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 .
FINAL ACTION
Amendment Entry
1. Applicant’s response to the Non-Final Action dated 9/10/25 is acknowledged (reply filed 12/22/25). In the amendment filed therein claims 38, 42, and 46 were modified. While new claims 57-65 were added. Claims 1-37, 39-41, 51, and 53-56 are canceled without prejudice or disclaimer.
2. Claims 46-50 and 52 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 6/4/25. Currently claims 38, 42-45, and 57-65 are under consideration.
3. Rejections and/or objections of record not reiterated herein have been withdrawn. The amended claims and newly submitted claims have rendered the rejections MOOT.
Priority
4. This application is a 371 of PCT/IL2020/050676 filed 6/17/2020, which claims priority to US provisional application no. 62/862,728 filed on June 18, 2019. The application has a priority dated of June 18, 2019.
NEW GROUNDS OF REJECTIONS NECESSITATED BY AMENDMENTS
Claim Objections
5. Claim 61 is objected to because of the following informalities: Claim 61 is dependent on claim 61. It appears that Applicant intended to depend on claim 60.
6. Claims 42, 58, and 63 are objected to because of the following informalities: The claims do not consistently utilize the appropriate indicators. In claim 42 – (i) is missing. In claims 58 and 63 – (a), (i), and (ii) are missing.
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.
7. Claims 38, 42-45, and 57-65 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 pre-AIA the applicant regards as the invention.
A. Claims 38, 57, and 62 are vague and indefinite because it is not clear as to what Applicant intends by a N-glycolyIneuraminic acid (Neu5Gc) related disease or disorder. As recited it is not clear what the claims will encompass. The specification discloses that “the Neu5Gc related disease or disorder is selected from atherosclerotic cardiac disease, cancer and chronic inflammatory conditions. According to some embodiments, the Neu5Gc related disease is cancer. According to some embodiments, cancer is carcinoma.
According to one embodiment, the cancer is selected from gastric, colorectal, pancreatic, prostate, oral, esophageal, small intestinal, hepatic, ovarian, endometrial, and breast cancer. According to one embodiment, the cancer is selected from colorectal cancer and breast cancer. According to one embodiment, the cancer is colorectal cancer. According to another embodiment, the cancer is breast cancer.” See page 16 lines 24-31.
By way of example the claimed method appears to only be tested in Example 1 page 22 lines 24-31, investigates health and diseases (e.g. cancer, cardiovascular diseases, metabolic syndrome, rheumatoid arthritis and hypertension). However, the scope of the claims as written is ambiguous. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). As written the claimed method is unclear as to what is meant by a Neu5Gc disease or disorder. As recited the metes and bounds of the claims cannot be determined. It is suggested that the actual Neu5Gc diseases and/or disorders are listed in the claims in order to obviate the rejection. Appropriate correction is required.
B. Claims 57 and 62 are vague and indefinite in reciting “prevention”. The term “prevention” in claims 57 and 62 is a relative term which renders the claim indefinite. The term is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. It is suggested that the term in omitted in order to obviate the rejection.
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.
8. Claims 38, 42-45, and 57-65 are rejected under 35 U.S.C. 101 because the claimed invention is not directed to patent eligible subject matter.
Based upon an analysis with respect to the claims as a whole, the claims are determined to be directed to a law of nature/natural principle. The rationale for this determination is explained below:
Claims are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more.
The claims are directed to a judicial exception, wherein, sets of anti-Neu5Gc antibodies are measured in a sample from a subject. However, anti-N-glycolylneuraminic acid (Neu5Gc)-sialylated glycan antibodies are a naturally occurring products. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the steps in addition to measuring an anti-N-glycolylneuraminic acid (Neu5Gc)-sialylated glycan antibody are steps for routine data gathering in order to test for the correlation (ratio of naturally occurring products such as antibodies against Neu5Gc 2,3 linked glycans as compared to antibodies against Neu5Gc 2,6 linked glycans as taught in the specification on page 9 lines 8-12 for example) do not add a meaningful limitation to the method as they would be routinely used by those of ordinary skill in the art in order to apply the correlation.
The steps in addition to anti N- glycolylneuraminic acid (Neu5Gc)-sialylated glycan antibody detection are steps of obtaining a biological sample from the subject and determining the level of antibodies that binds to the N- glycolylneuraminic acid (Neu5Gc)-sialylated glycan in said biological sample, which were well understood and routine in the art before the effective filing date of the instant application as demonstrated by Amon et al. (Oncotarget, 2017, Vol.8, No.68, pages 112236-112244).
A claim that focuses on use of a natural principle (method/process) must also include additional elements or steps to show that the inventor has practically applied, or added something significant to, the natural principle itself. See Mayo, 101 USPQ2d at 1966.
To show integration, the additional elements or steps must relate to the natural principle in a significant way to impose a meaningful limit on the claim scope. The analysis turns on whether the claim has added enough to show a practical application. See id. at 1968.
In other words, the claim cannot cover the natural principle itself such that it is effectively standing alone. A bare statement of a naturally occurring correlation, albeit a newly discovered natural correlation or very narrowly confined correlation, would fail this inquiry. See id. at 1965, 1971.
It is not necessary that every recited element or step integrate or relate to the natural principle as long as it is applied in some practical manner. However, there must be at least one additional element or step that applies, relies on or uses the natural principle so that the claim amounts to significantly more than the natural principle itself.
Along with integration, the additional steps must be sufficient to ensure that the claim amounts to significantly more than the natural principle itself by including one or more elements or steps that limit the scope of the claim and do more than generally describe the natural principle with generalized instructions to “apply it.” See id. at 1965, 1968. The additional elements or steps must narrow the scope of the claim such that others are not foreclosed from using the natural principle (a basic tool of scientific and technological work) for future innovation.
Elements or steps that are well-understood, purely conventional, and routinely taken by others in order to apply the natural principle, or that only limit the use to a particular technological environment (field-of-use), would not be sufficiently specific. See id. at 1968.
In the present case, the claims are directed to a naturally occurring correlation, namely the naturally occurring measurement of known antibodies in a sample. See especially claims 38, 57,and 62 wherein a set of antibodies are measured and a calculated ratio is determined for analysis. These claims read on naturally occurring antibodies (Neu5Gcα 2,3 linked glycans and Neu5Gcα 2,6 linked glycans) because no specific antibodies sets are recited in the claim language.
In addition, the naturally occurring determination of antibodies in the sample are utilized to assess disease or disease risk (i.e. cancer and/or cancer treatment).
However, the combination of steps recited in the claims, taken as a whole, is not sufficient to qualify as a patent-eligible practical application because the steps are not sufficiently specific to ensure that the claims amount to significantly more than the natural principle itself. Rather, in this case the claims would cover every substantial practical application of the correlation.
In particular, the “comparing and calculating” step is recited at a high level of generality and is not sufficient to ensure that the claims amount to significantly more than the naturally occurring correlation itself. This is because every application of the correlation would require determining anti-Neu5Gc antibodies in a sample (blood, plasma, urine, etc.); and also because the “evaluation and calculating” appear to be drawn to mental processes resulting in a comparing (conclusion)” step does not relate to the natural principle in a significant way to impose a meaningful limit on the claim scope (for example, the claims are not limited to any particular testing technique that is not well-understood, routine, or conventional). Therefore claim(s) 38, 42-45, and 57-65 are also directed to abstract ideas as independent claim 38, 57, and 62 do not include any wet steps to conduct the process (evaluating – calculating a ratio and comparing). Therein the step amounts to comparing and reaching a conclusion or assessing the measurements. Comparing information regarding a sample or test subject to a control or target data (reference) reads on “An Idea ‘Of Itself’” as when given its broadest reasonable interpretation, such a comparison would read on a mental process that could be performed in the human mind, or by a human using pen and paper.
Similar mental processes have been held by the courts to be abstract ideas, e.g., collecting and comparing known information in Classen, or comparing information regarding a sample or test subject to a control or target data in Ambry and Myriad CAFC. The specific information that is being compared (in this case, biomarkers or metabolite levels to particular reference(s) levels) merely narrows the abstract idea, which does not make the comparison step less abstract and is not sufficient to provide eligibility on its own.
The analysis is to be used for evaluating whether a claim is drawn to patent-eligible subject matter.
Step 1 determines whether the claim is directed to a process, machine, manufacture, or composition of matter. If the claim is directed to a statutory category, proceed to Step 2.
Step 2 is the two-part analysis from Alice Corp. (also called the Mayo test) for claims directed to laws of nature, natural phenomena, and abstract ideas (the judicially recognized exceptions).
In Step 2A, Prong 1 determine whether the claim is directed to a law of nature, a natural phenomenon, or an abstract idea enumerated in the 2019 PEG (judicial exceptions) and
Step 2A, Prong 2 determine whether the claim recites additional elements that integrate the exception into a practical application of the exception
If the exception is not integrated into a practical application, then proceed to Step 2B determines whether the claim as a whole, amounts to significantly more than the exception.Analysis of Claims 38, 57, and 62:
I. The present claims are directed to a process so Step 1 is satisfied.
II. The present claims are directed to judicial exceptions? Wherein mental processes are utilized at least in claim 1 (detecting, calculating ratios, comparing, and determining biomarkers in a patient sample as an indicator for Neu5Gc disease/disorder); therein reducing Neu5Gc intake. The methods are drawn to a natural phenomenon (JE). And this judicial exception includes mental processes - concepts performed in the human mind (including an observation, evaluation, judgment, opinion). Therefore, step 2A Prong 1 and Prong 2 is satisfied.
Claims 38, 42-45, and 57-65 are directed to an abstract idea that is not integrated into a practical application (the JE is not integrated into a practical application).
The scope of claims 38, 57,and 62 encompasses embodiments where the biomarker (Neu5Gc ratios above 0.9) are not present at higher than controls values. Therein making the method of treatment in operable and further not integrating the JE (mental comparison) into to the claimed methods. (determining, calculating, and comparing for presence can result in detection or non-detection of the biomarker- Neu5Gc levels).
The recited abstract ideas are insufficient to make an otherwise ineligible claim patent eligible without significantly more recited in the claim. The detecting/determining/comparing step can be done by merely reviewing the data mentally and mentally making a determination. See Bilski V. Kappos 95 USPQ2d 1001 (2010). Additionally, see Mayo Collaborative Services v. Prometheus Laboratories Inc. 101 USPQ2d 1961 (2012) at 1965, quoting Gottschalkv. Benson, 409 U.S. 63, 67 [175 USPQ 673] (1972).
("Phenomena of nature, though just discovered, mental processes, and abstract intellectual concepts are not patentable, as they are the basic tools of scientific and technological work."). Furthermore, the method of “detecting, calculating, comparing, determining, and reducing” does not actually require an active step of treatment but encompasses abstract ideas and are insufficient to make an otherwise ineligible claims patent eligible, the claims are ineligible subject matter under 35 U.S.C. 101. (Alice Corporation Pty. Ltd. v. CLS Bank International, et al.).
III. Step 2B, is to determine whether the claim as a whole amount to significantly more than the exception. The active method steps of claims 38, 57, and 62 are detecting, calculating, comparing, determining and reducing Neu5Gc intake.
All of the additional claim elements listed are well-understood, routine, and conventional in this art. The active method steps of the present claims are conventional, well understood and routine.
These steps are the activities that a scientist would have relied upon to achieve the goals of the invention. The steps are interpreted as being drawn to mental steps and/or computer-implemented abstract ideas and are insufficient to make an otherwise ineligible claims patent eligible, the claims are ineligible subject matter under 35 U.S.C. 101. (Alice Corporation Pty. Ltd. v. CLS Bank International, et al).
In the present claims there are no other active method steps that transform the process into an inventive application.
In sum, when the relevant factors are analyzed, they weigh against the present claim amounting to significantly more than the judicial exceptions themselves. Accordingly, the claims do not qualify as eligible subject matter.
The subject matter which courts have found to be outside of, or exceptions to, the four statutory categories of invention is limited to abstract ideas, laws of nature and physical phenomena. Bilski v. Kappos, 561 U.S. ___, ___, 130 S. Ct. 3218, 3225, 95 USPQ2d 1001, ___ (2010) (citing Diamond v. Chakrabarty, 447 U.S. 303, 309, 206 USPQ 193, 197 (1980)). While this is easily stated, determining whether an applicant is seeking to patent an abstract idea, a law of nature or a physical phenomenon has proven to be challenging.
These three exclusions recognize that subject matter that is not a practical application of an idea, a law of nature or a physical phenomenon is not patentable. See, e.g., Rubber-Tip Pencil Co. v. Howard, 87 U.S. (20 Wall.) 498, 507 (1874) (“idea of itself is not patentable, but a new device by which it may be made practically useful is”);
Mackay Radio & Telegraph Co. v. Radio Corp. of America, 306 U.S. 86, 94, 40 USPQ 199, 202 (1939) (“While a scientific truth, or the mathematical expression of it, is not patentable invention, a novel and useful structure created with the aid of knowledge of scientific truth may be.”).
The courts have also held that a claim may not preempt abstract ideas, laws of nature or physical phenomena; i.e., one may not patent every “substantial practical application” of an abstract idea, law of nature or physical phenomenon. This is because such a patent would “in practical effect be a patent on the [abstract idea, law of nature or physical phenomenon] itself. ”Gottschalk v. Benson, 409 U.S. 63, 71-72, 175 USPQ 673, 676 (1972).
The concern over preemption was expressed as early as 1852. See Le Roy v. Tatham, 55 U.S. 156, 175 (1852) (“A principle, in the abstract, is a fundamental truth; an original cause; a motive; these cannot be patented, as no one can claim in either of them an exclusive right.”).
Examiners are reminded that 35 U.S.C. 101 is not the sole tool for determining patentability; where a claim encompasses an abstract idea, 35 U.S.C. 112, 35 U.S.C. 102 , and 35 U.S.C. 103 will provide additional tools for ensuring that the claim meets the conditions for patentability. As the Court made clear in Bilski:
Accordingly, to the reasons set forth above, claims 38, 42-45, and 57-65 are ineligible. Also, see Alice v. CLS Bank.
In summary, the claims do not include additional elements/steps or a combination of elements/steps that are sufficient to ensure that the claims amount to significantly more than a natural principle itself. This is because (1) the claims would cover every substantial practical application of the correlation and (2) the additional steps recited in the claim were previously taken by those in the field.
When the claims are considered as a whole, the steps taken together amount to no more than recognizing the law of nature itself.
A claim setting forth the relationship between known antibody measurements would require additional steps that do significantly more to apply this principle than conventional testing or general diagnostic activity based on such testing. Such additional steps could involve, for example, a testing technique or treatment steps that would not be conventional or routine.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
9. Claims 38, 42-45, and 57-65 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AlA), first paragraph, as failing to comply with the enablement requirement.
The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Specifically, the method claims recite an association of Neu5Gc related diseases and/or disorders with the measurement of Neu5Gcα 2,3 linked glycan sets and Neu5Gcα 2,6 linked glycan sets ratios. However, it is noted that all of the biomarkers (Neu5Gcα antibodies) recited in the claims are naturally occurring in at least part of the human body at some time or another, and it is therefore not reasonably possible to determine Neu5Gc related diseases or disorders thereof by merely determining the presence of the glycan combination-ratio (claims 38, 57, and 62) in the claim as written. Even the addition of a control sample and/or limiting the sample to be one of blood, serum, plasma, urine, etc. cannot be seen as significantly limiting the claims so as to enable diagnosing/association of any and all Neu5Gc related diseases and/or disorders. .
The standard for determining whether the specification meets the enablement
requirement was cast in the Supreme Court decision of Minerals Separation Lid. v. Hyde, 242 U.S. 261, 270 (1916) which postured the question: is the experimentation
needed to practice the invention undue or unreasonable? That standard is still the one
to be applied. /n re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988).
Accordingly, even though the statute does not use the term "undue experimentation," it
has been interpreted to require that the claimed invention be enabled so that any
person skilled in the art can make and use the invention without undue
experimentation. In re Wands, 858 F.2d at 737, 8 USPQ2d at 1404 (Fed. Cir. 1988).
See also United States v. Telectronics, Inc., 857 F.2d 778, 785, 8 USPQ2d 1217, 1223
(Fed. Cir. 1988) ("The test of enablement is whether one reasonably skilled in the art
could make or use the invention from the disclosures in the patent coupled with
information known in the art without undue experimentation.").
Factors to be considered in determining whether undue experimentation is
required are summarized in In re Wands (858 F.2d 731, 737, 8 USPQ2d 1400, 1404
(Fed. Cir. 1988) and MPEP 2164.01(A)) as follows: 1) quantity of experimentation
necessary, 2) the amount of direction or guidance presented, 3) the presence and
absence of working examples, 4) the nature of the invention, 5) the state of prior art, 6)
the relative skill of those in the art, 7) the predictability or unpredictability of the art, and
8) the breath of the claims. While all the above factors have been fully considered and
have led the Examiner to conclude that the specification fails to teach how to make
and/or use the claimed invention without undue experimentation, only the most relevant
factors are addressed in detail below.
(1 and 2) The breadth of the claims and the nature of the invention. The claims are broad enough to encompass embodiments wherein it is reasonably and fully expected that at least some of the biomarkers are present at some times in at least some portions of a human body, independent of whether that person has a Neu5Gc disease or disorder. See specification - Table 5. Further, the claim scope is such that one skilled in the art would not clearly understand what will be considered a Neu5Gc related disease or disorder.
(3 and 5) The state of the prior art and the level of predictability in the art: The state of the prior art of measuring known Neu5Gc levels was reasonably routine and conventional at the time of the invention, however, the association of the mere presence of a biomarker ratio at any time in any recited type of sample with a Neu5Gc associated/related disease or disorder was not at all predictable, at least because most or all of the biomarkers in the claims are naturally occurring and their mere presence (at any measurable level) in a generic sample was not known to be correlated to all Neu5Gc related diseases or disorders. In support of this, the specification at Table 1 wherein multiple glycans were tested but not all were found significant in the claimed method. “The biological mechanisms behind dietary Neu5Gc related diseases or disorders are unknown and there are few, if any, biomarkers that provide a reliable indication of this condition.” Therefore, the level of one or ordinary skill: The level of skill would be high, most likely at the Ph.D. level or equivalent number of years of experience. However, such persons of ordinary skill in this art, given its unpredictability, would have to engage in undue (non-routine) trial and error experimentation to carry out the invention as claimed.
(6 and 7) The amount of direction or guidance presented and the
existence of working examples. The present disclosure as filed does not appear to only given sufficient guidance by way of an Example, wherein quantified levels of the core group eu5Gc specific biomarker sets were required to allowing for optimal discrimination of Neu5Gc ratios vs. normal control for Neu5Gc related diseases or disorders. No guidance is given for using the full scope of the claims, such as measuring any of the biomarkers in the claims or tables of the disclosure, measuring in samples, measuring only presence rather than quantity-ratios.
(8) The quantity of experimentation required to practice the claimed
invention based on the teachings of the specification. Therefore, it is deemed that further research of an unpredictable nature would be necessary to make or use the invention as claimed.
Thus, due to the inadequacies of the instant disclosure, undue experimentation would be required of one of skill in the art to practice the full scope of the claimed invention.
Furthermore, from the specification in Example 9 the ratio parameter between quarter evaluations (Q1, Q2, Q3, and Q4) merely shows a nexus of dietary consumption and Neu5Gcα 2,3 linked glycan sets:Neu5Gcα 2,6 linked glycan sets ratios. Although various other markers appears to be taught it is in combination with other markers not presently claimed. See Table 1. It must be concluded that Applicants’ claims of being
able to treat Neu5Gc related diseases and/or disorders are not enabled.
14. For reasons aforementioned, no claims are allowed.
15. 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 nonprovisional extension fee (37 CFR 1.17(a)) 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 mailing date of this final action.
16. Any inquiry concerning this communication or earlier communications from the examiner should be directed to LISA V COOK whose telephone number is (571)272-0816. The examiner works a flexible schedule but can normally be reached on Monday-Friday from 9am to 5pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Samira Jean-Louis, can be reached at telephone number 571-270-3503. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Lisa V. Cook
Patent Examiner
Art Unit 1642
Remsen
571-272-0816
3/21/26
/LISA V COOK/Primary Examiner, Art Unit 1642