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 1-4 and 9-23 are pending and examined herein.
Priority
This application, filed 02/05/2024, is a 371 of PCT/EP2022/072138, filed 08/05/2022, which claims benefit of EPO 21190083.2, filed 08/06/2021. This benefit is acknowledged and the claims examined herein are treated as having an effective filing date of 08/06/2021.
Information Disclosure Statement
The Information Disclosure Statement filed 02/05/2024 is acknowledged and has 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 16 and 22 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.
Claims 16 and 22 recite “optionally comprising” followed by multiple method steps. It is unclear whether “optionally” refers to all of the following method steps or only a particular step. For purposes of compact prosecution, the all the steps following “optionally” will not be required; however, clarification is required.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-4 and 9-23 are rejected under 35 U.S.C. 101 because the claimed invention is directed to abstract ideas and to laws of nature/natural phenomena without significantly more.
The U.S. Patent and Trademark Office recently revised the MPEP with regard to§ 101 (see the MPEP at 2106). Regarding the MPEP at 2106, in determining what concept the claim is "directed to," we first look to whether the claim recites:
(1) any judicial exceptions, including certain groupings of abstract ideas (i.e., mathematical concepts, certain methods of organizing human activity such as a
fundamental economic practice, or mental processes); and
(2) additional elements that integrate the judicial exception into a practical
application (see MPEP § 2106.05(a)-(c), (e)-(h)).
Only if a claim (1) recites a judicial exception and (2) does not integrate that exception into a practical application, do we then look to whether the claim contains an "'inventive concept' sufficient to 'transform"' the claimed judicial exception into a patent-eligible application of the judicial exception. Alice, 573 U.S. at 221 (quoting Mayo, 566 U.S. at 82). In so doing, we thus consider whether the claim:
(3) adds a specific limitation beyond the judicial exception that is not "wellunderstood,
routine, conventional" in the field (see MPEP § 2106.0S(d)); or
(4) simply appends well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception. See MPEP 2106.
ELIGIBILITY STEP 2A: WHETHER A CLAIM IS DIRECTED TO A JUDICIAL EXCEPTION
Step 2A, Prong 1
Claim 1 recites “A method for relativizing a signal (1)…wherein relativizing comprises comparing signal (1) with signal (2) from a standard”. Similarly, claim 17 recites “A method for analyzing a glycan structure of a glycoprotein of interest, comprising…comparing the first signal of step a) to a second signal”. Likewise, claim 3 recites “wherein relativizing comprises comparing the signal (1)…with the signal (2)”.
The step of “comparing” is categorized as an abstract idea, namely mental processes/ concepts performed in the human mind (such as a practitioner thinking about the two claimed signals). The claims, under their broadest reasonable interpretation, cover performance of comparing the signals solely within the human mind, or by a human using a pen and paper. Comparing information regarding a sample to a control represents an abstract idea.
Further, claim 2 recites “wherein relativizing comprises (i) if signal (1) is lower than signal (2), it is indicative of…or (ii) if signal (1) is equal to or higher than signal (2), it is indicative that…”, which constitutes comparison to a threshold value, and claim 4 recites “wherein the concentration series comprises a concentration which corresponds to a predetermined threshold concentration” and claim 20 recites “wherein the first signal being lower than the second signal indicates said glycan structure is not present…or wherein the first signal being equal to or higher than the second signal indicates said glycan structure is present”. The recited thresholds also constitute abstract ideas (a threshold being itself a mathematical concept).
Similar concepts involving comparing information regarding a sample or test subject to a control or target data have been held to be an "abstract mental process", as in University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 113 USPQ2d 1241 (Fed. Cir. 2014) which involved "comparing BRCA sequences and determining the existence of alterations", the collecting and comparing of known information in Classen, the comparing information regarding a sample or test subject to a control or target data in Ambry and Myriad CAFC, as well as Mayo (which also involved specific numerical cutoff levels).
Further, claim 15 recites “The method of claim 1 wherein presence of said glycan structure (A) is indicative of cancer”.
The natural relationship to which the claims are directed (i.e., the relation between the presence of a particular glycan and cancer) is a law of nature. Similar concepts have been held by the courts to constitute law of nature/ natural phenomena, as in the identification of a correlation between the presence of in a bodily sample (such as blood or plasma) and cardiovascular disease risk in Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1361, 123 USPQ2d 1081, 1087 (Fed. Cir. 2017). In Mayo, the Supreme Court found that a claim was directed to a natural law, where the claim required administering a drug and determining the levels of a metabolite following administration, where the level of metabolite was indicative of a need to increase or decrease the dosage of the drug. See Mayo Collaborative Services v. Prometheus Labs., Inc., 566 U.S. 66, 74 (2012).
The instant claims are similar to those in Mayo as they involve a "relation itself [which] exists in principle apart from any human action" (id. at 77), namely the relationship between the naturally occurring glycan on a protein of interest and the presence of cancer.
The correlation between the presence of particular glycans and cancer is a judicial exception as it exists in principle apart from any human action; the correlation itself therefore cannot form the basis for eligibility.
Step 2A, Prong 2
The above-discussed steps of “comparing” signal (1) to signal (2) are insufficient to integrate into a practical application because steps corresponding to mental activity, which could be performed in a practitioner’s head, are insufficient to constitute a practical application.
The claims also recite “determining a glycan structure” (claim 1) and “generating a first signal from a glycoprotein of interest” (claim 17). Such steps of determining the glycan structure and generating a signal are insufficient to integrate the judicial exception(s) because the purpose is merely to obtain data. This does not go beyond insignificant presolution activity, i.e., a mere data gathering step necessary to use the correlation, similar to the fact pattern in In re Grams, 888 F.2d 835 (Fed. Cir. 1989) and Ariosa Diagnostics, Inc. v. Sequenom, Inc. (Fed. Cir. 2015). Regarding the dependent claims, claims 9, 10, 16, 18, 19, 21, 22, and 23 are all directed towards limiting the insignificant presolution activity and fail to integrate the judicial exceptions into a practical application. Likewise, claims 11 limits the glycan structure to be determined and claims 12-14 limit the protein of interest; however, these claims also fail to integrate the judicial exceptions into a practical application.
ELIGIBILITY OF STEP 2B: WHETHER THE ADDITIONAL ELEMENTS CONTRIBUTE AN “INVENTIVE CONCEPT”
Further, the additional elements of the claims (the active method steps/limitations recited in addition to the judicial exceptions themselves) do not add significantly more to the judicial exceptions.
In this case, it was well-understood, routine, and conventional to determine glycan structure on a protein of interest while using neoglycoproteins as a standard for comparison. See for example, Geuijen et al., “Label-Free Glycoprofiling with Multiplex Surface Plasmon Resonance: A Tool To Quantify Sialylation of Erythropoietin” Analytical Chem. (published 07/20/2015, referred to herein as Geuijen), who measured protein glycosylation using a BSA-based neoglycoprotein standard (see for example p. 8117, col. 2, para. 5, lines 1-7) to determine the glycosylation patterns of target proteins (see for example p. 8119, col. 2, para. 3, lines 1-4).
See also Lee et al., “Chapter 17: Neoglycoproteins” Glycoproteins II (published 1997, referred to herein as Lee) and Kuberan et al., “Preparation and isolation of neoglycoconjugates using biotin-streptavidin complexes (published 1999, referred to herein as Kuberan) which both teach the use of streptavidin-based neoglycoproteins for assays involving lectin-glycan interaction studies (see for example Lee, p. 613, section 2.7, lines 1-7) (see for example Kuberan, p. 272, col. 1, para. 1, lines 1-11).
In view of the above evidence, as well as the detailed analysis below in the rejection under 35 U.S.C. 103, determining a glycan structure by comparing two signals using a neoglycoprotein standard as the source of one signal does not add any feature that is more than well-understood, conventional, or routine in the field of glycoprotein analysis and biochemical assay methodologies.
For all of these reasons, the claims fail to include additional elements that are sufficient to either integrate the judicial exception(s) into practical application(s) thereof, or amount to significantly more than the judicial exception(s).
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, 9, 11-13, 16-17, and 20-23 are rejected under 35 U.S.C. 103 as being unpatentable over Geuijen et al., “Label-Free Glycoprofiling with Multiplex Surface Plasmon Resonance: A Tool To Quantify Sialylation of Erythropoietin” Analytical Chem. (published 07/20/2015, referred to herein as Geuijen) in view of Lee et al., “Chapter 17: Neoglycoproteins” Glycoproteins II (published 1997, referred to herein as Lee) as evidenced by Mintz et al., “Discovery and horizontal follow-up of an autoantibody signature in human prostate cancer” PNAS (published 02/24/2015, referred to herein as Mintz).
Regardings claims 1-2, 17, 20, and 22, Geuijen teaches a method for relativizing a signal obtaining from determining a glycan structure on a protein of interest, i.e. fetuin or transferrin (p. 8119, col. 2, para. 3, lines 1-9), with a signal obtained from glycan structure on a neoglycoprotein standard (p. 8117, col. 2, para. 5, lines 5-7). Geuijen teaches that the neoglycoproteins act as “model compounds” (p. 8117, col. 2, para. 5, lines 5-7) and the results of fetuin or transferrin analysis are compared to the neoglycoprotein results (p. 8119, col. 2, para. 3, lines 1-9).
However, Geuijen does not teach the use of a neoglycoprotein comprising streptavidin bound through biotin-streptavidin interaction to at least one pre-defined glycan.
Regarding claims 1 and 17, Lee teaches the use of neoglycoproteins for assays involving carbohydrate-lectin interactions (p. 614, Section 4.1, lines 1-8). Lee teaches neoglycoproteins comprising streptavidin bound to glycans are an alternative to BSA-based neoglycoproteins (p. 613, section 2.7, lines 1-7) with the advantage of having structurally-defined attachment sites.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the BSA-based neoglycoproteins used in the method taught by Geuijen with streptavidin-based neoglycoproteins as taught by Lee. An artisan would have been motivated to make this substitution because, as taught by Lee, streptavidin-based neoglycoproteins have the advantage of having well-defined attachment sites for the glycans, which would reduce the heterogeneity with the neoglycoproteins used. An artisan would have a reasonable expectation of success in making this substitution because, as taught by Lee, both BSA and streptavidin-based neoglycoproteins are usable in assays involving carbohydrate-lectin interactions, such as the method taught by Geuijen.
Regarding claims 3 and 4, Geuijen teaches determining a concentration series of the glycan structure on the neoglycoprotein (p. 8118, col. 1, para. 1, lines 1-4) up to 10µM, which is higher than known binding fucose at 10nM (p. 8118, col. 2, para. 1, lines 9-11).
Regarding claim 9, Geuijen teaches measuring signal intensities (p. 8119, col. 2, para. 3, lines 4-7).
Regarding claim 11, Geuijen teaches measuring core fucose (p. 8120, col. 1, para. 3, lines 1-6).
Regarding claims 12 and 13, Geuijen teaches measuring fetuin (p. 8119, col. 2, para. 3, lines 1-4), which is a prostate cancer biomarker, as evidenced by Mintz (Abstract, lines 10-14).
Regarding claims 16, Geuijen teaches generating a signal to determine the glycan structure by binding the neoglycoprotein (p. 8117, col. 2, para. 5, lines 1-9) or the protein of interest (p. 8119, col. 2, para. 3, lines 1-4) with a lectin to form a complex.
Regarding claims 21 and 23, Geuijen teaches generating a plurality of signals using a plurality of neoglycoproteins with various amounts of glycans as a concentration series (Figure 1, p. 8118, col. 1, para. 1, lines 1-4).
Claims 10, 18, and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Geuijen in view of Lee as applied to claim 1 above, and further in view of US 2011/0129938 A1, “L-FUCOSE ALPHA1-6 SPECIFIC LECTIN” (published 06/02/2011, referred to herein as ‘938).
The teachings of Geuijen in view of Lee as applied to claim 1 above are incorporated herein.
Regarding claims 10, 18, and 19, Geuijen teaches a method of detecting glycan structure comprising SPR (p. 8117, col. 2, para. 5, lines 1-9).
However, Geuijen in view of Lee does not teach the use of an enzyme-linked method for glycan detection.
Regarding claims 10, 18, and 19, ‘938 teaches the use of surface plasmon resonance and enzyme-linked immunosorbent assays as interchangeable methods for glycan detection (para. 0130, lines 1-6). ‘938 teaches that the enzyme-linked immunosorbent assay comprises associating an enzyme with a glycoprotein-enzyme complex via indirect binding to the glycan, and reacting a substrate with the enzyme to generate a signal (para. 0195, lines 9-20).
It would have been obvious to one of skill in the art before the effective filing date of the claimed invention to substitute the SPR assay taught by Geuijen in view of Lee with the ELISA assay taught by ‘938. Doing so is considered to be a mere Simple Substitution of One Known Element for Another to Obtain Predictable Results (See MPEP 2043(I)(B)). An artisan would recognize that, as taught by Lee, both SPR and ELISA are known methods for the predictable detection of glycans.
Claims 14 and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Geuijen in view of Lee as applied to claims 1, 12, and 13 above, and further in view of Llop et al., “Improvement of Prostate Cancer Diagnosis by Detecting PSA Glycosylation-Specific Changes” Theranostics (published 05/24/2016, referred to herein as Llop).
The teachings of Geuijen in view of Lee as applied to claims 1, 12, and 13 above are incorporated herein.
Regarding claims 14 and 15, Geuijen teaches detecting fetuin as a protein of interest (p. 8119, col. 2, para. 3, lines 1-4), which is a prostate cancer biomarker. Geuijen teaches that the method is usable for rapid glycosylation fingerprinting to determine glycan moieties (p. 8121, col. 1, para. 3, lines 1-7).
However, Geuijen in view of Lee does not teach detecting prostate cancer biomarker proteins β-haptoglobin, TIMP-1, PSA, fPSA, or tPSA.
Llop teaches the determination of PSA glycosylation patterns is useful for the diagnosis of prostate cancer (p. 1203, col. 1, para. 1, lines 7-20).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use the method taught by Geuijen in view of Lee to measure PSA glycosylation, as taught by Llop. An artisan would have been motivated to do so in order to facilitate the diagnosis of prostate cancer, as taught by Llop. An artisan would have had a reasonable expectation of success in measuring PSA glycosylating with the method taught by Geuijen in view of Lee because PSA glycosylation comprises fucose and sialic acid, which are both glycans measured in the method taught by Geuijen on glycoproteins.
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 July 29, 2026
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