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 .
Status of the Claims
Claims 1 and 3-21 are pending and examined herein.
Priority
This application, filed 04/20/2023, is a 371 of PCT/EP2021/082154, filed 11/18/2021, which claims benefit to EP20208703.7, filed 11/19/2020. This priority is acknowledged and the claims examined herein are treated as having an effective filing date of 11/19/2020.
Information Disclosure Statement
The Information Disclosure Statements filed 4/20/2023, 4/10/2025, and 4/10/2025 are acknowledged and have been considered.
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 4-6, 8-10, 12-14, and 16-19 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.
Regarding claims 4-6, 8-10, 12-14, and 16-19, the phrases "preferably", “optionally”, and “e.g.” renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim Rejections - 35 USC § 103
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.
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.
Claims 1, 4-13, 15, and 16 are rejected under 35 U.S.C. 103 as being unpatentable over EP 1672366 A2, “Methods and compositions for opsonophagocytic assays” (published 06/21/2006, referred to herein as Martinez) in view of “Normal polyclonal immunoglobulins (‘IVIg’) inhibit microglial phagocytosis in vitro” Journal of Neuroimm. (published 05/15/2000, referred to herein as Stangel) as evidenced by “Sandoglobulin NF Liquid” by CSL Behring Canada, Inc (published 02/15/07, referred to herein as CSL).
Regarding claim 1, Martinez teaches a method for testing the potency of an immunoglobulin composition comprising providing a bead coated with an antigen (para. 0012, lines 3-6), an antibody specifically bound to said antigen (para. 0012, lines 6-9), contacting an immune effector cell (para. 0012, lines 9-11), and determining effector cell function, i.e. opsonophagocytic function (para. 0016, lines 1-3).
Regarding claim 4, Martinez teaches that the antibody specifically bound to said antigen is an antibody from a patient sample who has been infected with a pathogen (para. 0031, lines 1-4).
Regarding claim 5, Martinez teaches the use of latex beads (para. 0029, lines 20-22).
Regarding claim 6, Martinez teaches coating the bead with the antigen by incubating the bead with the antigen (para. 0048, lines 3-6).
Regarding claim 7, Martinez teaches preparing the bead coated with the antigen and an antibody by incubating the bead coated with the antigen with antibodies to said antigen (para. 0040, lines 1-3).
Regarding claim 11, Martinez teaches comparing effector cell function to a test carried out without contacting the bead coated with the antigen and antibody (para. 0039, example 2 “beads without test sera”). In this embodiment, Martinez teaches comparing effector cell function with a test that contacts the effector cell with a bead coated only with the antigen.
Regarding claim 12, Martinez teaches that the effector cell can be macrophages, monocytes, neutrophils, eosinophils, or any cell that expresses an Fc receptor, preferably HL-60 cells (para. 0025, lines 6-13).
Regarding claim 13, Martinez teaches measuring phagocytosis of the beads as the effector cell function (para. 0016, lines 1-3).
However, Martinez does not teach a method for testing immunomodulatory (claim 15) potency of an immunoglobulin test composition comprising contacting said bead with an immunoglobulin test composition (claim 1) wherein the immunoglobulin test composition is polyclonal (claim 8) derived from a plurality of human (claim 9) plasma or serum (claim 10).
Regarding claims 1 and 15, Stangel teaches a method of testing the immunomodulatory potency of a polyclonal immunoglobulin test composition, “IVIg” (p. 139, col. 1, para. 3). Stangel teaches adding IVIg to a sample (p. 139, col. 1, para. 3, lines 8-12) before measuring the phagocytosis on antibody-bound RBCs (p. 139, col. 1, para. 3, lines 3-7) by effector cells (p. 139, col. 1, para. 3, lines 9-12) in order to determine the immunomodulatory effect of IVIg on effector cell activation, i.e. Fc receptor-mediated phagocytosis (p. 140, col. 2, para. 1, lines 1-3).
Regarding claim 8, Stangel teaches that IVIg is polyclonal (Title).
Regarding claim 9, Stangel teaches the use of Sandoglobulin IVIg (p. 138, col. 1, para. 2, lines 5-6), which is a derived from a plurality of human donors, as evidenced by CSL (p. 13, lines 10-11). However, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to perform routine optimization concentration of the components in the claimed invention to make and use the claimed invention. As noted in In re Aller, 105 USPQ 233 at 235, more particularly, where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. Routine optimization is not considered inventive and no evidence has been presented that arriving at the claimed concentration of immunoglobulins was anything other than routine, that the properties of the concentration of immunoglobulins from the optimization has any unexpected properties, or that the results should be considered unexpected in any way as compared to the closest prior art. Optimization of parameters is a routine practice that would be obvious for the artisan to employ. See MPEP § 2144.05. The artisan would have had a reasonable expectation of success based on the cumulative disclosure of Stangel. Stangel teaches the use of immunoglobulin test compositions of 10 and 20 mg/ml (g/L) which has a dose-dependent effect on phagocytosis (Figure 5). Additionally, Sandoglobulin used by Stangel is provided at an immunoglobulin concentration of 120 g/L, as evidenced by CSL (p. 17, para. 1, lines 1-2), supporting that optimizing the concentration of immunoglobulin for use in the assay is routine.
Regarding claim 10, Stangel teaches the use of Sandoglobulin IVIg (p. 138, col. 1, para. 2, lines 5-6), which is a derived from plasma, as evidenced by CSL (p. 13, lines 10-11).
Regarding claim 16, Stangel teaches that inhibition of effector cell function is correlated to potency of IVIg (Figure 5, p. 140, col. 1, para. 1, lines 1-3).
It would have been obvious to one of ordinary skill before the effective filing date of the claimed invention to modify the method taught by Martinez to include the step of adding IVIg as taught by Stangel. An artisan would have been motivated to make this modification in order to study the effects of IVIg on effector cell function which is an important consideration for the use of IVIg to treat inflammation-related disorders, as taught by Stangel (p. 137, col. 2, para. 2, lines 1-10). An artisan would have a reasonable expectation of success in making this modification because Stangel has shown that the addition of IVIg to assays measuring Fc receptor-mediated phagocytosis is useful to detecting the immunomodulatory effect of IVIg. An artisan would recognize that the effect of IVIg on Fc receptor-mediated phagocytosis could be measured in any Fc receptor-expressing cell type, not only in microglia used in Stangel.
Claims 3, 20, and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Martinez in view of Stangel as applied to claim 1 above, and further in view of Fu et al., “Understanding SARS-CoV-2-Mediated Inflammatory Responses: From Mechanisms to Potential Therapeutic Tools” Virologica Sinica (published 03/03/2020, referred to herein as Fu).
The teachings of Martinez in view of Stangel, as described above regarding claim 1, are incorporated herein.
Regarding claims 3, 20, and 21, Martinez teaches that any antigen can be attached to the beads (para. 0032, lines 6-10).
However, Martinez in view of Stangel does not teach that the antigen is SARS-CoV-2 spike protein.
Regarding claims 3, 20, and 21, Fu teaches that immune inflammatory responses to SARS-CoV-19 infection are mediated through binding of anti-spike protein antibody/spike protein complexes to the Fc receptors on monocytes and macrophages (Figure 1 “Secondary inflammatory responses”, p. 269, col. 1, para. 2, lines 8-11). Fu teaches that IVIG treatment could be used to inhibit the inflammatory response caused by the binding of anti-spike protein antibody/spike protein complexes to the Fc receptors (p. 269, col. 2, para. 2, line 22 – p. 270, col. 1, para. 1, line 2).
It would have been obvious to one of ordinary skill in the art to modify the method taught by Martinez in view of Stangel by using SARS-CoV-2 spike protein as the antigen on the beads. An artisan would have been motivated to use the spike protein in order to characterize the effect of IVIG on the inhibition of the inflammatory response caused by the binding of anti-spike protein antibody/spike protein complexes to the Fc receptors, as taught by Fu. An artisan would have a reasonable expectation of success in making this modification because as taught by Martinez, any antigen could be attached to the beads, and, as taught by Fu, IVIG could be used as a potential treatment to inhibit the inflammatory response caused by the binding of anti-spike protein antibody/spike protein complexes to the Fc receptors.
Claim 14 is rejected under 35 U.S.C. 103 as being unpatentable over Martinez in view of Stangel as applied to claims 1 above, and further in view of Jayne et al., “Intravenous immunoglobulin as immuno-modifying treatment” Disease-modifying Therapy in Vasculitides (published 2001, referred to herein as Jayne).
The teachings of Martinez in view of Stangel, as described above regarding claim 1, are incorporated herein.
Regarding claim 14, Stangel teaches a method to determine the immunomodulatory effect of IVIg on Fc receptor-mediated effector cell activation (p. 140, col. 2, para. 1, lines 1-3).
However, Martinez in view of Stangel do not teach measuring IL-8 production.
Jayne teaches that IVIG has an immunomodulating effect on IL-8 production by effector cells by affecting binding of the Fc region (p. 100, para. 1, lines 11-15).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method taught by Martinez in view of Stangel by measuring IL-8. An artisan would have been motivated to make this change in order to characterize the Fc-dependent increase in IL-8 after IVIG treatment, as taught by Jayne. An artisan would have a reasonable expectation of success in making this change because IVIG treatment is known to have an immunomodulatory effect on IL-8 production and methods of detecting IL-8 are considered routine in the art of in vitro biochemical assays.
Claims 17 and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Martinez in view of Stangel as applied to claim 1 above, and further in view of Radosevich et al., “Intravenous immunoglobulin G: trends in production methods, quality control and quality assurance.” Vox Sanguinis (published 07/29/2009, referred to herein as Radosevich).
The teachings of Martinez in view of Stangel, as described above regarding claim 1, are incorporated herein.
Regarding claims 17 and 18, Martinez in view of Stangel teach the method of testing the potency of an immunoglobulin test composition of claim 1.
However, Martinez in view of Stangel does not teach comparing the potency of the test composition to a standard composition (claim 17) or a method for preparing a standardized immunoglobulin composition (claim 18).
Regarding claims 17 and 18, Radosevich teaches a method for preparing a standardized immunoglobulin composition (IVIG, Figure 2) comprising at least 30 g/L immunoglobulin (p. 18, col. 1, para. 2, lines 8-10). Radosevich teaches the method steps of pooling plasma or serum from a plurality of donors (Figure 2, “Plasma Pool”, p. 12, col. 1, para. 1, lines 6-8), isolating (p. 13, col. 2, para. 2, lines 1-2) and concentrating immunoglobulins (Figure 2, “Concentration”, p. 18, col. 1, para. 2, lines 8-10). Radosevich teaches testing the potency of the test composition against a standard immunoglobulin composition, i.e. WHO reference preparations, wherein the composition is discarded if the potency is not in a predetermined range, i.e. “Batches should comply with the quality specifications defined in the marketing authorization file of each product” (Assay ranges presented in Table 2, p. 21, col. 2, para. 1, lines 1-17). Radosevich teaches that methods for “product testing should be designed and validated for optimal performance and consistency” and “a number of additional assays, not used for routine quality control, can be very helpful at the development stage” (p. 23, col. 2, para. 1, lines 1-7).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate the method for testing potency of an immunoglobulin test composition taught by Martinez in view of Stangel into the method for producing a standardized immunoglobulin composition as taught by Radosevich. An artisan would be motivated to make this modification in order to ensure that batches of pooled immunoglobulin compositions have consistent immunomodulatory effects on Fc-receptor mediated inflammation. As taught by Stangel, the immunomodulatory effect of these compositions impacts their use for the treatment of inflammation-related conditions (Stangel, Abstract, p. 137, col. 2, para. 2, lines 1-14). An artisan would have a reasonable expectation of success making this modification because, as taught by Radosevich, a variety of assays can be useful for the testing, optimization, and development of pooled immunoglobulin compositions with consistent performance.
Claim 19 is rejected under 35 U.S.C. 103 as being unpatentable over Martinez in view of US 4,208,479, “Label modified immunoassays” (published 06/17/1980, referred to herein as Zuk).
If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction. In order words, a recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. See MPEP 2111.02 II. In this case, “for carrying out the method of claim 1” is not considered a limitation.
Regarding claim 19, Martinez teaches an immunoassay method comprising a bead (para. 0046, line 1), an antigen (para. 0046, line 10-11), an antibody (para. 0057, line 5), and a standard immunoglobulin composition with at 60 g/L immunoglobulin (para. 0059, lines 1-6). Martinez uses the Sandoglobulin standard immunoglobulin composition at 6% concentration, which is equal to 60 g/L as evidenced by CSL (p. 17, para. 1, lines 1-2, 12% is 120 g/L).
However, Martinez does not teach these assay components in a single kit.
Regarding claim 14, Zuk teaches that in performing assays, it is convenient to combine the necessary reagents together in a kit (column 22, lines 20-68 in particular). Zuk further teaches that this may improve assay accuracy.
It would have been obvious to one of ordinary skill in the art to provide the components of the assay taught by Martinez together in kit form for convenience and accuracy as taught by Zuk.
Conclusion
No claims are allowable.
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/C.E./Examiner, Art Unit 1677
/BAO-THUY L NGUYEN/Supervisory Patent Examiner, Art Unit 1677 January 22, 2026