DETAILED ACTION
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
Applicant’s election without traverse of the species comprising target region 468-488 and the ASO shown in SEQ ID NO: 240 in the reply filed on March 24, 2026, is acknowledged. Claims 4-7 and 10-11 withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on March 24, 2026.
The elected ASO, SEQ ID NO 240, appears to be free of the art. During the course of searching an ASO having the sequence CACACACACACACACACACAC was identified. The species election was widened to include an ASO with this sequence.
Status of Claims
Claims 1-3, 8-9, 12-24 are under consideration.
Specification
The specification on pg. 13 describes four ASOs – ASO1, ASO2, ASO3, and ASO4 that are designed and tested. These are described as having PN linkages and LNA. However, everywhere else in the document, the linkages are described as PS linkages. Further, the abbreviation, PN, is not one known in the art nor is it defined in the disclosure. Clarification is requested.
The use of the term Alexa647, has been noted in the specification, pg. 10, line 4. The correct name is "Alexa FluorTM 647" which is a trade name or a mark used in commerce, has been noted in this application.
The use of the term IVIS, has been noted in the specification, pg. 10, line 2, at least.
Similarly, Applicant is requested to check the specification for other instances of probably trade names or marks used in commerce.
The terms 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.
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.
Claim Objections
Claim 1 is objected to because of the following informalities: there is a grammar issue in claim 1 reciting “comprising an antisense oligonucleotides” rather than “comprising an antisense oligonucleotide…” or “comprising antisense oligonucleotides…”.
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.
Claims 3, 12-13, and 18-24 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 3 and 18, the claims recite the parenthetical expression “(SEQ ID NO: 200)”. The metes and bounds of claims 3 and 18 are rendered vague and indefinite by using the parenthetical with the SEQ ID NO. Such parenthetical recitations are indefinite because it is unclear as to whether the limitations are part of the instantly claimed subject matter. For e.g., it is not clear if the ASOs have to target SEQ ID NO: 200 or just any lnc-HLX-2-7 sequence – including sequences in the human population that may have SNPs. The specification does not discuss SNPs but Yang (Yang et al., Nucleic Acids Research, 2023, Vol. 51, Database issue, Published online 9 November 2022) discuss SNPs are present in lncRNAs and that the field is continually evolving (abstract).
Regarding claim 12, claim 12 recites "The method of claim 19, wherein the composition further comprises a polymeric micelle.”. Claim 19 recites "The composition of claim 18, wherein…” and claim 18 recites "A composition comprising an ASO that targets a 20-40 nucleotide sequence of Inc-HLX-2-7 (SEQ ID NO:200).”.
However, claim 12 is directed to the “operation”, per se, of a composition rather than its “structure” and, therefore, is confusing. First, it is unclear whether the above limitation is intended to be directed to a series of steps for the “making” of the composition include a polymeric micelle to which no steps are recited or to be directed to a series of steps for the “use” of the composition within a polymeric micelle to which, again, no steps are recited. A claim which claims both an apparatus and the method steps of using the apparatus would be considered indefinite. See M.P.E.P. 2173.05(p). Accordingly, clarification and appropriate correction for the above limitation recited in the claims is requested.
In the interest of compact prosecution, claim 12 will be interpreted as a method.
Regarding claims 19 and 21, claim 19 recites The composition of claim 18, wherein the 20-40 nucleotide sequence comprises nucleotides 110-132,… or nucleotides 494-516, and claim 21 recites The composition of claim 18, wherein the 20-40 nucleotide sequence comprises nucleotides 325-345, nucleotides 335-361, nucleotides 468-488 or nucleotides 480- 500. This does not make sense. The range of nucleotides provided must correspond to a sequence identified by a SEQ ID NO. In the absence of the latter, what the recited nucleotides correspond to could be an infinite number of things. Therefore, the claims are indefinite.
Those claims identified in the statement of rejection but not explicitly referenced in the rejection are also rejected for depending from a rejected claim but failing to remedy the indefiniteness therein.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 12 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
MPEP 608.01(n) Dependent Claims [R-01.2024] further states:
In accordance with 35 U.S.C. 112(d), or pre-AIA 35 U.S.C. 112, fourth paragraph, a claim in dependent form shall contain:
(i) a reference to a claim previously set forth, and
(ii) then specify a further limitation of the subject matter claimed.
In the instant case, claim 12 depends upon claim 19, which is NOT previously set forth, rather follows claim 12 in the claim listing.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Scope of Enablement
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.
Claim 14 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for detecting overexpression of lnc-HLX-2-7 in a biopsy obtained from a patient having group III medulloblastoma, does not reasonably provide enablement for the method of detecting overexpression of lnc-HLX-2-7 using any sample in any medulloblastoma. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
Regarding claim 14, claim 14 recites sample wherein the sample is not defined in the specification. The specification in pg. 16, 2nd para states “In specific embodiments, the biological sample is a tissue sample”. However, this is not a limiting definition. Further, the art does not indicate that a blood sample, which is encompassed within the term “sample” may be diagnostic in medulloblastoma. However, from the knowledge in the field, it appears as if the sample is only limited to a lumbar puncture (spinal tap) as discussed below:
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue.” See MPEP § 2164. These factors include, but are not limited to: The breadth of the claims; The nature of the invention; The state of the prior art; The level of one of ordinary skill; The level of predictability in the art; The amount of direction provided by the inventor; The existence of working examples; The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
With respect to the breadth of the claims, the claims as currently drafted are directed to the detection of lnc-HLX-2-7 from any biological sample that is known to contain lnc-HLX-2-7. Consequently, the breadth of this limitation of the claim is broad.
The invention is in the field of diagnostics and treatment of a Group III medulloblastoma. Regarding the nature of the invention, the claimed invention is detection of lnc-HLX-2-7, which may be diagnostic of Group III medulloblastoma. The invention further comprises a method of treating Group III medulloblastoma by inhibiting expression of lnc-HLX-2-7 with an ASO. Due to the nature of the invention relying on 1. the detection of lnc-HLX-2-7 and 2. any means of administration of ASO, it will be necessary that the sample is clear of any endogenous levels or any detected levels may not be mistaken for levels of lnc-HLX-2-7 that do not reflect Group III medulloblastoma. This is the method foreseen by one of ordinary skill in the art. Yet, the claims do not limit the sample to a particular specimen and the specification does not shed any light on what may be a diagnostic sample and what may not. Therefore to make such a claimed method perform as described, i.e., detect lnc-HLX-2-7 in any biological sample, will be undue burden as it will require undue experimentation.
With respect to the state of the prior art, MRI, CT, and a lumbar puncture (spinal tap) assays are used routinely for diagnostic purposes, Medulloblastoma Resource, retrieved from theMedulloblastoma.org webpage on the internet <Diagnosing Medulloblastoma – MRI, Lumbar Puncture & Staging> 4 pages [retrieved on 21st April 2026].. Information from the first page on the Mayo Clinic, retrieved from the Mayo Clinic webpage on the internet <Medulloblastoma - Diagnosis and treatment - Mayo Clinic> 13 pages [retrieved on 21st April 2026] states: Tissue samples may also be tested. A tissue sample is usually taken during surgery to remove the tumor. This procedure is called a brain biopsy. A biopsy is a procedure to remove a sample of tissue for testing in a lab. The sample is tested in a lab to confirm that it is medulloblastoma. A separate biopsy alone is uncommon and is used only in certain situations.
d. With respect to level of skill in the art, an artisan of ordinary skill in the art recognizes that not all samples may be used that contain or potentially contain detectable levels of lnc-HLX-2-7, which in turn correlate with medulloblastoma. A skilled artisan recognizes that certainly a breath sample, nail clippings, even blood, etc., all of which are encompassed by the term sample, will not function as required by the claims.
With respect to the predictability of the art, in view of the state of the art and the level of skill in the art, interchangeable use of various samples is unpredictable.
The applicants have not provided sufficient direction to practice the full scope of the claimed invention. The applicants have not provided working examples that shows that other than tissue sections or in vitro assays, any sample could be used interchangeably in their claimed method.
The applicants have not provided any working example directed to use of any sample in lieu of tissue sections. The specification on page 21, Materials and Methods section, discloses obtaining tissue samples of Group III medulloblastoma and obtaining RNA from them; The specification on page 23, describes Immunohistochemistry was performed on tumor sections; The specification on page 24, describes cr4eating a library from RNA prepared from cell lines and orthotopic xenografts; The specification on end of page 24, describes FISH assay performed on paraffin-embedded tissue sections. Thus, in all these examples, a tissue was used to detect the lnc-HLX-2-7 or to determine effects of treatment after treating with ASO to lnc-HLX-2-7.
As is evident from the prior art and the instant disclosure, undue experimentation would be required to practice the invention as claimed due to the amount of experimentation necessary because of the specific nature of the claims, the state of the prior art and its unpredictability, the high level of skill required to practice the alleged invention and the limited amount of guidance in the form of varied working examples in the specification.
MPEP §2164.01(a), 4th paragraph, provides that, “A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1157, 1562; 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).
Genentech Inc. v. Novo Nordisk A/S, 42 USPQ2d 1001, 1005 (CA FC), states that, “[p]atent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable,” citing Brenner v. Manson, 383 U.S. 519, 536 (1966) (stating, in the context of the utility requirement, that “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion”). The Genentech decision continued, “tossing out the mere germ of an idea does not constitute enabling disclosure. While every aspect of a generic claim certainly need not have been carried out by an inventor, or exemplified in the specification, reasonable detail must be provided in order to enable members of the public to understand and carry out the invention.” Id. at p. 1005.
After applying the Wands factors and analysis to claim 14, in view of the applicant’s entire disclosure, and considering the In re Wright and Genentech decisions discussed above, it is concluded that the practice of the invention as claimed in claims 1 would not be enabled by the written disclosure for any sample. Therefore, claim 14 is rejected under 35 U.S.C. §112(a) for failing to disclose sufficient information to enable a person of skill in the art to make and use the claimed invention in its full scope.
Claims 1-3, 8-9, and 12-24 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method for treating Group III medulloblastoma in a patient comprising the step of administering a composition comprising a modified antisense oligonucleotides (ASO) with a delivery agent targeting long non- coding ribonucleic acid HLX-2-7 (lnc-HLX-2-7), does not reasonably provide enablement for the method using unmodified ASO treating any medulloblastoma targeting any region of lnc-HLX-2-7. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
To be enabling, the Specification must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1561 (Fed. Cir. 1993). The determination that "undue experimentation" would have been needed to practice the claimed invention in full scope is not a single, simple factual determination.
As stated in the MPEP 2164.01(a), “There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is "undue." In In re Wands, 8 USPQ2d 1400 (1988), factors to be considered in determining whether a disclosure meets the enablement requirement of 35 U.S.C. 112, first paragraph, have need described. They are:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. Keeping that in mind, the Wands factors are relevant to the instant application for the following reasons:
The breadth of the claim
The instant claims are broad and are directed to an antisense oligonucleotide composition for administration to a subject in need thereof comprising a therapeutic agent consisting of a non-conjugated, with or without chemical modifications, antisense oligonucleotide. Further, the claims are broad because they include a therapeutic oligonucleotide targeting any region of the target gene and “administering a composition” includes:
All subject types and all medulloblastoma types
All routes of administration
All delivery agents
The nature of the invention
The claims are drawn to hard-to-treat Grade III medulloblastoma treatment methods by administering antisense oligonucleotide agents and therapeutics to a living human beings/subjects/patient, and therefore, the invention is in a class of invention which the CAFC has characterized as “the unpredictable arts such as chemistry and biology.” Mycogen Plant Sci., Inc. v. Monsanto Co., 243 F.3d 1316, 1330 (Fed. Cir. 2001).
The level of predictability in the art
The state of the art at the time the invention was filed was unpredictable.
The review article of Desgraves (Desgraves et al., Cancers 2024, 16(10), 1944) discusses that ASOs have the potential to be used in the treatment of brain disorders as significant improvements in design have been made though “clinical trials are warranted to validate ASOs as a transformative approach in neuro-oncology” (abstract). First-generation ASOs were unmodified and so i) showed decreased efficiency in vivo and high rates of decay, primarily due to the activity of the abundant exo- and endonucleases found in bodily fluids and within the cell and ii) also poorly tolerated due to their immunostimulatory properties. Second-gen ASO incorporate a combination of : phosphorothioate (PS) backbones, in which one of the non-bridging oxygens of the phosphate group is replaced with sulfur, substantially decrease the nuclease activity and enhance the target affinity; and conjugates added to the 2′ hydroxyl (-OH) group of the ribose ring such as a methyl or methoxyethyl group, to result in decreased off-target effects and drug-related side effects (section 2. Chemical Modifications). Pertinent to instant application is crossing the blood–brain barrier (BBB). Desgraves state BBB is a significant obstacle for therapeutic options aimed at malignancies within the CNS, including ASOs (3. Delivery Methods). Nanoparticles have been shown in several studies to penetrate the BBB and enhance delivery of ASO. After central administration (intrathecal or intraventricular) of an ASO to rodents, researchers observed a widespread distribution throughout the CNS (same section, last para). Further, single modifications alone are not sufficient as intravenous administration in a phase II trial of PS-modified oligonucleotide found no clinical benefit for this therapeutic method despite initial promising in vitro and in vivo outcomes (4.4. Clinical Trials). Thus, despite advances and potential for therapy, Desgraves evidences unpredictability in the art for ASO use in brain malignancies.
The review article of Crooke (Crooke et al., J. Biol. Chem. (2021) 296 100416, pages 1-39) discusses that ASOs can have very different modification chemistries which individually effect stability, pharmacokinetics, pharmacodynamics and toxicology; physicochemical properties are reflected in quite significant differences in the pharmacokinetic behavior of ss phosphorothioate ASOs compared with ds phosphorothioate containing siRNAs; off-target degradation mediated effects are different between ASOs; and different cellular proteins bind respective ASOs which can affect uptake and intracellular distribution/localization. Crooke conclude that, “antisense technology is beginning to deliver on the promise envisioned more than 30 years ago though many questions remain to be answered”.
The amount of direction provided by inventor and existence of working examples
The specification goes on to disclose on pg. 4: ASO compositions… can include phosphorothioate (PS) linkages and/or locked nucleic acids (LNAs). The specification goes on to disclose on pg. 5: …can further comprise a polymeric micelle. In more specific embodiments, the polymeric micelle comprises a cerium oxide nanoparticle. The present application has working examples for four therapeutic antisense oligonucleotides but on pg. 22 the following is disclosed: The following ASOs were used: ASO targeting lnc-HLX-2-7(ASO-lnc-HLX-2- 7): + T*+G*+ A *G* A *G* A *T*T* A* A *T*C*T* A *G* A *T*+ T*+G*+C (SEQ ID NO:240) and control ASO targeting luciferase (ASO-Luc): +T*+C*+G*A*A*G*T*A*C*T*C*A*G*C*G*T*A*A*+G*+T*+T (SEQ IDNO:241).
In Vitro Embodiments
The specification discloses the following: Cell Proliferation, Apoptosis, and 3D Colony Formation Assays following knock down of MYC by siRNA in D425 Med and MED211 cells, which decreased the expression of both MYC and lnc-HLX-2-7 (FIG. 4A); overexpression of lnc-HLX-2-7 suppressed cell growth inhibition and downregulation of MYC by JQI (FIG. 11). IPA analysis revealed that lnc- HLX-2-7 knockdown preferentially regulated genes associated cell viability (FIG. 5B);
ASOs to inhibit lnc-HLX-2-7 expression in D425 Med and MED211 MB cells: Transfection with ASO-lnc-HLX-2-7 significantly decreased lnc-HLX-2-7 expression compared with controls (ASO-Luc) in both cell lines (P < 0.01; FIG. 2A), which significantly suppressed MB cell growth and induced apoptosis (P < 0.01; FIG. 2B, C); HLX expression was significantly reduced in D425 Med and MED211 cells following treatment with ASO-lnc-HLX-2-7 (FIG. 8). Lnc-HLX-2-7 CRISPR/Cas9 Knockdown in D425 Med Cells. Ingenuity Pathway Analysis shows lnc-HLX-2-7 knockdown preferentially affected genes associated with cell death (FIG. 12B). Of note, upstream regulator analysis showed that these genes contribute to important cancer pathways, including MYC, KRAS, HIF1A, and EGFR signaling (FIG. 12C). The present Results reported vast differences in the four ASO’s respective abilities to downregulate lnc-HLX-2-7. See Fig. 48. ASOs targeting overlapping regions (ASO2 vs. ASO3) also provided significantly different levels (e.g., almost a 2-fold difference) in target inhibition. ASO2 is targeted to nucleotides 480-500 of SEQ ID NO:200; ASO3 is targeted to nucleotides 468-488 of SEQ ID NO:200.
In Vivo Embodiments
Medulloblastoma Xenografts (Intracranial) (FIG. 3E) demonstrate that lnc-HLX-2-7 regulates tumor growth in vivo and may function as an oncogene. D425 Med and MED211 control cells and D425 Med and MED211-lnc-HLX-2-7-sgRNA cells were preinfected with a lentivirus containing a luciferase reporter. For an RNA Fluorescence In Situ Hybridization, Lnc-HLX-2-7 was found to be expressed in D425 Med mouse xenografts but not normal brain (FIG. 16). Applicants practice intravenous injection of ASO3 (LNA gapmer) (Fig. 47).
At the time of invention, the skilled artisan would have to use undue experimentation to make and/or use the embodiments within the scope of the invention.
Quantity of Experimentation needed
Successful results for 3/4ths of the LNA gapmer design style ASO tested, with variable results, does not reasonably extrapolate to successful results for any/all ASOs to different regions within the target gene without an undue amount of experimentation.
The level of skill required to make and/or use the instant invention would likely require many years of professional experience conducting research in the art (e.g., medicine, pharmaceutical science, biology, biochemistry, medicinal chemistry, etc.) as well as an advanced educational degree (e.g., M.D. and/or Ph.D.) commensurate in level with the advanced techniques involved in the preparation and/or use of the instant invention.
An unduly extensive amount of experimentation would be required for one of ordinary skill in the art to make and use an oligonucleotide composition for treating Grade III medulloblastoma.
Conclusion of Lack of Scope of Enablement
MPEP 2164.01(a) states, “A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the Specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557,1562,27 USPQ2d 1510, 1513 (Fed. Cir. 1993).” That conclusion is clearly justified here in view of the analysis above pursuant to In re Wands. The Wands Factors have been weighed and favor and support undue experimentation. In other words, one skilled in the art could not practice the full scope of the claimed invention without undue experimentation.
Hence, while ASO design and screening assays were routine in the prior art, practicing the claimed medulloblastoma treatment method was not routine or conventional or predictable. Further, the single species ASO (LNA gapmer) in the method of reducing Grade III medulloblastoma size/growth is not commensurate in scope with the claimed method as recited.
In view of the breadth of the claims, the lack of guidance, the unpredictability in the art, and the lack of working examples, the instant Specification is not found to be enabling over the full breadth. It would require undue experimentation and making a substantial inventive contribution for the skilled artisan to discover how to make and/or use the claimed invention over its full scope.
Claim Interpretation
The claims of the present invention recite antisense oligonucleotides (ASOs). The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the Specification as it would be understood by one of ordinary skill in the art. For examination purposes, the Examiner will interpret ASOs to include, encompass and embrace single-stranded antisense oligonucleotides that elicit a reaction through an RNase H mechanism and double-stranded antisense oligonucleotides that elicit a reaction via Ago2 (e.g. siRNAs). For further explanation, see Crooke et al. (J. Biol. Chem. (2021) 296 100416, pages 1-39).
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 18-23 and 12 are rejected under 35 U.S.C. § 101 because the claimed invention is directed to judicial exception (i.e., a law of nature, natural phenomenon, or an abstract idea) without significantly more. The claims are drawn to an antisense oligonucleotide (ASO) comprising a nucleotide sequence of 10 to 30 nucleotides in length that is complementary to a nucleic acid sequence within an angiopoietin like 2 (LHX-2-7) transcript. As outlined below, this judicial exception is not integrated into a practical application, and does not include additional elements that are sufficient to amount to significantly more than the judicial exception.
Subject Matter Eligibility Test for Products and Processes – Claim 18
Step 1 – Is the Claim to a Process, Machine, Manufacture, or Composition of Matter? YES
Claim 18 is directed to an ASO which is a composition of matter. The claims are directed to a statutory category.
Step 2A, Prong One – Does the Claim Recite an Abstract Idea, Law of Nature, or Natural Phenomenon? YES
Laws of nature and natural phenomena, as identified by the courts, include naturally occurring principles/relations and nature-based products that are naturally occurring or that do not have markedly different characteristics compared to what occurs in nature. MPEP 2106.04(c) outlines the markedly different characteristics analysis.
Claim 18 is directed to an antisense oligonucleotide (ASO) comprising a nucleotide sequence of 20 to 40 nucleotides in length that is complementary to (targets) a nucleic acid sequence within an lnc-HLX-2-7 (SEQ ID NO: 200) transcript. No limiting definition of ASO is provided. However, on pg. 19, the following is disclosed: In other embodiments, expression of the target can be disrupted using RNA interference technology including, but not limited to, a short interfering RNA (siRNA) molecule, a microRNA (miRNA) molecule, or an antisense molecule. Therefore, the term “antisense oligonucleotide (ASO)” is being given the BRI of oligonucleotides capable of modulating expression of a target gene by hybridizing to a target nucleic acid. The closest naturally-occurring counterpart to the claimed ASO is a portion of the human DNA encoding a human hLX transcript; i.e., non-coding /non-transcribed strand of DNA.
MPEP 2106.04(c)(II)(C)(1) provides an exemplary analysis relevant to the instant claims:
“In Ambry Genetics, the court identified claimed DNA fragments known as “primers” as products of nature, because they lacked markedly different characteristics. University of Utah Research Foundation v. Ambry Genetics Corp., 774 F.3d 755, 113 USPQ2d 1241 (Fed. Cir. 2014). The claimed primers were single-stranded pieces of DNA, each of which corresponded to a naturally occurring double-stranded DNA sequence in or near the BRCA genes. The patentee argued that these primers had markedly different structural characteristics from the natural DNA, because the primers were synthetically created and because “single-stranded DNA cannot be found in the human body”. The court disagreed, concluding that the primers’ structural characteristics were not markedly different than the corresponding strands of DNA in nature, because the primers and their counterparts had the same genetic structure and nucleotide sequence. 774 F.3d at 760, 113 USPQ2d at 1243-44. The patentee also argued that the primers had a different function than when they are part of the DNA strand because when isolated as a primer, a primer can be used as a starting material for a DNA polymerization process. The court disagreed, because this ability to serve as a starting material is innate to DNA itself, and was not created or altered by the patentee:
In fact, the naturally occurring genetic sequences at issue here do not perform a significantly new function. Rather, the naturally occurring material is used to form the first step in a chain reaction--a function that is performed because the primer maintains the exact same nucleotide sequence as the relevant portion of the naturally occurring sequence. One of the primary functions of DNA’s structure in nature is that complementary nucleotide sequences bind to each other. It is this same function that is exploited here--the primer binds to its complementary nucleotide sequence. Thus, just as in nature, primers utilize the innate ability of DNA to bind to itself.
Ambry Genetics, 774 F.3d at 760-61, 113 USPQ2d at 1244. In sum, because the characteristics of the claimed primers were innate to naturally occurring DNA, they lacked markedly different characteristics from nature and were thus product of nature exceptions. A similar result was reached in Marden, where the court held a claim to ductile vanadium ineligible, because the “ductility or malleability of vanadium is . . . one of its inherent characteristics and not a characteristic given to it by virtue of a new combination with other materials or which characteristic is brought about by some chemical reaction or agency which changes its inherent characteristics”. In re Marden, 47 F.2d 958, 959, 18 CCPA 1057, 1060, 8 USPQ 347, 349 (CCPA 1931).” (emphasis added).
The claimed ASO requires a nucleotide sequence between 20-40nts in length which is complementary to a sequence within a LHX-2-7 transcript. The naturally-occurring non-coding strand of the human DNA encoding the LHX-2-7 transcript is 100% complementary to the LHX-2-7 ASO. Thus, a portion of the non-coding strand of human DNA encoding a LHX-2-7 transcript meets the structural requirements of the claimed ASO. As noted in the example in MPEP 2106.04(c)(II)(C)(1) above, attention must also be paid to the functional characteristics of the claimed oligonucleotides. Based on the BRI, the term “antisense oligonucleotide (ASO)” reads on a nucleic acid, which by virtue of its nucleotide sequence, performs the function of hybridizing to, and inhibiting expression of a target RNA (i.e., LHX-2-7 transcript). The portions of the naturally-occurring non-coding strand of human DNA encoding the LHX-2-7 transcript meets the structural requirements for the complementary sequence of the claimed ASO, and therefore, are presumed to inherently have the same functional characteristics as the claimed ASO. Accordingly, the claimed ASO is not markedly different from its naturally occurring counterpart – a portion of the non-coding strand of human DNA encoding a human LHX-2-7 transcript. Thus, claim 18 recites a product of nature judicial exception.
Step 2A, Prong Two – Does the Claim Recite Additional Elements that Integrate the Judicial Exception into a Practical Application? NO
The Supreme Court has long distinguished between principles themselves, which are not patent eligible, and the integration of those principles into practical applications, which are patent eligible. The phrase "integration into a practical application" requires an additional element or a combination of additional elements in the claim to apply, rely on, or use the judicial exception in a manner that imposes a meaningful limit on the judicial exception, such that it is more than a drafting effort designed to monopolize the exception.
In the instant case, claim 18 does not recite any elements in addition to the judicial exception (i.e., natural product) that would integrate the natural product into a practical application.
Step 2B – Does the Claim Recite Additional Elements that Amount to Significantly More than the Judicial Exception? NO
The Supreme Court has identified a number of considerations for determining whether a claim with additional elements amounts to "significantly more" than the judicial exception(s) itself. The claim as a whole is evaluated as to whether it amounts to significantly more than the recited exception, i.e., whether any additional element, or combination of additional elements, adds an inventive concept to the claim (MPEP 2106.05).
As stated above, claim 18 does not recite any elements in addition to the judicial exception (i.e., natural product). There are no additional elements to amount to significantly more than the judicial exception.
Dependent Claims – Claims 19-23 and 12
Regarding claim 19, the claim is interpreted as requiring that the entire ASO be complementary to certain recited ranges within SEQ ID NO: 200, which is a nucleic acid sequence within a LHX-2-7 transcript; i.e., the claim limits the regions within the LHX-2-7 transcript to which the ASO sequence must be complementary. As discussed above, the naturally-occurring counterpart to the claimed invention – a portion of the non-coding strand of human DNA encoding a human LHX-2-7 transcript – is 100% complementary to a ASO targeting the LHX-2-7 transcript. The claim does not recite any additional elements. Thus, claim 19 is still not markedly different from the naturally-occurring counterpart, and recites a judicial exception without additional elements which integrate the judicial exception into a practical application, or amount to significantly more than the judicial exception.
Regarding claim 20, the claim further defines the SEQ ID Nos of the limited regions within the LHX-2-7 transcript to which the ASO must be complementary. Thus, the naturally-occurring counterpart to the claimed invention – a portion of the non-coding strand of human DNA encoding a human LHX-2-7 transcript – comprises a 20-40nt ASO 100% complementary to a nucleic acid sequence within the LHX-2-7 transcript of SEQ ID NO: 200. The claim does not recite any additional elements. Thus, claim 20 is still not markedly different from the naturally-occurring counterpart, and recites a judicial exception without additional elements which integrate the judicial exception into a practical application, or amount to significantly more than the judicial exception.
Regarding claims 21-22, these claims are similar in scope to claims 19-20 as discussed above. Thus, claims 21-22 are still not markedly different from their naturally-occurring counterpart, and recite a judicial exception without additional elements which integrate the judicial exception into a practical application, or amount to significantly more than the judicial exception.
Regarding claim 12, claim 12 is being interpreted as the composition of claim 19 comprised in a polymeric micelle. Since cells have polymeric micelles (vesicles), the closest naturally-occurring counterpart to the claimed invention is a cell (comprising the DNA and the vesicles). A cell is a product of nature. The claim does not recite any additional elements. Thus, claim 12 is still not markedly different from the naturally-occurring counterpart, and recites a judicial exception without additional elements which integrate the judicial exception into a practical application, or amount to significantly more than the judicial exception.
Regarding claim 23, claim 23 is similar in scope to claim 12. Thus, claim 23 is still not markedly different from its naturally-occurring counterpart, in this case, a portion of the non-coding strand of human DNA encoding a human LHX-2-7 transcript, and recites a judicial exception without additional elements which integrate the judicial exception into a practical application, or amount to significantly more than the judicial exception.
Therefore claims 18-23 and 12 are rejected under 35 U.S.C. § 101 because they are directed to a judicial exception.
Eligible under §101: Dependent Claims 13 and 24
Regarding claims 13 and 24, the claims are directed to a composition comprising an antisense oligonucleotide (ASO) that is complementary to (targets) a nucleic acid sequence within an lnc-HLX-2-7 (SEQ ID NO: 200) transcript where in the composition further comprises a polymeric micelle, where in the polymeric micelle comprises cerium oxide nanoparticle.
The closest naturally-occurring counterpart to a composition within a polymeric micelle that comprises cerium oxide nanoparticle is a cell. Accordingly, the “cerium oxide nanoparticle” imparts characteristics to the composition such that it has markedly different characteristics than a cell. (STEP 1: YES). Therefore, claims 13 and 24 are eligible under prong one.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 18 is rejected under 35 U.S.C. 102(a)(2) as being anticipated by Lee (US/9328346).
Lee teach an antisense oligonucleotide that is 27 nucleotides long, comprising the sequence consisting of SEQ ID No. 156175 (see alignment below) which is 100% complementary to a portion of SEQ ID NO: 200. Therefore, the sequence taught by Lee is an ASO that targets a 20-40 nucleotide sequence of lnc-HLX-2-7 as required by claim 18.
RESULT 11
US-13-884-670A-156175/c
(NOTE: this sequence has 5 duplicates in the database searched.
See complete list at the end of this report)
Sequence 156175, US/13884670A
Patent No. 9328346
GENERAL INFORMATION
APPLICANT: Lee, et al.
TITLE OF INVENTION: Polycomb-Associated Non-Coding RNAs
FILE REFERENCE: 00786-0775P04/MGH20865
CURRENT APPLICATION NUMBER: US/13/884,670A
CURRENT FILING DATE: 2014-02-21
PRIOR APPLICATION NUMBER: 61/412,862
PRIOR FILING DATE: 2010-11-12
PRIOR APPLICATION NUMBER: 61/425,174
PRIOR FILING DATE: 2010-12-20
PRIOR APPLICATION NUMBER: 61/512,754
PRIOR FILING DATE: 2011-07-28
NUMBER OF SEQ ID NOS: 194345
SEQ ID NO 156175
LENGTH: 27
TYPE: DNA
ORGANISM: Homo sapiens
Query Match 5.2%; Score 27; Length 27;
Score over Length 100.0%;
Best Local Similarity 100.0%;
Matches 27; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 65 CACACACACACACACACACACACACAC 91
|||||||||||||||||||||||||||
Db 27 CACACACACACACACACACACACACAC 1
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 14-17 and 1-9 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, and 5-9 of issued U.S. Application No. 17642752 (reference application) in view of Hagedorn (Hagedorn et al., Drug Discovery Today, Volume 23, Number 1, January 2018), Sezgin-bayindir (Sezgin-bayindir et al., Journal of Drug Delivery Science and Technology 36 (2016) 120e129), and Beier (Beier et al., Neuro-Oncology 20(3), 400–410, 2018).
Although the claims at issue are not identical, they are not patentably distinct from each other as discussed below.
Regarding claims 1, 14, and 15: while the preamble of instant claims 1, 14 and 15 differs from the preamble of claim 1 of reference application, the steps of the claims require hybridizing a sequence of nucleotides to a target, which is lnc-HLX-2-7, therefore reads on the same method.
Instant Independent Claims only
17642752 Claims
1. A method for treating medulloblastoma in a patient comprising the step of administering a composition comprising an antisense oligonucleotides (ASO) targeting long non- coding ribonucleic acid HLX-2-7 (lnc-HLX-2-7).
1. A method comprising detecting long non-coding (lnc) RNA HLX2-7 in a biological sample obtained from a patient having or suspected of having medulloblastoma wherein the detecting step is performed using RNA fluorescence in situ hybridization (FISH) assay.
3. The method of claim 1, wherein the biological sample is a tissue sample.
14. A method comprising the steps of: (a) detecting overexpression of Inc-HLX-2-7 in a sample obtained from a patient having medulloblastoma; and (b) treating the patient with a composition comprising a polymeric micelle and an ASO that targets lnc-HLX-2-7.
5. wherein the FISH assay comprises oligonucleotide probes that hybridize to lncHLX2-7 and branched DNA signal amplification.
6. wherein the probes comprise at least one of SEQ ID NOS:3-4 and 8-21.
15. A method comprising the step of administering a composition comprising a polymeric micelle and an ASO that targets lnc-HLX-2-7 to a patient diagnosed with group III medulloblastoma.
7. wherein the probes comprise SEQ ID NOS:3-4 and 8- 21.
8. wherein the probes further comprise at least one of SEQ ID NOS:5-7.
18. A composition comprising an ASO that targets a 20-40 nucleotide sequence of Inc-HLX-2-7 (SEQ ID NO:200).
9. wherein the probes further comprise SEQ ID NOS:5-7.
As per the description in the reference app, “a probe set of oligonucleotide pairs hybridizes to the target RNA”. The sequence listing of the ref app discloses SEQ ID NOs: 3 and 5-19 are within 20-40 nucleotides and complementary to instant SEQ ID NO: 200; i.e., targeting lnc-HLX-2-7, as required by instant app dependent claims.
For e.g., SEQ ID NO: 16 (28ntds) of ref app is identical to instant SEQ ID NO: 282:
US-17-642-752-16
Query Match 78.3%; Score 18; DB 1; Length 28;
Best Local Similarity 100.0%;
Matches 18; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 GTTGTTTTAAGTCACTAA 18
||||||||||||||||||
Db 11 GTTGTTTTAAGTCACTAA 28
The reference app does not teach “a method of treatment”.
However, before the effective filing date of instant invention, Hagedorn had reviewed the state of the art with respect to lnc RNA inhibitors.
Hagedorn teaches “A rational strategy to target RNA is by synthetic oligonucleotides… inhibitory effects induced by the oligonucleotide binding complement can be executed rapidly and effectively.” (2nd para, pg. 102; Fig. 1 and legend). Thus, the basic requirement for an inhibitory oligonucleotide is: complementarity. Such inhibitory oligonucleotides are the mainstay of RNA therapeutics. See further recitation from Hagedorn: The standard, target-centric, model of RNA drug discovery begins with the identification of a target known to be causally involved in a particular disease (Fig. 6a). From the sequence of the RNA target, libraries of complementary AONs can then be designed and synthesized (pg. 109, right column, first para).
Hagedorn does not teach polymeric micelles or cisplatin.
However, before the effective filing date of instant invention, Sezgin-bayindir had taught polymeric micelles may be formed from various chemicals and can be used for efficient delivery of cargo to the brain (title). Specifically Sezgin-bayindir taught polymeric micelles are considered as a more beneficial approach to drug delivery since the drug and barrier properties can be preserved (pg. 120, R col., 1st para). Sezgin-bayindir taught that the prolonged circulation time of polymeric micelles in blood leads to controlled drug release thus, improves the bioavailability (pg. 121, L col., 2nd para). Finally, the self-assembly phenomena of polymers in aqueous media is an efficient way for preparing nanosized drug delivery systems which can carry a variety of drugs (pg. 122, R col., last three paras).
Beier had taught chemotherapy combination therapy for medulloblastoma (title). Beier had taught that previous studies from Packer and coworkers indicate that radiotherapy plus concomitant and adjuvant chemotherapy is superior to radiotherapy alone in children (pg. 407, L col, last para), thus making a case for an additional therapy, such as cisplatin in the treatment of medulloblastoma. Specifically Beier taught the NOA-07 trial combined craniospinal irradiation with vincristine, followed by 8 cycles of cisplatin, lomustine, and vincristine (abstract). Beier taught that the regimen and schedule “was justified retrospectively by upcoming data that suggest that a decreased number of treatment cycles is not decisive for PFS or OS in children with average-risk medulloblastoma.” (pg. 406, R col, 1st para). Therefore, cisplatin in combination therapy is a mainstay treatment for medulloblastoma.
It would have been obvious to one of ordinary skill, in the art at the time, to utilize the probes of the reference app in a method of treating Group III Medulloblastoma because the reference app teaches that a probe to lnc-HLX-2-7 hybridizes to the target RNA (see description above) and Hagedorn teaches that the basic requirement for a therapeutic ASO is complementarity (hybridization) with the target. It would have also been obvious to one of ordinary skill, in the art at the time, to incorporate the probes of the reference app and cisplatin into polymeric micelles because both Sezgin-bayindir and Beier taught it would be beneficial to do so in the treatment of medulloblastoma.
Therefore, the claims at issue are not identical, and also not patentably distinct from each other because the instant application is made obvious by the cited application in view of Hagedorn, Sezgin-bayindir, and Beier.
Claims 18-22 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, and 5-9 of issued U.S. Application No. 17642752 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because instant application claims are anticipated by the reference claims.
While the preamble of instant claim 18 (a composition comprising…) differs from the preamble of claim 1 (a method comprising…) of reference application, the reference application requires a sequence of nucleotides that specifically bind to (hybridize to) lnc-HLX-2-7, therefore reads on the same composition as required by instant claims under consideration.
Claims 12-13 and 23-24 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, and 5-9 of issued U.S. Application No. 17642752 (reference application) as applied to claims 18-22 above and further in view of Hagedorn (Hagedorn et al., Drug Discovery Today, Volume 23, Number 1, January 2018) and Xu (Xu and Qu, NPG Asia Materials volume 6, e90, 2014).
Although the claims at issue are not identical, they are not patentably distinct from each other as discussed below.
Hagedorn’s teachings taught above are incorporated herein.
Neither reference app nor Hagedorn teach cerium oxide nanoparticle.
However, before the effective filing date of instant invention, Xu had taught a Cerium oxide nanoparticle’s versatility for biological applications (title). Specifically Xu taught cerium oxide nanoparticle as drug delivery devices and scaffold (pg.11, R col, 2nd para). Xu taught that cerium oxide nanoparticles are cytotoxic to cancer cells. Therefore, “Combining the two properties increases CeONP’s potential application in biotechnology.” (pg.11, R col, 2nd para).
It would have been obvious to one of ordinary skill, in the art at the time, to incorporate the probes of the reference app into cerium oxide nanoparticles because Xu taught it would be beneficial to do so, especially in the treatment of cancer.
Allowable Subject Matter
The closest prior art is Lin (Lin et al., Nature. 2016 February 04; 530(7588): 57–62.).Lin teach Group III medulloblastoma is characterized by active cis-regulatory circuitry involving Super Enhancers (SE) regulating expression of “a large fraction of established medulloblastoma signature genes (32%; Supplemental Table S3), as well as novel candidates (Figure 3a–c)”. Amongst the genes showing increased expression are MYC and HLX.
It would have been obvious to one of ordinary skill, in the art at the time, to make an antisense to HLX to decrease levels of the latter because it was known in the art that natural antisense transcripts interfere with the expression of the corresponding sense transcript, such that the antisense transcript and sense transcript may have inverse expression patterns (sections 3-4, pg. 178, Su et al., 2010, Biochemical and Biophysical Research Communications, 396(2010), p. 177-181).
However, instant concept is contrary to what would have been obvious at the time of filing, as instant is drawn to inhibiting expression of the natural antisense transcript, rather than increasing levels of the natural antisense transcripts
Sequences identical in length and % complementarity to SEQ ID NOs: 240 (modified) and 287, drawn to ASO targeting specific region nucleotides 466-488 of lnc-HLX-2-7 (SEQ ID NO: 200), only returned Applicants own work.
Kesherwani (Kesherwani et al., BMC Medical Genomics (2020) 13:87) review the state of the Art around the time of filing of instant application. Group 3 Medulloblastoma (MB) was known at the time to be mainly MYC-driven. Therefore, a subgroup of genetic aberrations in MYC regulated genes was identified. lnc-HLX-2-7 was not implicated in Group 3 Medulloblastoma (MB) at the time of filing.
Conclusion
No claims are allowed.
Correspondence
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/SHABANA S MEYERING/Examiner, Art Unit 1635
/SHABANA S MEYERING/Examiner, Art Unit 1635
/CATHERINE KONOPKA/Primary Examiner, Art Unit 1635
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