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 .
Status of Claims
Claims 1-5 as originally filed on 10/28/2024 are currently pending and under consideration on the merits.
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 3 and 5 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 term “about” in claims 3 and 5 is a relative term which renders the claim indefinite. The term “about” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree (e.g. a definition of the term), and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Correction is required.
Claim Rejections - 35 USC § 102 and 103
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.
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 1 is rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Crabbé et al. (Cellular Microbiology (2011) 13(3), 469–481; Reference U) as evidenced by Rothblat et al. (In Vitro (1976), 12(8), 554-557; Reference V) and Zheng et al. (Biotechnol. Prog. 2006, 22, 1294-1300; Reference W).
“Cytokines” as set forth in claim 1 is read in light of the specification as being inclusive of growth factors, as Applicant includes
Crabbé teaches a cell culture medium capable of generating human alveolar macrophage-like cells from a human monocyte cell line, comprising GTSF-2 medium (the basal medium) and 10% fetal bovine serum (page 477, the 1st paragraph under “Experimental Procedures”; see page 478, the 1st three paragraphs for the further coculture of human U937 monocytes with A549 alveolar epithelial cells or the further treatment of human U937 monocytes with phorbol 12-myristate 13-acetate (PMA) to generate alveolar macrophages; see ICAM-1 and functional phagocytic activity as markers of alveolar macrophages at the paragraph spanning pages 472-474 and Fig. 4).
Regarding claim 1, Crabbé is silent if the culture medium comprises a surfactant and two or more cytokines. However, the fetal bovine serum of Crabbé inherent comprises both surfactants and growth factors/cytokines as evidenced by Rothblat and Zheng. Rothblat teaches that bovine serum inherent comprises lipids such as phospholipids and free fatty acids (e.g. surfactants) (Table 1). Zheng teaches that fetal bovine serum (FBS) inherently comprise TGF-β1 and other growth factors (Table 3). Therefore, Crabbé as evidenced by Rothblat and Zheng anticipates or reads on claim 1.
Regarding a cell culture medium capable of generating human alveolar macrophage-like (AML) cells from blood-derived monocytes of claim 1, where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." Also, alternate rejections under both 102 and 103 are appropriate when Applicant claims a composition in terms of a function or property and the composition of the prior art is the same as that of the claim but does not explicitly disclose the function or property. See M.P.E.P. § 2112; once a substantially identical product/composition has cited and a rationale tending to show inherency is set forth, the burden shifts to Applicant to overcome the 102 rejection by showing the prior art product lacks the claimed function/property, and to overcome the 103 rejection by further showing that any difference in the claimed function/property is non-obvious.
In this case, the cell culture media composition of Crabbé as evidenced by Rothblat and Zheng is substantially similar to the claimed cell culture media composition because Crabbé teaches a cell culture medium capable of generating human alveolar macrophage-like cells from a human monocyte cell line, the medium comprising GTSF-2 medium (the basal medium) and 10% fetal bovine serum and meeting every structural limitation of the claim as evidenced by Rothblat and Zheng. Therefore, the burden is shifted back to Applicant to show by a preponderance of evidence that Crabbé as evidenced by Rothblat and Zheng does not anticipate claim 1 and claim 1 is otherwise nonobvious.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the invention was filed.
Claims 2 and 3 are rejected under 35 U.S.C. 103 as being unpatentable over Crabbé as evidenced by Rothblat and Zheng as applied to claim 1 above, and further in view of Kerecman et al. (Inflamm. res. 57 (2008) 118–125; Reference X).
The teachings of Crabbé as evidenced by Rothblat and Zheng are relied upon as set forth above.
Regarding claim 2, Crabbé, Rothblat and Zheng do not teach calfactant. Regarding claim 2, Crabbé, Rothblat and Zheng do not teach a calfactant concentration at about 100 μg/ml.
Kerecman teaches that culturing alveolar macrophages in vitro with calfactant and at a concentration range of 25-1,000 μg/ml (page 119, subheadings “Cell Culture” and “Experimental Protocol”) significantly reduces LPS-stimulated cytokine secretion 12 hours and 24 hours after LPS treatment (1st paragraph under the “Results” on page 120 and Table 1), reading on claims 2 and 3.
Regarding claims 2 and 3, it would have been obvious to a person of ordinary skill in the art before the invention was filed to add the 25-1,000 μg/ml calfactant of Kerecman to the culture media composition of Crabbé. A person of ordinary skill in the art would have had a reasonable expectation of success to do so because both Crabbé and Kerecman are directed towards cell culture media compositions for culturing alveolar macrophages in vitro. The skilled artisan would have been motivated to do so because Kerecman teaches that culturing alveolar macrophages in vitro with calfactant and at a concentration range of 25-1,000 μg/ml significantly reduces LPS-stimulated cytokine secretion 12 or 24 hours after LPS treatment, and so the addition would be predictably advantageous to further study cellular mechanisms of inflammation in the alveolar macrophage like cells of Crabbé.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the invention was filed.
Claims 4 and 5 are rejected under 35 U.S.C. 103 as being unpatentable over Crabbé as evidenced by Rothblat and Zheng as applied to claim 1 above, and further in view of Yu et al. (Immunity (2017), 47, 903–912; provided in the IDS dated 10/28/2024) and Thomassen et al. (CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY (1996), 80(3), 321-324; Reference U2).
The teachings of Crabbé as evidenced by Rothblat and Zheng are relied upon as set forth above.
Regarding claim 4, Crabbé, Rothblat and Zheng do not teach a cell culture medium composition comprising GM-CSF and IL-10. Regarding claim 5, Crabbé, Rothblat and Zheng do not teach the recited GM-CSF, TGF-β, and IL-10 concentrations
Yu teaches a culture media composition for culturing fetal monocytes and comprising 50 ng/ml GM-CSF and 10 ng/ml hTGF-β1 (e4, 2nd full paragraph), reading on claim 4 and reading in-part on claim 5. Yu teaches methods of differentiating the fetal monocytes into alveolar macrophages (AM) with the culture media comprising GM-CSF as a survival factor and hTGF-β1 to induce AM differentiation of the monocytes (the paragraph starting on page 907 and ending on page 909, and Fig. 3), reading on claims 4 and 5.
Thomassen teaches a culture media composition for culturing human alveolar macrophages and comprising 10 ng/ml interleukin 10 (Il-10), and which significantly reduces LPS-stimulated cytokine secretion (Abstract and the table at the top of page 322), reading on claim 4 and reading in-part on claim 5.
Regarding claim 4, It would have been obvious to a person of ordinary skill in the art before the invention was filed to add the GM-CSF and TGFβ of Yu and the IL-10 of Thomassen to culture media composition of Crabbé. A person of ordinary skill in the art would have had a reasonable expectation of success to do so because Crabbé, Yu, and Thomassen are all in-part directed towards cell culture media compositions for culturing alveolar macrophages in vitro, and Crabbé and Yu are both directed towards cell culture media compositions for differentiating monocytes into alveolar macrophages in vitro. Regarding GM-CSF and TGFβ, the skilled artisan would have been motivated to do so because Yu teaches that GM-CSF acts as a survival factor and hTGF-β1 induces AM differentiation of the monocytes, and so the addition would predictably improve Crabbé’s culture media composition in Crabbé’s downstream methods of differentiating monocytes into alveolar macrophages in vitro. Regarding IL-10, the skilled artisan would have been motivated to do so because Thomassen teaches that addition of 10 ng/ml interleukin 10 (Il-10) significantly reduces LPS-stimulated cytokine secretion and so the addition would be predictably advantageous to further study cellular mechanisms of inflammation in the alveolar macrophage like cells of Crabbé.
Regarding the concentrations of claim 5, optimization within prior art conditions or through routine experimentation will generally not support patentability absent a showing of criticality of the claimed range to the contrary. See M.P.E.P. § 2144.05, particularly subsections II and III. In this case, both Yu and Thomassen teach that the GM-CSF, TGFβ, and IL-10 concentrations are known result-effect variables with respect to cell survival for GM-CSF, differentiating monocytes to alveolar macrophages for TGFβ, and reducing LPS-induced cytokine secretion for IL-10. Thus, the burden is shifted back to establish criticality of the claimed concentrations by objective evidence.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill at the time the invention was made.
Conclusion
No claims are allowed. No claims are free of the art.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SEAN C BARRON whose telephone number is (571)270-5111. The examiner can normally be reached 7:30am-3:30pm EDT/EST (M-F).
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/Sean C. Barron/Primary Examiner, Art Unit 1653
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