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 .
Election/Restrictions
1. Applicant’s election with traverse of Group II (claims 66, 67, 69, 70, 73, 77, 78, and 79) in the reply filed on 6/24/26 is acknowledged. Applicant traverses the Restriction Requirement contending that Groups I, II and III have unity of invention because the groups share the same or corresponding technical features. More specifically, Applicant submits the special technical feature of the amended claims is measuring a biomarker in brain tumors, wherein the one or more brain tumor biomarkers is CTTNB1, DKK1, WIF1, TNC, GAD1, DDK2, EMX2, ATOH1, EYA1, HHIP, PDLIM3, SFRP1, NPR3, IMPG2, GABRA5, EGFL11, MAB21L2, KCNA1, EOMES, KHDRBS2, RBM24, UNC5D, or OAS1. This argument was carefully considered but was not found persuasive because the special technical feature does not make a contribution over the prior art.
For example, the reference to Mirzaei et al. (OncoImmunology, 2018, 7(10), e14786417/1-e1478647/14) discloses procedures for measuring TNC in brain tumors like glioblastoma. See reference, abstract, and pages 5-7; wherein the researchers present evidence that stem-like brain tumor-initiating cells (BTICs) produce the extracellular matrix protein tenascin-C (TNC) to inhibit T cell activity in live co-culture. In human glioblastoma brain specimens, TNC was widely deposited in the vicinity of T cells. Mechanistically, TNC inhibited T cell proliferation through interaction with α5β1 and αvβ6 integrins on T lymphocytes associated with reduced mTOR signaling.
TNC was exported out of BTICs associated with exosomes. And circulating exosomes from glioblastoma patients contained more TNC and T cell-suppressive activity than those from control individuals.
Additionally, this argument was not found persuasive because the Restriction Requirements dated 11/19/25 and 5/19/26 established Lack of Unity of Groups I, II, and III. The inventions require divergent search and consideration of the prior art and applicable rejections under 35 USC 112, 101, 102 and 103. Therefore, there is a burden to search all the inventions together.
2. Applicant has requested reconsideration of the claim grouping because independent claim 66 has been amended to recite "wherein the human is determined to have the brain tumor by a method comprising: assaying the level of one or more brain tumor biomarkers chosen from CTTNB1, DKK1, WIF1, TNC, GAD1, DDK2, EMX2, ATOH1, EYA1, HHIP, PDLIM3, SFRP1, NPR3, IMPG2, GABRA5, EGFL11, MAB21L2, KCNA1, EOMES, KHDRBS2, RBM24, UNC5D, and OAS1, in an exosomal sample obtained from the human; and comparing the level of the one or more brain tumor biomarkers in the exosomal sample from the human to the levels of the corresponding one or more brain tumor biomarkers in a reference exosomal sample, wherein an increase in the level of the one or more brain tumor biomarkers in the exosomal sample from the human compared to the reference exosomal sample indicates the presence of a sub-type of a brain tumor in the human" and now shares this special technical feature with independent claims 1, 36, and 105.
After reconsideration, claim 1 has been added to Group II for consideration. All other claims lack unity of invention as previously indicated.
3. The requirement is still deemed proper and is therefore made FINAL.
4. Claims 36, 80, 83, 85, 91, 92, 94, 95, 98, 101, 102, 103, 104, and 105 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 with traverse in the reply filed on 6/24/26. Currently claims 1, 66, 67, 69, 70, 73, 77, 78, and 79 are under consideration.
Priority
5. The instant application has a priority date of April 22, 2020. This application is a 371 of PCT/US21/28431 filed 4/21/21 and provisional application PRO 63/013,800 filed 4/22/20.
Information Disclosure Statement
6. The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609 A(1) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the Examiner on form PTO-892 or Applicant on PTO-1449 cited the references they have not been considered.
7. The information disclosure statement filed 5/24/24 has been considered as to the merits before First Action.
Specification
8. The use of the term “TWEEN”, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore, the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term. For example, see page 25 line 1
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
9. This application makes reference to or appears to claim subject matter disclosed in 371 of PCT/US21/28431 filed 4/21/21 and provisional application PRO 63/013,800 filed 4/22/20. If applicant desires to claim the benefit of a prior-filed application under 35 U.S.C. 119(e), 120, 121, 365(c) or 386(c), the instant application must contain, or be amended to contain, a specific reference to the prior-filed application in compliance with 37 CFR 1.78. The specific reference must be included in the first sentence(s) of the specification following the title. Pease add to the disclosure.
Abstract
10. This application does not contain an abstract of the disclosure as required by 37 CFR 1.72(b). An abstract on a separate sheet is required.
Claim Objections
11. Claims 1, 66, 70, 77, and 78 are objected to because of the following informalities: The claim utilizes several acronyms “CTTNB1, DKK1, WIFI, TNC, GAD1, EMX2, DMA, etc.” without first defining what they represent in the independent claim. While the claims can reference acronyms, the material presented by the acronym must be clearly set forth at the first use of the acronym. Although the term may have art recognized meaning, it is necessary to define the acronym to clearly set forth Applicant’s intent. For example, CTTNB1 is (Catenin Beta 1) as defined on page 7 lines 14-33 of the specification. However, Applicant is cautioned not to introduce new matter into the claims. Appropriate correction is required
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.
12. Claims 1, 66, 67, 69, 70, 73, 77, 78, and 79 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 The term “sub-type” in claims 1 and 66 is a relative term which renders the
claim indefinite. The term “sub-type” 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. As recited the metes and bounds of the claim cannot be determined. It is suggested that the actual detected brain tumor is included in the claim to obviate the rejection. Appropriate correction is required.
B. Claim 1 is vague and indefinite because it is not clear if the anti-exosome therapeutic agent inhibitor of neutral sphingomyelinase and exosome biogenesis and an inhibitor of the secretion of exosomes. Or selected from one of inhibitor of neutral sphingomyelinase, an inhibitor of exosome biogenesis or an inhibitor of the secretion of exosomes. It appears that an article (and, or, selected from the group of) is omitted and makes the claim ambiguous. Appropriate correction 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.
13. Claims 1, 66, 67, 69, 70, 73, 77, 78, and 79 are rejected under 35 U.S.C. 101 because the claimed invention is not directed to a judicial exception or JE (i.e. natural phenomena-measuring biomarkers found in nature and abstract idea-comparison to a reference control) without significantly more.
The independent claim(s) recite(s):
Claim 1. A method of identifying a human having a brain tumor, the method comprising: assaying the level of one or more brain tumor biomarkers in an exosomal sample obtained from the human, wherein the one or more brain tumor biomarkers is CTTNB1, DKK1, WIF1, TNC, GAD1, DDK2, EMX2, ATOH1, EYA1, HHIP, PDLIM3, SFRP1, NPR3, IMPG2, GABRA5, EGFL11, MAB21L2, KCNA1, EOMES, KHDRBS2, RBM24, UNC5D, or OAS1; comparing the level of the one or more brain tumor biomarkers in the exosomal sample from the human to the levels of the corresponding one or more brain tumor biomarkers in a reference exosomal sample, wherein an increase in the level of the one or more brain tumor biomarkers in the exosomal sample from the human compared to the reference exosomal sample indicates the presence of a sub-type of a brain tumor in the human; and administering an anti-exosome therapeutic agent to the human.
Claim 66. A method of treating a human having a brain tumor comprising administering to the human having the brain tumor an anti-exosome therapeutic agent, wherein the human is determined to have the brain tumor by a method comprising: assaying the level of one or more brain tumor biomarkers chosen from CTTNB1, DKK1, WIF1, TNC, GAD1, DDK2, EMX2, ATOH1, EYA1, HHIP, PDLIM3. SFRP1, NPR3, IMPG2, GABRA5, EGFL11, MAB21L2, KCNA1, EOMES, KHDRBS2, RBM24, UNC5D, and OASI, in an exosomal sample obtained from the human; and comparing the level of the one or more brain tumor biomarkers in the exosomal sample from the human to the levels of the corresponding one or more brain tumor biomarkers in a reference exosomal sample, wherein an increase in the level of the one or more brain tumor biomarkers in the exosomal sample from the human compared to the reference exosomal sample indicates the presence of a sub-type of a brain tumor in the human.
The judicial exception (natural phenomena) is not integrated into a practical application because determining natural biomarkers (CTTNB1, DKK1, WIF1, TNC, GAD1, DDK2, EMX2, ATOH1, EYA1, HHIP, PDLIM3, SFRP1, NPR3, IMPG2, GABRA5, EGFL11, MAB21L2, KCNA1, EOMES, KHDRBS2, RBM24, UNC5D, or OAS1) in a biological sample, comparing data (reference control levels), and determining brain tumor by merely thinking about the results does not practically apply the judicial exception. Although the methods recite a treatment or administering an anti-exosome therapy, the treatment is not necessarily performed.
In other words, there is no corresponding action with respect to the knowledge provided by the judicial exception.
The method of claims 1 and 66 read on administering an anti-exosome therapy when the “marker level is increased” to thereby demonstrate a change in comparison to a reference.
However, the claims includes a conditional limitation because the treatment is not conducted if the increased biomarker level is not observed; therefore, the method reads on instances where the treatment does not occur (protein levels equal to or decreased in comparison to the reference level).
Accordingly, the claims do not integrate the JE into a practical application. Examiner directs Applicant to the case law (Vanda Pharmaceuticals Inc. v. West-Ward Pharmaceuticals, 887 F. 3d 1117) and PTO guidance emphasizing that method of treatment claims can be found to satisfy 35 USC § 101 at the first step of an Alice/Mayo analysis, without requiring a showing of “non-routine or unconventional steps”.
Unlike Vanda’s claims, where administering is required for all populations of patients, in instant case, the broadest reasonable interpretation of the claimed scope is that the treatment steps or therapy are not necessarily performed. The steps of “comparing” in claims 1 and 66 do not actually require an active wet step 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.).
The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the assaying, comparing, and administering steps do not transform the method into an inventive process. The additional steps do not amount to significantly more than the judicial exception.
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 (natural phenomena). The rationale for this determination is explained below:
A claim that focuses on use of a natural principle (method merely identifying or determining the natural compositions of CTTNB1, DKK1, WIF1, TNC, GAD1, DDK2, EMX2, ATOH1, EYA1, HHIP, PDLIM3, SFRP1, NPR3, IMPG2, GABRA5, EGFL11, MAB21L2, KCNA1, EOMES, KHDRBS2, RBM24, UNC5D, or OAS1) 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.
Specifically, 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.
Claims 1, 66, 67, 69, 70, 73, 77, 78, and 79 as currently recited encompass measurements in individuals with or without having a brain tumor, who will not necessarily receive an exosome therapeutic treatment. 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 natural composition of CTTNB1, DKK1, WIF1, TNC, GAD1, DDK2, EMX2, ATOH1, EYA1, HHIP, PDLIM3, SFRP1, NPR3, IMPG2, GABRA5, EGFL11, MAB21L2, KCNA1, EOMES, KHDRBS2, RBM24, UNC5D, or OAS1; naturally found in an individual; and measuring differential expression in brain tumors. See claims 1, 66, 67, 69, 70, 73, 77, 78, and 79.
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 “assaying, comparing, and administering an anti-exosome therapy” are 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 said biomarker levels; and also because the “assay, comparing to a reference control, and administering” steps do not relate to the natural principle in a significant way to impose a meaningful limit on the claim scope.
Limitations that are necessary for all practical applications of the natural principle, such that everyone practicing the natural principle would be required to perform those steps or every product embodying that natural principle would be required to include those features, would not be sufficient to confer patent eligibility.
In addition, appending conventional steps, specified at a high level of generality, to a natural principle does not make the claim patent-eligible.
Steps that amount to instructions that are well-understood, routine, conventional activity, previously engaged in by those in the field add nothing specific to the natural principle that would render it patent-eligible.
In this case, it was known to measure one or more biomarkers from CTTNB1, DKK1, WIF1, TNC, GAD1, DDK2, EMX2, ATOH1, EYA1, HHIP, PDLIM3, SFRP1, NPR3, IMPG2, GABRA5, EGFL11, MAB21L2, KCNA1, EOMES, KHDRBS2, RBM24, UNC5D, or OAS1 in brain tumor patients. See for example the reference to Mirzaei et al. (OncoImmunology, 2018, 7(10) e1478647/1-14).
The instantly claimed invention when given its broadest reasonable interpretation (BRI) reads on a method (claims 1 and 66) measuring one or more biomarkers from CTTNB1, DKK1, WIF1, TNC, GAD1, DDK2, EMX2, ATOH1, EYA1, HHIP, PDLIM3, SFRP1, NPR3, IMPG2, GABRA5, EGFL11, MAB21L2, KCNA1, EOMES, KHDRBS2, RBM24, UNC5D, or OAS1 with or without additional biomarkers (comprising) in a test sample wherein the detection may or may not be indicative of a brain tumor. The step of assaying or determining is therefore insufficient to render the claim patent eligible, since it represents well-understood, routine, and conventional activity that was previously engaged in by those in the field.
Furthermore, the additional elements set forth in the dependent claims also represent well-understood, routine, conventional activity that was previously engaged in by those in the field.
In other words, CTTNB1, DKK1, WIF1, TNC, GAD1, DDK2, EMX2, ATOH1, EYA1, HHIP, PDLIM3, SFRP1, NPR3, IMPG2, GABRA5, EGFL11, MAB21L2, KCNA1, EOMES, KHDRBS2, RBM24, UNC5D, or OAS1 with additional biomarkers are naturally occurring products and the claimed methods identifying them merely amount to routine activity that is not patent eligible.
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 naturally occurring CTTNB1, DKK1, WIF1, TNC, GAD1, DDK2, EMX2, ATOH1, EYA1, HHIP, PDLIM3, SFRP1, NPR3, IMPG2, GABRA5, EGFL11, MAB21L2, KCNA1, EOMES, KHDRBS2, RBM24, UNC5D, or OAS1 with additional biomarkers levels in patients would require additional steps that do significantly more to apply this principle than conventional marker 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.
Additionally Claim(s) 1, 66, 67, 69, 70, 73, 77, 78, and 79 are also directed to abstract ideas as independent claims 1 and 66 recite “comparing the detected marks to a reference control” (reading on mental processes). Comparing information regarding a sample or test subject to a control or target data 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. See July 2015 Update, Quick Reference Guide.
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 (CTTNB1, DKK1, WIF1, TNC, GAD1, DDK2, EMX2, ATOH1, EYA1, HHIP, PDLIM3, SFRP1, NPR3, IMPG2, GABRA5, EGFL11, MAB21L2, KCNA1, EOMES, KHDRBS2, RBM24, UNC5D, or OAS1 biomarkers) merely narrows the abstract idea, which does not make the comparison step less abstract and is not sufficient to provide eligibility on its own.
101 Analysis – Claims 1 and 66
Step 1: – Is the claim to a process, machine, manufacture or composition of matter?
YES. The claims recite a step or act, i.e. method of identifying and/or determining a brain tumor for treatment by measuring CTTNB1, DKK1, WIF1, TNC, GAD1, DDK2, EMX2, ATOH1, EYA1, HHIP, PDLIM3, SFRP1, NPR3, IMPG2, GABRA5, EGFL11, MAB21L2, KCNA1, EOMES, KHDRBS2, RBM24, UNC5D, or OAS1 and administer an anti-exosome therapy. Thus, the claim is directed to a process.
Step 2A Prong 1: Is the claim directed to a law of nature, a natural phenomenon, or an abstract idea?
Yes. The claim recites a step of assaying, comparing, and administering treatment based on CTTNB1, DKK1, WIF1, TNC, GAD1, DDK2, EMX2, ATOH1, EYA1, HHIP, PDLIM3, SFRP1, NPR3, IMPG2, GABRA5, EGFL11, MAB21L2, KCNA1, EOMES, KHDRBS2, RBM24, UNC5D, or OAS1 biomarkers levels. This reads on comparing or mental activities that are abstract ideas (JE). The steps of comparing (determining presence or level) is recited a high level of generality that merely requires a comparison of two pieces of information and imposes no limits on how the comparison is performed. In Myriad CAFC, the court round this step of comparing to be an abstract idea. When applying the 2014 IEG and interpreting the claim during examination, it is apparent that the step of comparing (determining presence or level) could be performed by a human using mental steps or basic critical thinking.
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 (CTTNB1, DKK1, WIF1, TNC, GAD1, DDK2, EMX2, ATOH1, EYA1, HHIP, PDLIM3, SFRP1, NPR3, IMPG2, GABRA5, EGFL11, MAB21L2, KCNA1, EOMES, KHDRBS2, RBM24, UNC5D, or OAS1) merely narrows the abstract idea, which does not make the comparison step less abstract and is not sufficient to provide eligibility on its own.
Thus, the claim is directed to an abstract idea. The claim is drawn to an abstract ideas in what they are directed to a method for collecting and comparing information regarding a sample or test subject to a control or target data (Ambry/Myriad CAFC).
Step 2A Prong 2: Is the JE integrated into a practical application?
No, there is not action on the JE. The method merely requires thinking about the information or results obtained (comparison and possibly administering a treatment) reading on instances wherein the JE is not physically acted on.
Step 2B: Does the claim as a whole amount to significantly more than the judicial exception, i.e. the product of nature, law of nature, natural phenomenon, or abstract idea? Inventive concept
The claim as a whole is analyzed to determine whether any additional element, or combination of elements, is sufficient to ensure that the claim amounts to significantly more than the abstract idea. The claim recites steps of assaying CTTNB1, DKK1, WIF1, TNC, GAD1, DDK2, EMX2, ATOH1, EYA1, HHIP, PDLIM3, SFRP1, NPR3, IMPG2, GABRA5, EGFL11, MAB21L2, KCNA1, EOMES, KHDRBS2, RBM24, UNC5D, or OAS1 biomarkers are all well understood, routine and conventional procedures. Accordingly, the claims as a whole do not amount to significantly more than the abstract idea of comparing/determining information (evaluating data). The claim is not patent eligible.
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception. The method of claims 1, 66, 67, 69, 70, 73, 77, 78, and 79 are generally directed to collecting information and comparing the data to determine/treat brain tumor. The use of conventional, well understood, and routine activities previously known to the industry, specified at a high level of generality, had been held NOT to be enough to qualify as “significantly more” when recited in a claim with a judicial exception.
Determining whether CTTNB1, DKK1, WIF1, TNC, GAD1, DDK2, EMX2, ATOH1, EYA1, HHIP, PDLIM3, SFRP1, NPR3, IMPG2, GABRA5, EGFL11, MAB21L2, KCNA1, EOMES, KHDRBS2, RBM24, UNC5D, or OAS1 biomarkers are present in a sample merely instructs a scientist to use any detection technique. When recited at this high level of generality, there is no meaningful limitation, such as a particular or unconventional machine or transformation of a particular article, in this step that distinguishes it from well-understood, routine and conventional data gathering activity engaged in by scientist prior to applicant’s invention, and at the time the application was filed. Further, it is well established that the mere physical or tangible nature of additional elements such as the obtaining and detecting steps does not automatically confer eligibility on a claim directed to an abstract idea (see, e.g., Alice Corp. v. CLS Bank Int’l, 134 S.Ct. 2347, 2358-59 (2014)).
For all of the reasons above, at least claims 1, 66, 67, 69, 70, 73, 77, 78, and 79 fail to include additional elements that are sufficient to amount to significantly more than the judicial exception(s).
Claims 1, 66, 67, 69, 70, 73, 77, 78, and 79 are directed to the additional step of measuring by known routine assay techniques. As such, claims 1, 66, 67, 69, 70, 73, 77, 78, and 79 fail to include additional elements that are sufficient to amount to significantly more than the judicial exception.
Claim Rejections - 35 USC § 103
14. 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.
15. Claim(s) 1, 66, 67, and 69 is/are rejected under 35 U.S.C. 103 as being unpatentable over Mirzaei et al. (OncoImmunology, 2018, 7(10), e14786417/1-e1478647/14) in view of Lyden et al. (WO 20102/135844).
Mirzaei et al. (OncoImmunology, 2018, 7(10), e14786417/1-e1478647/14) discloses procedures for measuring TNC in brain tumors like glioblastoma.
See reference, abstract, and pages 5-7; wherein the researchers present evidence that stem-like brain tumor-initiating cells (BTICs) produce the extracellular matrix protein tenascin-C (TNC) to inhibit T cell activity in live co-culture. In human glioblastoma brain specimens, TNC was widely deposited in the vicinity of T cells. Mechanistically, TNC inhibited T cell proliferation through interaction with α5β1 and αvβ6 integrins on T lymphocytes associated with reduced mTOR signaling.
TNC was exported out of BTICs associated with exosomes. And circulating exosomes from glioblastoma patients contained more TNC and T cell-suppressive activity than those from control individuals.
The measurement of TNC increased levels is deemed a “sub-type” of brain tumor because elevated TNC was found in a select group of exosomes from BTICs.
Mirzaei et al. differ from the instant invention in not specifically treating the brain tumor patient with an anti-exosome therapeutic agent.
However, Lyden et al. disclose a method of identifying (a method of diagnosing and treating metastatic disease type in a subject; paragraph [0013]) a human (the subject or patient is a human; paragraph [0039]) having a brain tumor (treating metastatic disease including metastatic brain cancer in a subject, exosome treated animals developed metastatic disease in brain, protein per milliliter plasma in exosomes in glioblastoma multiforme cancer patients were compared to that in healthy donors, where glioblastoma is the brain tumor; (abstract; paragraphs [0031], [0037], [0124]), the method comprising: assaying the level of one or more brain tumor biomarkers in an exosomal sample (obtaining an exosomal sample from the subject and detecting one or more biomarkers of metastatic disease type in the sample; paragraph [0013]) obtained from the human (the subject or patient is a human; paragraph [0039]); comparing the level of the one or more brain tumor biomarkers in the exosomal sample (obtaining an exosomal sample from the subject and detecting one or more biomarkers of metastatic disease type in the sample; paragraph [0013]) from the human (the subject or patient is a human; paragraph [0039]) to the levels of the corresponding one or more brain tumor biomarkers (in exosomal sample, detecting one or more biomarkers of metastatic disease type in the sample; paragraph [0013] in a reference exosomal sample (protein per milliliter plasma in exosomes in glioblastoma multiforme cancer patients were compared to that in healthy donors, i.e., the reference, exosomal expression level from the subject's sample is compared to reference exosomal expression levels of the corresponding proteins, i.e., the markers, increase in exosomal expression of the measured proteins indicates the subject is at risk for developing metastatic disease; paragraphs [0031], [0040], wherein an increase in the level of the one or more brain tumor biomarkers in the exosomal sample from the human compared to the reference exosomal sample indicates the presence of a sub-type (exosomal expression level from the subject's sample is compared to reference exosomal expression levels of the corresponding proteins, i.e., the markers, increase in exosomal expression of the measured proteins indicates the subject is at risk for developing metastatic disease; paragraph [0040]) of a brain tumor (exosome treated animals developed metastatic disease in brain, protein per milliliter plasma in exosomes in glioblastoma multiforme cancer patients were compared to that in healthy donors, where glioblastoma is the brain tumor, abstract; paragraphs [0031], [0037], [0124]) in the human the subject or patient is a human; paragraph [0039]);
and administering an anti-exosome (method of administering to the subject an agent that inhibits primary tumor cell exosomes to inhibit primary tumor growth and treating the identified metastatic disease type, delivery vehicle to deliver nucleic acid molecules encode an anti-exosome antibody; paragraphs [0009], [0013], [0072]) therapeutic agent (identifying the metastatic disease type based on detecting and administering a therapeutic agent to the subject that is suitable for treating the identified metastatic disease type; paragraph [0013]) to the human (the subject or patient is a human; paragraph [0039]).
As per claim 66, Lyden discloses a method of treating (a method of diagnosing and treating metastatic disease type in a subject; paragraph [0013]) a human (the subject or patient is a human; paragraph [0039]) having a brain tumor (treating metastatic disease including metastatic brain cancer in a subject, exosome treated animals developed metastatic disease in brain, protein per milliliter plasma in exosomes in glioblastoma multiforme cancer patients were compared to that in healthy donors, where glioblastoma is the brain tumor, abstract; paragraphs [0031], [0037], [0124]) comprising administering to the human in need thereof an anti-exosome therapeutic agent (method of identifying the metastatic disease type in the subject and administering to the subject an agent that inhibits primary tumor cell exosomes to inhibit primary tumor growth and treating the identified metastatic disease type, delivery vehicle to deliver nucleic acid molecules encode an anti-exosome antibody; paragraphs [0009], [0013], [0072]).
As per claim 67, Lyden discloses the method according to claim 66, and Lyden further discloses wherein the brain tumor is a glioblastoma (treating metastatic brain cancer in a subject, protein per milliliter plasma in exosomes in glioblastoma multiforme cancer patients were compared to that in healthy donors; paragraphs [0031], [0037], [0135]).
As per claim 69/66, Lyden discloses the method according to claim 66, and further discloses the anti-exosome therapeutic agent (method of administering to the subject an agent that inhibits primary tumor cell exosomes under conditions effective to inhibit primary tumor growth, delivery vehicle to deliver nucleic acid molecules encoding an anti-exosome antibody; paragraphs [0009], [0072]).
It would have been prima facie obvious to one of ordinary skill before the effective filing date of the instant invention to treat the patients identified to have TNC elevated BTICs as exemplified by Mirzaei et al. with the anti-exosomal therapeutic agent taught by Lyden et al. because Lyden et al. their method was useful in identifying candidate compounds for treating and preventing metastatic diseases and tumor growth. See abstract.
One skill in the art would have been motivated to treat the patient with an anti-exosomal therapeutic in order to provide efficacy and disease eradication.
16. Claims 70, 73, 77, 78, and 79 is/are rejected under 35 U.S.C. 103 as being unpatentable over Mirzaei et al. (OncoImmunology, 2018, 7(10), e14786417/1-e1478647/14) in view of Lyden et al. (WO 20102/135844) and further in view of (Dai, X et al.) “AHIF promotes glioblastoma progression and radioresistance via exosomes.” (International Journal of Oncology January 2019, Epub 2 November 2018, Vol. 54, No 1; pages 261-270), DOI: 10.3892/jo.2018.4621.
Please see Mirzaei et al. (OncoImmunology, 2018, 7(10), e14786417/1-e1478647/14) in view of Lyden et al. (WO 20102/135844) as set forth above.
Mirzaei et al. (OncoImmunology, 2018, 7(10), e14786417/1-e1478647/14) in view of Lyden et al. (WO 20102/135844) differ from the instant invention in not teaching the utility of an anti-exosome therapeutic agent is an inhibitor of neutral sphingomyelinase and exosome biogenesis.
Dai et al. discloses wherein the anti-exosome therapeutic agent is an inhibitor of neutral sphingomyelinase and exosome biogenesis (glioblastoma multiforme GBM cells with upregulated hypoxia inducible factor 1 alpha AHIF), were treated with exosomal inhibitor GW4869, which decreased invasive and anti-apoptosis abilities of GBM, where GW4869 is the anti-exosome therapeutic agent is an inhibitor of neutral sphingomyelinase and exosome biogenesis; abstract; page 263, second column, second paragraph; page 267, second column, second paragraph; page 268, first column, first paragraph).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the invention, to have modified the method of Mirzaei et al. in view of Lyden, to provide for anti-exosome therapeutic agent that is an inhibitor of neutral sphingomyelinase and exosome biogenesis, because as previously disclosed by Dai et al. said treatments were suitable for brain tumor (Dai; abstract; page 263, second column, second paragraph; page 267, second column, second paragraph; page 268, first column, first paragraph), for providing an example of the anti-exosome therapeutic agent (Dai; paragraphs [0009], [0072]) that would be suitable for the treatment of brain tumor (Dai; paragraphs [0031], [0037], [0135]).
With respect to the known treatment combinations recited in claims 78 and 79, it is noted that routine optimization of treatment compounds is an obvious modification of the methods previously taught by the prior art. Absent evidence to the contrary the modification of treatment is deemed an obvious design choice previously taught by the prior art.
The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945); In re Leshin, 277 F.2d 197, 125 USPQ 416 (CCPA 1960); Ryco, Inc. v. Ag-Bag Corp., 857 F.2d 1418, 8 USPQ2d 1323 (Fed. Cir. 1988).
Therefore it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to include the brain tumor treatment compounds and/or procedures previously employed to treat said tumors as a routine design choice to provide better specificity and sensitivity to the brain tumor treatment.
17. For reasons aforementioned, no claims are allowed.
18. Any inquiry concerning this communication or earlier communications from the Examiner should be directed to LISA COOK whose telephone number is (571)272-0816. The Examiner works a flexible schedule, however she can generally be reached 9AM-5PM, Monday, Thursday, and Friday.
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Lisa Cook
Patent Examiner
Art Unit 1641
9/5/26
/LISA V COOK/Primary Examiner, Art Unit 1641
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