Z
Effective Filing Date: 2016-03-29T00:00:00.000Z
Filing Date: 2016-03-29T00:00:00.000Z
National Class: 424
National Sub-Class: 093700
Examiner Employee Number: 81547
Art Unit: 1644
Tech Center: 1600

Rejection Summary

102 Rejections: 0
103 Rejections: 3

Cited Patents

The following patents were cited in the rejection:

US 0149000🔗

Office Action Text

DETAILED ACTION

The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .

Applicant's amendment and remarks, filed 3/3/25, are acknowledged.
Claims 1 and 8 have been amended.
Claims 1, 8, 10-11 are pending and are under examination.

The previous 112b rejections are withdrawn in view of Applicant’s claim amendments.

The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
Claims 1, 8, 10-11, are rejected under pre-AIA 35 U.S.C. 103(a) as obvious over US 20060240033, in view of Kornbluth et al., 2006, US 2005/0149000, and 20040228848 (of record).
The ‘033 publication teaches a therapeutic adjuvant composition consisting of an allogeneic MHC class I molecule (i.e. an alloantigen that is expressed on activated TH1 cells and an alloantigen that can be engulfed by APCs, see page 4 and 14). The ‘033 publication teaches that the composition can be combined with other adjuvants and immune stimulatory molecules, such as pro-inflammatory cytokines IFN-gamma or GM-CSF (see page 14, in particular). The ‘033 publication teaches administration by formulation with a polymeric materials or by implantation as a depot to provide long acting formulations (see paragraph 134, in particular). The ‘033 publication teaches that the allogenic MHC acts as an adjuvant for inducing an inflammatory reaction and can be used to augment an immune response to a tumor antigen and can treat tumors (i.e. it would induce IL-12 and tumor liquidation, see page 4, 12). The ‘033 publication teaches that the adjuvant composition can combined with other adjuvants and carriers, and can be administered as a separate formulation without an antigen (see paragraphs 101 and 130, in particular). The ‘033 publication teaches that the composition augments immune responses and provides immunostimulatory activity (see paragraph 115 and 117, in particular). Thus, the ‘033 publication suggest adjuvant composition consisting of an MHC molecule, without another antigen, and with other adjuvants, such as GM-CSF or IFN-gamma, including as an implantable depot composition.
The ‘033 publication does not explicitly teach CD40L or a chip.
Kornbluth et al. teach that CD40L is as adjuvant that induces an immune response and that combinations of adjuvants may provide enhanced or synergistic effects in inducing immunity. In particular, Kornbluth teaches combined use of GM-CSF and IFN-gamma with CD40L as a synergistic combination (see page 1094, in particular). See also the ‘848 publication which teaches that CD40L and cytokines and alloantigen (expressed on allogeneic T cells) are a useful combination for inducing a host anti-tumor immune response.
The ‘000 publication teaches miniaturized drug delivery devices for controlled release of a drug such as immunomodulators (see page 1 and 3, in particular). The ‘000 publication teaches that the delivered drug can be in any pharmaceutically acceptable carrier. The ‘000 teaches that the device is a microchip that can contain the drug molecules within a reservoir section, i.e. the molecules are “embedded” in the chip, see page 1, in particular. The ‘000 publication teaches small devices that can be implanted using a catheter or other injectable means.
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to include CD40L as an adjuvant, as taught by Kornbluth, in the MHC composition of the ‘033 publication. The ordinary artisan at the time the invention was made would have been motivated do so since Kornbluth et al. teach that CD40L is as adjuvant that induces an immune response and that combinations of adjuvants may provide enhanced or synergistic effects in inducing immunity. In particular, Kornbluth teaches combined use of GM-CSF and IFN-gamma combined with CD40L as a synergistic combination. Additionally, the ordinary artisan would have a reasonable expectation of success in combining CD40L, with the cytokines and alloantigen MHC components of the ‘033 publication, since the ‘848 publication teaches that said components (expressed on allogeneic T cells) are a useful combination for inducing a host anti-tumor immune response. Furthermore, the ordinary artisan would be motivated to use the microchip delivery of the ‘000 publication to deliver the adjuvant composition made obvious above, since the ‘000 publication teaches that it allows controlled release of a drug such as an immunomodulator.
Alternatively, it would also be obvious to formulate the adjuvant composition made obvious above in the form of a depot with a polymer for injection as taught by the ‘333 publication. This would amount to a polymer matrix “embedded” with the components and could also meet the limitation of an injectable “wafer” within the scope of the present claims.
Applicant’s arguments filed 3/3/25 have been fully considered, but they are not persuasive.
Applicant argues that the references do not teach or suggest a therapeutic composition comprising at least one exogenous Type 1 inflammatory cytokine.
As noted below in the new 112b rejection, the meaning of the term “exogenous” is unclear. The cited references make obvious compositions comprising isolated cytokines which are considered to be “exogenous” with respect to organism or cell they originate from. The present claims do not explicitly exclude the presence of the cytokines in the chips or wafers. The cited references therefore make obvious a composition within the scope of the instant claims.

Claims 1, 8, and 10-11, are rejected under pre-AIA 35 U.S.C. 103(a) as obvious over 20080112975, in view of WO 2006095330 (of record).
The ‘975 teaches an adjuvant compositions of allogeneic CD4 T cells. The ‘975 publication teaches that the adjuvant activity of the cells relies on their expression of alloantigen, their production of inflammatory cytokines such as IFN-gamma, and their expression of CD40L which causes CD40 ligation and activation of dendritic cells to induce high levels of cytokines (See paragraph 39, in particular). The ‘975 publication teaches that the adjuvant compositions can be administered to a tumor lesion to cause maturation of dendritic cells to stimulate immunity against antigens taken up in the lesion (see paragraphs 9, 12, 19, and 49, in particular). The ‘975 publication explains that the purpose of the adjuvant step of administering the compositions intralesionally is that it causes maturation of dendritic cells to stimulate immunity against endogenous antigens taken up in the lesion (see paragraph 49, in particular).
The ‘033 publication does not explicitly teach the cells embedded in chips or wafers.
WO 2006095330 teaches cellular compositions for local delivery, wherein the cells are present within a biocompatible matrix, such as a collagen scaffold or synthetic polymer foam, tissue engineering scaffold, or the like (see pages 23-24, in particular). WO 2006095330 teaches that the matrix can be fabricated with solid freeform fabrication technology and allows stable aggregation of a cell mixture for delivery to subject (See pages 23-24, in particular). WO 2006095330 teaches that the compositions allow for antigen uptake by APCs (see page 24, in particular).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made provide the allogeneic T cells of the ‘033 publication, embedded in a matrix or scaffold, as taught by WO 2006095330 (i.e. embedded with said CD40L an alloantigen present on said T cells). The ordinary artisan at the time the invention was made would have been motivated do so to allow for local delivery of the cellular compositions in a stable aggregation that allows APC uptake, as taught by WO 2006095330. Since WO 2006095330 teaches that the matrixes can be fabricated as a solid freeform, it would be obvious that this could be in the shape of a “chip” or “wafer”.
The ‘033 publication also teaches that the T cells are formulated for administration with anti-CD3/CD28 beads cross liking their surface such that they are actively secreting Th1 inflammatory cytokines (see paragraph 56, in particular). Therefore, it would be obvious to the ordinary artisan that formulating the cells within a matrix composition would result in active secretion of the cytokines into the matrix (i.e. a therapeutic composition comprising “exogenous” cytokines). Alternatively, the ‘033 publication also teaches that the cells are to be administered to a cryoablated lesion, wherein the cryoablation causes release of inflammatory cytokines such as IFN-gamma (see paragraph 45 and 49, in particular), and it would also be obvious to administer or implant the wafer matrix made obvious above in the presence of TH1 inflammatory cytokines from the lesion, i.e. “exogenous” cytokines.
Regarding the limitation of a “recombinant” cytokine, it is noted that the structure of a cytokine is identical irrespective of its method of production.
Applicant argues that the references to not teach at least one exogenous Type I inflammatory cytokine.
This limitation is met for the reasons set forth above.

Claims 1, 8, 10--11, are rejected under pre-AIA 35 U.S.C. 103(a) as obvious over US 20060240033, in view of Kornbluth et al., 2006, US 2005/0149000, and 20080112975 (of record).
The ‘033 publication teaches an adjuvant composition consisting of an allogeneic MHC class I molecule (i.e. an alloantigen that is expressed on activated TH1 cells and an alloantigen that can be engulfed by APCs, see page 4 and 14). The ‘033 publication teaches that the composition can be combined with other adjuvants and immune stimulatory molecules, such as pro-inflammatory cytokines IFN-gamma or GM-CSF (see page 14, in particular). The ‘033 publication teaches administration by formulation with a solution or with polymeric materials or by implantation by injection as a depot to provide long acting formulations (see paragraph 134, in particular). The ‘033 publication teaches that the allogenic MHC acts as an adjuvant for inducing an inflammatory reaction and can be used to augment an immune response to a tumor antigen and can treat tumors (i.e. it would induce IL-12 and tumor liquidation, see page 4, 12). The ‘033 publication teaches that the adjuvant composition can combined with other adjuvants and carriers, and can be administered as a separate formulation without an antigen (see paragraphs 101 and 130, in particular). The ‘033 publication teaches that the composition augments immune responses and provides immunostimulatory activity (see paragraph 115 and 117, in particular). The ‘033 publication teaches that the composition serves as an adjuvant that can cause local inflammation which increases antigen presentation capability of cells in the vicinity of adjuvant stimulation and triggers a local inflammatory reaction (see abstract, in particular).
The ‘033 publication does not explicitly teach CD40L or a chip.
The ‘975 teaches an adjuvant composition comprising allogeneic cells. The ‘975 publication teaches that the adjuvant activity of the cells relies on their expression of alloantigen, their production of inflammatory cytokines such as IFN-gamma, and their expression of CD40L which causes CD40 ligation and activation of dendritic cells to induce high levels of cytokines (See paragraph 39, in particular). The ‘975 publication teaches that the adjuvant compositions can be used in two different ways, one being as a mixture with an antigen as a vaccine composition, and the second as an adjuvant to endogenous tumor antigens, by administration of the adjuvant composition to the tumor lesion (see paragraphs 9, 12, and 19, in particular). The ‘975 publication explains that the purpose of administering the adjuvant to the tumor lesion is to cause maturation of dendritic cells to stimulate immunity against endogenous antigens taken up in the lesion (see paragraph 49, in particular).
Kornbluth et al. teach that CD40L is as adjuvant that induces an immune response and that combinations of adjuvants may provide enhanced or synergistic effects in inducing immunity. In particular, Kornbluth teaches combined use of cytokines such as GM-CSF and IFN-gamma with CD40L as a synergistic combination (see page 1094, in particular).
The ‘000 publication teaches miniaturized drug delivery devices for controlled release of a drug such as immunomodulators (see page 1 and 3, in particular). The ‘000 publication teaches that the delivered drug can be in any pharmaceutically acceptable carrier. The ‘000 teaches that the device is a microchip that can contain the drug molecules within a reservoir section, i.e. the molecules are “embedded” in the chip, see page 1, in particular. The ‘000 publication teaches small devices that can be implanted using a catheter or other injectable means.
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to include CD40L as an adjuvant, as taught by Kornbluth, in the MHC composition of the ‘033 publication. The ordinary artisan at the time the invention was made would have been motivated do so since Kornbluth et al. teach that CD40L is as adjuvant that induces an immune response and that combinations of adjuvants may provide enhanced or synergistic effects in inducing immunity. In particular, Kornbluth teaches combined use of GM-CSF and IFN-gamma with CD40L as a synergistic combination. Additionally, the ordinary artisan would have a reasonable expectation of success in combining CD40L, with the cytokines and alloantigen MHC components of the ‘033 publication, since the ‘975 publication teaches that said components (expressed on allogeneic T cells) are a useful adjuvant combination for inducing and anti-tumor immune response. The ordinary artisan would have a reasonable expectation of success, since the ‘033 publication specifically teaches that the adjuvant compositions serves to cause local inflammation which increases antigen presentation capability of cells in the vicinity of adjuvant, and the ‘975 publication teaches that a similar alloantigen adjuvant composition that functions in the same way to induce local inflammation can be used in a tumor lesion to induce an immune response to endogenous tumor antigens. Furthermore, the ordinary artisan would be motivated to use the microchip delivery device of the ‘000 publication to deliver the adjuvant composition made obvious above, since the ‘000 publication teaches that it allows for controlled release of a drug such as a immunomodulator.
Alternatively, it would also be obvious to substitute the adjuvant alloantigen cellular compositions of the ‘975 publication that are used for delivery to a tumor lesion, with the alloantigen adjuvant compositions components made obvious by the ‘033 publication and Kornbluth (i.e. MHC, IFN-gamma/GM-CSF and CD40L). Doing so would involve simple substitution of one known element for another to obtain predictable results, since both compositions are taught to serve as adjuvants for causing local inflammation and increasing antigen presentation to stimulate ant anti-tumor immune response. Delivery of the composition to the tumor lesion in the method of the ‘975 publication, via a microchip for sustained release or as a polymer matrix would be obvious for the same reasons set forth above.
Applicant argues that the references do not teach at least one exogenous Type 1 inflammatory cytokine.
This limitation is met for the same reasons set forth above.

The following is a new ground of rejection necessitated by Applicant’s claim amendments.

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, 8, 10-11 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.
The recitation of at least one “exogenous” Type I inflammatory cytokine renders the claims indefinite. Specifically, it is not clear what “exogenous” refers to. For example, does it encompass cytokines that are “exogenous” to their natural source in an organism, i.e. purified or isolated? Is the claim limitation intending to require that the cytokines are not embedded in the chips or wafers? The scope of the intended therapeutic compositions cannot be established. The specification does not define the term “exogenous”. In paragraph 43, the specification discloses chips or wafers that are embedded with a foreign antigen, a molecule which causes maturation of DC and inflammatory cytokines. The speciation teaches that “for example, a wafer embedded with alloantigen and CD40L implanted with either embedded or exogenous cytokines, would fall within the scope of the invention”. The specification does not clarify the metes and bounds of the claimed composition, however. In the example, a chip or wafer is implanted with exogenous cytokines, which describes a method of using the chips or wafers, and not necessarily what is intended to be encompassed by the claimed therapeutic composition, i.e. what actual structures or compositions of matter are contemplated. For example, implanting the chip and further administering “exogenous” cytokines, or implanting a chip into a location rich in “exogenous” cytokines could be performed as a method of implanting a chip. However it is not clear what is envisioned in terms of a composition of matter, i.e. a therapeutic composition. Is the chip required to be in a cytokine solution? Would a chip implanted in a cytokine rich environment meet the limitation? Alternatively, would the claims encompass isolated cytokines embedded in the chip, since isolated cytokines are “exogenous” with respect to their natural source in an organism.

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 extension fee 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 date of this final action.

Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMY E JUEDES whose telephone number is (571)272-4471. The examiner can normally be reached on M-F from 7am to 3pm.
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Amy E. Juedes
Patent Examiner
Technology Center 1600
/AMY E JUEDES/Primary Examiner, Art Unit 1644