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, 4 and 7-9 are currently pending and subject to examination.
Claim Rejections – Withdrawn – Overcome by Amendment
The rejection of claims 4-6 and 10-12 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite is withdrawn.
The rejection of claims 10-12 under 35 U.S.C. 101 is withdrawn.
The rejection of claim 2 under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form is withdrawn.
The rejection of claims 1-3, 7, and 9 under 35 U.S.C. 102(a)(1) as being anticipated by Wu et al. (Cancer Immunol Immunother, Vol. 60, p. 1085–1096, published April 28, 2011) is withdrawn.
The rejection of claims 1-4, 7, and 9 under 35 U.S.C. 102(a)(1) as being anticipated by Wu et al. (Cancer Immunol Immunother, Vol. 60, p. 1085–1096, published April 28, 2011) citing to Hobel & Aigner (WIREs Nanomedicine and Nanobiotechnology, Volume 5, Issue 5, Sep 2013, p. 411-514) is withdrawn.
The rejection of claim(s) 1-4, 7 and 9 under 35 U.S.C. 102(a)(1) as being anticipated by Chen et al. (Biomaterials, Volume 31, Issue 32, November 2010, Pages 8172-8180) is withdrawn.
The rejection of claim(s) 1-7 under 35 U.S.C. 102(a)(1) as being anticipated by Shen et al. (ACS Applied Polymer Materials, Vol 2/Issue 4, p. 1438-1447, Published Feb. 25, 2020) is withdrawn.
The rejection of claims 1-4 and 7-9 under 35 U.S.C. 103 as being unpatentable over Wu et al. (Cancer Immunol Immunother, Vol. 60, p. 1085–1096, published April 28, 2011) citing to Hobel & Aigner (WIREs Nanomedicine and Nanobiotechnology, Volume 5, Issue 5, Sep 2013, p. 411-514), as applied to claims 1-4, 7 and 9 above, and further in view of Huijskens et al. (Cytotherapy, Vol. 17, 2015, p. 613-620) and Chen et al. (Biomaterials, Volume 31, Issue 32, November 2010, Pages 8172-8180) is withdrawn.
The above rejections were overcome by Applicant’s amendments to the claims.
Claim Objections – Necessitated by Amendment
Claims 1, 4, and 7-9 objected to because of the following informalities: the claims recite “brunched” PEI instead of branched PEI. Appropriate correction is required.
Claim Rejections - 35 USC § 102 - New Grounds of Rejection Necessitated by Amendment
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.”
Claim(s) 1, 4, and 7 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hall et al. (Biochimica et Biophysica Acta (BBA) – Bioenergetics, Volume 1847, Issue 3, March 2015, Pages 328-342).
Claim 1 recites:
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This claim reads on a composition comprising branched PEI at a concentration of 3-8 µg/mL. The intended use recited in the preamble is not limiting (MPEP § 2111.02.II).
Hall teaches a composition comprising 10 kDa or 25 kDa branched PEI (PEI-B) as an active ingredient that impacts cellular respiration at concentrations of 4 µg/mL and 8 µg/mL:
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Hall, p. 332, Table 1;
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Hall, p. 329, Fig. 1.
Therefore, claim 1 is anticipated.
Claim 4 limits the molecular weight of the PEI to 10,000 Da to 30,000 Da. As shown in the rejection of claim 1, Hall teaches PEI at a molecular weight of 10 kDa (10,000 Da) and 25 kDa (25,000 Da). Therefore, claim 4 is anticipated.
Claim 7 recites:
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This claim reads on a composition comprising branched PEI at a concentration of 3-8 µg/mL. The intended use recited in the preamble is not limiting (MPEP § 2111.02.II).
As shown in the rejection of claim 1, Hall teaches a composition comprising branched PEI as an active ingredient at concentrations of 4 µg/mL and 8 µg/mL.
Therefore, claim 7 is anticipated.
Claim Rejections - 35 USC § 103 – New Grounds of Rejection Necessitated by Amendment
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
“A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.”
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1, 4, 7 and 9 is/are rejected under 35 U.S.C. 103 as being unpatentable over Shen et al. (ACS Appl. Polym. Mater. 2020, 2, 1438−1447 (of record)).
Claim 1 recites:
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This claim reads on a composition comprising branched PEI at a concentration of 3-8 µg/mL. The intended use recited in the preamble is not limiting (MPEP § 2111.02.II).
Shen teaches a composition comprising 1-10 µg/mL branched PEI to stimulate immune cells:
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Shen, Fig. 2, p. 1440.
1-10 µg/mL encompasses the claimed range and as such a prima facie case of obviousness exists (MPEP § 2144.05).
Therefore, claim 1 was prima facie obvious at the time of filing.
Claim 4 is directed towards the composition of claim 1, wherein the branched PEI has a molecular weight of 10,000 Da to 30,000 Da. As shown in the rejection of claim 1, Shen teaches branched PEI with a molecular weight of 25 kDa (25,000 Da). Therefore, claim 4 was prima facie obvious at the time of filing.
Claim 7 also reads on a composition comprising branched PEI at a concentration of 3-8 µg/mL. The intended use recited in the preamble is not limiting (MPEP § 2111.02.II). Therefore, claim 7 was prima facie obvious for the reasons given in the rejection of claim 1.
Claim 9 is directed towards a method of treating or preventing cancer, the method comprising administering the composition of claim 1 to a subject.
One of ordinary skill in the art would have a reasonable expectation of success to treat cancer with the composition of claim 1 because Shen teaches that PEI stimulates the immune system to treat cancer and specifically suggests a concentration of 8 μg/mL. For example:
Severe infections and advanced cancers remain two significant life-threatening diseases worldwide. Activation of immunity by vaccines stands out as one of the most powerful and indispensable tools to fight against these diseases. (1,2) Adjuvants can efficiently magnify the immune response of vaccines and may serve as intrinsic stimulants (e.g., lipopolysaccharide, LPS) or antigen vehicles (e.g., aluminum and emulsion MF59)…
Polyethylenimine (PEI) is a typical cationic polymer with strong positive charges due to the amino groups, which is known to contribute to a series of specific biological behaviors. In general, PEI quickly binds to negatively charged nucleic acids or peptides and forms small complexes. These particles can easily pass through the plasma membrane and cause lysosomal rupture due to the proton influx and osmotic changes. (14) This process facilitates the delivery of small molecules to antigen-presenting cells (APCs) and T helper 1 (Th1) type-specific anticancer immune response by cross-presentation of antigens, (15) suggesting the extraordinary antigen delivery ability of PEI. Moreover, PEI has been successfully applied in various vaccines against several diseases (e.g., respiratory infections, (16,17) human immunodeficiency virus (HIV) infection, (18−21) renal cell carcinoma, (22) melanoma, (23,24) and others). DermaVir (mannosylated-PEI/plasmid Simian HIV DNA), an in vivo dendritic cell (DC)-based vaccine, is applied to activate HIV-specific Th1 type immune response by topical administration in clinical trials. (19)…
Immunization by PEI alone was found to upregulate a series of immune-related genes in mice, suggesting its potential intrinsic adjuvanticity. (25) Yet, whether PEI has an intrinsic immune-activating property is controversial due to the differences in MW and stimulation concentration used in past studies. (13,17,26) For example, 25 kDa PEI at both 8 and 50 μg/mL showed immunogenicity to dendritic cells or macrophages, respectively, as early as 6 h after treatment in vitro, (13,26)
Shen, p. 1438-1439.
Therefore, claim 9 was prima facie obvious at the time of filing.
Claim(s) 1, 4, and 7-9 is/are rejected under 35 U.S.C. 103 as being unpatentable over Shen et al. (ACS Appl. Polym. Mater. 2020, 2, 1438−1447 (of record)), as applied to claims 1 , 4, 7 and 9 above, and further in view of Hotz et al. (OncoImmunology, Vol. 5, Issue 11, Nov. 4, 2016, e1232219, 11 pages).
The rejection of claims 1, 4, 7 and 9 as obvious over Shen is incorporated herein by reference.
Claim 8 recites:
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.
Shen specifically cultures bone marrow derived dendritic cells (BMDCs), immune cells, with branched PEI in amounts of 1-10 μg/mL to stimulate the BMDCs and promote the production of immune stimulating cytokines such as IL-12:
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Shen, Fig. 2, p. 1440.
While Shen does not teach that this promotes the activity of natural killer cell (NK cells), one of ordinary skill in the art would have a reasonable expectation of success to use this method to promote the activity of NK cells because it is known that co-culture of activated BMDCs which secrete e.g. IL-12 with NK cells promotes the activity of NK cells. For example, Hotz teaches that stimulated BMDC co-cultured with purified NK cells induced high secretion of IFNγ from NK cells:
Breaking tolerance toward tumor tissue by promoting cytotoxic T-cell and natural killer (NK) cell responses is the main goal of cancer immunotherapy.1 Stimulation of pattern-recognition receptors (PRR) induces maturation and activation of dendritic cells (DC), leading to secretion of pro-inflammatory cytokines such as IL-12 and type-I interferons, which are important for the effector functions of T and NK cells.2,3
Hotz, p. 1, col. 1;
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Hotz, p. 5.
Therefore, claim 8 was prima facie obvious at the time of filing.
Given the above teachings, the invention as a whole was prima facie obvious at the time of filing.
Conclusion
No claim is found to be allowable.
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 HEATHER DAHLIN whose telephone number is (571)270-0436. The examiner can normally be reached 9-5.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Lundgren can be reached on (571) 272-5541. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/HEATHER DAHLIN/Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629