DETAILED ACTION
Receipt of Arguments/Remarks filed on September 8 2026 is acknowledged. Claims 4, 11 and 19 were/stand cancelled. Claims 20-27 were added. Claims 1, 5 and 7 were amended. Claims 1-3, 5-10, 12-18 and 20-27 are pending. Claims 8-9 and 12-17 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 February 20 2026. Claims 1-3, 5-7, 10, 18 and 20-27 are directed to the elected invention.
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 .
Withdrawn Objections/Rejections
The amendments filed September 8 2026 are sufficient to overcome the objection to the drawings. The drawings now recite Fig. instead of figures.
The cancellation of claim 19 has rendered the objection moot.
The amendment filed September 8 2026 are sufficient to overcome the objection to claim 7 as the abbreviations is spelt out.
The amendments filed September 8 2026 are sufficient to overcome the rejection of claims 1-7, 10 and 18-19 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. The claims recite the miRNA are in isolated form and are not included in a secreted extracellular vesicle or cell clarifying the scope of isolated.
The amendments filed September 8 2026 are sufficient to overcome the rejection of claims 1-4 under 35 USC 102 over Jauliac et al.; and the rejection of claim 6 under 35 U.S.C. 103 over Jauliac et al. in view of Rigoutsos et al. Firstly, claim 4 was cancelled rendering the rejection moot. In light of the amendment to claim 1, claims 1-3 and 6 are interpreted as excluding secreted extracellular vesicles which are required by Jauliac et al.
New and Modified Rejections Necessitated by the
Amendments filed September 8 2026
Claim Interpretation
Claims 20 and 22 and the claims that depend from claims 20 and 22 contain the transitional language “consisting essentially of”. For the purposes of searching for and applying prior art under 35 U.S.C. 102 and 103, absent a clear indication in the specification or claims of what the basic and novel characteristics actually are, “consisting essentially of” will be construed as equivalent to “comprising.” If an applicant contends that additional steps or materials in the prior art are excluded by the recitation of “consisting essentially of,” applicant has the burden of showing that the introduction of additional steps or components would materially change the characteristics of applicant's invention. PPG Industries Inc. V Guardian Industries Corp. 48 USPQ2d 1351 (Fed. Cir. 1998) and In re De Lajarte 337 F.2d 870, 143 USPQ 256 (CCPA 1964) See MPEP 2111.03.
The specification states that: ““Consisting essentially of” shall mean excluding other components or steps of any essential significance. Thus, a composition “consisting essentially of” one or more components may further comprise only additional unrecited components without essential significance.” (page 5). However, the specification fails to indicate what is meant by “essential significance”.
Therefore, the instant specification does not define the term “consisting essentially of” in a manner that would allow one skilled in the art to determine what basic and novel characteristics are being materially affected.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-3, 5, 7, 10, 18 and 20-27 are rejected under 35 U.S.C. 101 because the claimed invention is directed to laws of nature and a natural phenomenon without significantly more.
The claims recite laws of nature and natural phenomena. These judicial exceptions are not integrated into a practical application and the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception as explained below:
Subject Matter Eligibility Guidance
A three-step inquiry has been established to determine subject matter eligibility under 35 U.S.C. 101, in accordance with MPEP § 2106:
Step (1). Is the claim directed to a process, machine, manufacture, or composition of matter?
Step (2A). Is the claim directed to a law of nature, natural phenomenon (product of nature), or an abstract idea?
Prong 1 – Does the claim recite a law of nature, natural phenomenon, or an
abstract idea?
Prong 2 – If the claim recites a judicial exception, does it recite additional elements that integrate the judicial exception into a practical application?
Limitations that are indicative of integration into a practical application include:
Improvements to the functioning of a computer, or to any other technology or technical field. See MPEP § 2106.05(a)
Applying the judicial exception with, or by use of, a particular machine. See MPEP § 2106.05(b)
Effecting a transformation or reduction of a particular article to a different state or thing. See MPEP § 2106.05(c)
Applying or using a judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition. See MPEP § 2106.05(d)
Applying or using the judicial exception in some other meaningful way beyond generally linking the use of the judicial exception to a particular technological environment, such that the claim as a whole is more than a drafting effort designed to monopolize the exception. See MPEP § 2106.05(e)
Step (2B). If the recited judicial exception is not integrated into a practical application, does the claim recite additional elements that amount to significantly different than the judicial exception such that they provide an inventive concept? This step includes evaluation of the same considerations under Step (2A), Prong 2, as well as two additional considerations:
Adding a specific limitation or combination of limitations that are not well-understood, routine, conventional activity in the field, which is indicative that an inventive concept may be present; and
Simply appending well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception, which is indicative that an inventive concept may not be present.
Analysis
Step (1): The answer to this step is yes since claims 1-3, 5, 7, 10, 18 and 20-27 are directed to a product (composition of matter), which is a statutory category.
Step (2A):
Product of Nature Definition
When a law of nature or natural phenomenon is claimed as a physical product, the courts have often referred to the exception as a "product of nature". See Ass’n for Molecular Pathology v. Myriad Genetics, Inc., 569 U.S. 576, 580, 106 USPQ2d 1972, 1975 (2013); University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 758-59, 113 USPQ2d 1241, 1243 (Fed. Cir. 2014). As explained in those decisions, products of nature are considered to be an exception because they tie up the use of naturally occurring things, but they have been labeled as both laws of nature and natural phenomena. See Myriad Genetics, Inc., 569 U.S. at 590-91, 106 USPQ2d at 1979.
Claim Analysis
Prong 1
The markedly different characteristics analysis is part of Step 2A Prong One, because the courts use this analysis to identify product of nature exceptions.
Claim 1: is directed to a miRNA composition comprising 11 isolated miRNA. Claims 20 and 22 recite similar composition consisting essentially of the miRNA. The specification (page 11) states that these 11 miRNAs are present in SEVs of cells expressing NFATC4 which indicates that these miRNA occur in nature. While the claim recites the miRNA are in an isolated form and are not included in a SEV or cell, this limitation does not result in a marked difference between the miRNA claimed and that is what is found in nature. Even if the miRNA were not to all occur together in nature, they are all individually naturally occurring. Nothing in the instant specification establishes an unexpected effect with the claimed combination, for example synergy, indicating that the claimed combination exhibits a markedly different characteristics from the naturally occurring counterpart. MPEP 2106.04(b) makes it clear: t is important to keep in mind that product of nature exceptions include both naturally occurring products and non-naturally occurring products that lack markedly different characteristics from any naturally occurring counterpart. See, e.g., Ambry Genetics, 774 F.3d at 760, 113 USPQ2d at 1244 ("Contrary to Myriad's argument, it makes no difference that the identified gene sequences are synthetically replicated. As the Supreme Court made clear, neither naturally occurring compositions of matter, nor synthetically created compositions that are structurally identical to the naturally occurring compositions, are patent eligible."). Thus, a synthetic, artificial, or non-naturally occurring product such as a cloned organism or a human-made hybrid plant is not automatically eligible because it was created by human ingenuity or intervention. See, e.g., In re Roslin Institute (Edinburgh), 750 F.3d 1333, 1337, 110 USPQ2d 1668, 1671-72 (Fed. Cir. 2014) (cloned sheep); cf. J.E.M. Ag Supply, Inc. v. Pioneer Hi-Bred Int’l, Inc., 534 U.S. 130-132, 60 USPQ2d 1868-69 (2001) (hybrid plant). Instead, the key to the eligibility of all non-naturally occurring products is whether they possess markedly different characteristics from any naturally occurring counterpart.
Claim 10 is directed to a pharmaceutical composition comprising the miRNA. This recitation “pharmaceutical composition” in the preamble does not structurally or functionally distinguish the instant claimed miRNA from their naturally occurring counterpart.
Claims 2, 21 and 23 are directed to the same miRNA combination at specific ratios which page 11 of the instant specification indicates were present in the SEVs of cells expressing NFATC4. Even if the ratios were not naturally found, absent a demonstration of a marketed difference, the ratio does not structurally or functionally distinguish the instantly claimed miRNAs from its naturally occurring counterpart.
Claim 3 recites the further inclusion of additional miRNA which are not distinguished from their naturally occurring counterpart.
Claims 5, 7 and 18 further include a delivery vector containing the miRNA. These delivery vectors are merely carriers for the miRNA. As set forth on page 11 of the instant specification the miRNA naturally occur in SEV indicating that claim 7 when compared to the closest natural product would not be structurally or functionally different. A delivery vector as claimed includes SEV which naturally occur with the miRNA.
Claims 24-25 recite the composition additionally contains a buffer which the claims recite include water. This does not result in a marked difference.
Claims 26-27 recite processes in which the SEV is loaded with the miRNA. These claims are directed to product by process limitations. However, they do not structurally change the resulting SEV with the miRNA. As set forth above, MPEP 2106.04(b) is clear even if the products are not naturally occurring if they lack a marked difference characteristic from any naturally occurring counterpart, then the product is not eligible.
Therefore, the answer to step 2A prong 1 is yes.
Claim 6, however, is deemed eligible as it is directed to a liposome loaded with the miRNA. This has been determined to be a carrier which has structural and physical characteristics that distinguish it from the closest counterpart in nature (see for example 28 of the 101 examples).
If the claim includes a nature-based product that does not exhibit markedly different characteristics from its naturally occurring counterpart in its natural state (as established above), then the claim recites a "product of nature" exception and requires further analysis in Step 2A Prong Two to determine whether the claim as a whole integrates the exception into a practical application.
Prong 2:
The Prong Two analysis considers the claim as a whole. That is, the limitations containing the judicial exception as well as the additional elements in the claim besides the judicial exception need to be evaluated together to determine whether the claim integrates the judicial exception into a practical application. The instant claims do not integrate the additional elements into a practical application. Examples of a practical application would be treating cancer as set forth in the unexamined/unelected claims.
Therefore, the answer to step 2A prong 2 is No.
Step (2B):
Since no additional elements except those identified above are present and those are naturally occurring with the miRNA as well, there are no additional elements.
Therefore, the answer to step (2B) is No.
Conclusion
Claims 1-3, 5, 7, 10, 18 and 20-27 are directed to a judicial exception and do not qualify as eligible subject matter under 35 U.S.C. § 101.
Response to Arguments
Applicant’s arguments filed September 8 2026 have been fully considered but they are not persuasive.
Applicant argue that claim 1 was amended to recite that the 11 miRNA are in isolated form and not included in a secreted extracellular vesicle or cell. Accordingly, the 11 miRNA are not directed merely to miRNA as they may occur in nature, they require technically prepared, isolated, miRNA compositions separated from the cellular and vesicular structure in which miRNA are found in nature. As such the miRNA composition results from deliberate human intervention and does not exist in nature in the claimed form. It is argued that these technical and structural characteristics distinguish the claimed subject matter form naturally occurring SEVs and other biological materials. It is argued that new claims 20- 24 recite consisting essentially of and amended claims 5-7 further require delivery vectors loaded ex vivo and claims 25-26 define technical ex vivo loading procedures. The ex vivo loading processes created engineered delivery systems having defined miRNA cargo and are structurally and functionally distinct from naturally secreted extracellular vesicles.
Regarding Applicant’s arguments, mere isolation or human intervention is not sufficient to result in a natural product being eligible under 101. While the isolation of the miRNA might result in the lack of a cell or an SEV as the miRNA are found in nature, the claimed miRNA has the same nucleic acid sequences as those found in nature and have no different functional characteristics. Therefore, while the miRNA might be different (i.e. no cell or SEV) it is not markedly different, which is the requirement set forth in the MPEP. Nothing in Applicants arguments clearly indicate how the miRNA are structurally or functionally different and merely make the statement. Thus, there is no evidence either presented in the arguments or the specification that establishes that the miRNA have any difference structurally or functionally and thus the claims are not eligible. The examiner directs Applicants to natural product example 7 under the 101 guidance as an example of an isolated nucleic acid not being deemed patent eligible for additional discussion. Regarding claims 5-7 as amended, the mere inclusion of the word ex vivo does not automatically make a natural product markedly different than the naturally occurring counterpart. These claims are directed to delivery vectors, aka carriers, for the miRNA. While the miRNA composition may be loaded into the delivery vector or SEV ex vivo the resulting product the vector with the SEV is not structurally or functionally distinguished from the naturally occurring SEV with the miRNA. Regarding new claims 24-25, a specific buffer claimed is water. This does not structurally or functionally distinguish the instant composition from the naturally occurring counterpart as there is no indication that mixing water with the miRNA changes the structure, function or other properties of the miRNA or water. Furthermore, the use of a carrier is well-understood, routine and conventional. See 101 example 28 for additional discussion. Regarding claims 26-27, these claims are directed to product by process. Thus, eligibility is considered based on the final product. If Applicants show that the process would result in a product that is structurally or functionally different and thus would result in a marked difference from the corresponding natural product, then this could serve the basis for eligibility. However, currently, nothing has been demonstrated that the result SEVs loaded with the miRNA possess a marked difference.
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 7 and 24-27 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 7 and 26-27 as currently written are vague and indefinite. Claim 7 depends from claim 1 which expressly states that the miRNA are not included in a secreted extracellular vesicle or cell. However, claim 7 expressly recites the miRNA composition is loaded in a secreted extracellular vesicle. It is unclear how the limitations of claim 1 can be met, i.e. not included in a secreted extracellular vesicle, and also included in an extracellular vesicle. The limitations of claim 7 are in direct conflict of claim 1. This is same with claims 26-27, while the claims recite processes steps to obtain the SEVs loaded with the miRNA composition, the resulting product is an SEV loaded with the miRNAs which is excluded by claim 1.
Claims 24- 25 as current written is vague and indefinite. Claim 25 recites the buffer is water. The instant specification does not provide a limiting definition of buffer; therefore, the BRI of the claim is the conventional meaning of the claim. As taught by LibreTexts a buffer is a solution that can resist pH change upon the addition of acidic or basic components. A buffer must consist of a weak conjugate acid-base pair. Thus, water is not a buffer as conventionally defined. While Applicants may be their own lexicographer, terms used contrary to their ordinary meaning must be clearly defined in the written description. See MPEP 2173.05(a). Since Applicants are reciting water as a buffer and under its conventional definition water would not constitute a buffer, this creates confusion as to the scope of the claimed buffer.
Claim Rejections - 35 USC § 112
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.
Claims 7 and 26-27 are 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.
Claims 7 and 26-27 all ultimately depend from claim 1 which recites the miRNA are not included in a secreted extracellular vesicle. However, claims 7 and 26-27 all require the miRNA to be part of a secreted extracellular vesicle. Thus, claims 7 and 26-27 are broader in scope than the claim from which they depend.
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.
Claim Rejections - 35 USC § 102
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)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 5, 7, 10, 18, and 26-27 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Jauliac et al. (WO2017167788, cited on PTO Form 1449).
The instant application claims a delivery vector loaded ex vivo with the miRNA composition.
While the claims are indefinite for the reasons set forth above, claims 5, 7 and dependents are interpreted as requiring a SEV with the miRNA composition.
Jauliac et al. is directed to composition comprising secreted extracellular vesicles of cells expressing NFATC4 useful for the treatment of cancer. Claimed is a composition comprising secreted extracellular vesicles (SEV) of cells expressing nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 4 (NFATC4) for use in the treatment of cancer. The SEV have been purified from cancer cells (claims 1-2). It is taught that SEV contain not only proteins but also functional mRNAs, long non-coding RNAs and miRNAs (page 2, lines 10-12). Example 1 of Jauliac et al. corresponds to example 1 of the instant specification with the same cell line, MDA-MB-231 and T47D being utilized (see pages 43-54).
The specification (page 11) makes it clear that the 11 miRNA claimed were present in specific ratios in the SEVs of cells expressing NFATC4. Since Jauliac et al. expressly teaches SEVs of cells expressing NFATC4, it would appear based on the instant specification that the SEVs would necessarily possess the claimed 11 miRNA in the claimed ratio. The examiner directs applicant's attention to MPEP 2112, section I: "[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art's functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977).
Regarding claims 5, 7 and 18, SEV are claimed as a delivery vector and thus read on the claimed delivery vector loaded with the miRNA. It is noted that the recitation “ex vivo” is interpreted as a product-by-process limitation (see below) and this does not distinguish the instant claims from the prior art.
Regarding claims 26-27, Note MPEP 2113: “[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.” In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985). The MPEP also indicates that “the structure implied by the process steps should be considered when assessing the patentability of product-by-process claims over the prior art, especially where the product can only be defined by the process steps by which the product is made, or where the manufacturing process steps would be expected to impart distinctive structural characteristics to the final product. See, e.g., In re Garnero, 412 F.2d 276, 279, 162 USPQ 221, 223 (CCPA 1979). “In determining validity of a product-by-process claim, the focus is on the product and not the process of making it.” Amgen Inc. v. F. Hoffman-La Roche Ltd., 580 F.3d 1340, 1369 (Fed.Cir.2009). The process of making is only relevant “if the process by which a product is made imparts ‘structural and functional differences’ distinguishing the claimed product from the prior art” Greenliant Systems, Inc. v. XicorLLC, 692 F.3d 1261, 1268 (Fed. Cir. 2012). Here the resulting product is SEV with the miRNA which is suggested by Jauliac et al.
Response to Arguments
Applicant’s arguments filed September 8 2026 have been fully considered but they are not persuasive.
Applicant argues that Jauliac describes naturally secreted extracellular vesicles. In contrast the present claims require multiple technical features that are not disclosed of suggested in Jauliac. Claims 5-7 recite delivery vectors loaded ex vivo with miRNA composition and claims 25-27 further define ex vivo loading procedures.
While Applicants argument with regards to claim 1 and 6 are persuasive, the recitation ex vivo does not structurally distinguish the instant claims from the prior art. There is nothing in the claims that recites any particular structural requirements of the secreted extracellular vesicle which distinguishes from those taught in Jauliac. Thus, for the claims that require the miRNA composition loaded in SEVs, Jauliac is still prior art.
Claim Rejections - 35 USC § 103
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 of this title, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-3, 5-6, 10, 18, 20-21, and 24-25 are rejected under 35 U.S.C. 103 as being unpatentable over Rigoutsos et al. (WO2014179765, cited in the Office action mailed on December 23 2025).
Applicant Claims
The instant application claims a miRNA composition comprising the following miRNAs: hsa-miR-3 195, hsa-miR- 1246, hsa-miR-188-3p, hsa-miR-16-5p, hsa-miR- 196a-3p, hsa- miR-32-5p, hsa-miR-4532, hsa-miR-4792, hsa-miR-4488, hsa-miR-326, and hsa-miR-7704, wherein said miRNAs are in an isolated form and are not included in a secreted extracellular vesicle or cell.
The instant application claims a miRNA composition consisting essentially of the following i miRNAs: hsa-miR-3 195, hsa-miR- 1246, hsa-miR-188-3p, hsa-miR-16-5p, hsa-miR- 196a-3p, hsa- miR-32-5p, hsa-miR-4532, hsa-miR-4792, hsa-miR-4488, hsa-miR-326, and hsa-miR-7704, wherein said miRNAs are in an isolated form and are not included in a secreted extracellular vesicle or cell.
Determination of the Scope and Content of the Prior Art
(MPEP §2141.01)
Rigoutsos et al. is directed to novel human miRNAs for use in diagnosis, prognosis and therapy of human conditions and diseases. Taught are pharmaceutical compositions comprising a mimic of one or more miRNAs selected form SEQ ID NO: 1 to SEQ ID No: 47972. The composition can comprise engineered transcripts that can sponge various combinations of the miRNAs (paragraph 000177).
Claimed miRNA
SEQ ID NO:
Prior Art Corresponding Seq ID NO
3195
1
38650
1246
2
39237
188-3p
3
47538
16-5p
4
41099
196a-3p
5
45725
32-5p
6
30792
4532
7
38595
4792
8
41354
4488
9
28850
326
10
29569
7704
11
39216
195-5p
12
35851
As set forth above, the sequences claimed in claim 1 of Rigoutsos et al. encompasses all the claimed miRNA. Since the instant claims do not limit the number of miRNA present, the inclusion of all would read on the claims. Furthermore, Rigoutsos et al. teach administering a mimic of one or more (e.g. at least five or more) of the miRNA sequences selected from SEQ ID NO: 1 to 47972 (paragraph 0051; 000177). Delivery systems taught include liposomes (paragraph 000191). In one embodiment, a kit can comprise an oligonucleotide array affixed with a plurality of oligonucleotide probes that interrogate no more than 100 novel miRNAs described herein (including no more than 75 miRNAs, no more than 50 miRNAs, no more than 25 miRNAs, no more than 20 miRNAs, no more than 15 miRNAs, no more than 10 miRNAs, no more than 5 miRNAs or less) (paragraph 000204). Pharmaceutically acceptable carriers taught include buffering agents as well as pH buffered solution (paragraph 000194).
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.02)
While Rigoutsos et al. teaches sequences corresponding to the instant claims, Rigoutsos et al. does not exemplify compositions with the claimed miRNA.
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine any of the miRNA expressly taught into a composition. As taught by Rigoutsos et al. the composition includes mimics of the claimed miRNA which capable of mimicking up to 100% of the activity of the miRNA (paragraph 000177). Thus, based on the teachings of Rigoutsos et al. one skilled in the art would have been motivated to combine miRNA which induce or restore function of the target miRNA. Since the claims encompass more than the expressly recited miRNA, the teachings of Rigoutsos et al. are deemed to render obvious the instantly claimed composition. Regarding claim 20, as set forth above the recitation “consisting essentially of” is interpreted for art purposes as comprising.
Regarding claims 2 and 21, Rigoutsos et al. teaches the amount of miRNA sequence in the sample can be measured or quantified by any known RNA detection methods (paragraph 00039). It is also taught that the amount of an oligonucleotide which can be combined with a carrier material to produce a single dose form will generally be that amount of compound which produces a therapeutic effect (paragraph 000195).The amount of a specific ingredient in a composition is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and reasonably would expect success. The amount of an active ingredient is a parameter that a person of ordinary skill in the art would routinely optimize based on the condition being treated, severity of the condition and desired dosing frequency, among other factors. It would have been obvious to one of ordinary skill in the art at the time of the invention to engage in routine experimentation to determine optimal or workable ranges that produce expected results. Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. In re Aller, 220 F. 2d 454, 105 USPQ 233 (CCPA 1955). NOTE: MPEP 2144.05.
Regarding claims 5-6 and 18, liposome delivery vehicles are suggested.
Regarding claim 10, compositions are taught.
Regarding claims 24-25, buffering agents as pharmaceutically acceptable carriers are taught.
Response to Arguments
Applicants’ arguments filed September 8 2026 have been fully considered but they are not persuasive.
Applicants argue that Rigoutsos provides broad lists of potential miRNAs and generic references to multi-miRNA compositions. However, there is no teaching or suggestion to select the presently claimed 11 miRNAs. The claimed combinations of miRNA are not arbitrary selections from a finite and predictable group of equivalents. They are experimentally identified combination having collective biological effects that could not have been predicted from the mere identification of their individual constituents. Example 1 demonstrates that the claimed miRNA combination is involved in the observed anti-motility and anti-invasive effects. These results are not predictable from the broad disclosure of Rigoutsos. It is argued that before the priority date of the present application, certain miRNAs had been reported as promoting tumor growth, migration, invention, etc. It is argued that the skilled person would have had a reasonable expectation of successfully combining these miRNA to produce anti-tumoral, anti-invasive and pro-apoptotic effects as demonstrated by the present examples.
Regarding Applicant’s arguments, firstly, the examiner noes that claims 22-23 are not included in the rejection above. The prior art does not teach the combination of the claimed 5 miRNA. Thus, while arguments directed to these claims have been considered they do not apply to the claims rejected above. Same with the arguments regarding SEV. These claims are not included in the rejection above.
Regarding the remainder of the arguments, firstly, nothing in the claims limits the scope to only 11 miRNA. Even the consisting essentially of language does not limit the scope of the composition to include only 11 miRNA. Therefore, it is not necessary that the prior art specifically choose the 11 claimed. Regarding the arguments with regards to the particular effect, the claims are not limited to such. Therefore, any effect is not required to be taught by the prior art. None the less Rigoutsos teaches that the activity of SEQ ID NO: 1 to 47972 can be measured and determine whether they are over-expressed or under-expressed. Then administering compositions that mimic one or more miRNAs of SEQ ID No: 1 to 47972. Regarding the arguments with regards to the submitted references and the data in the specification, firstly, MDA-MB-231 cells were utilized which is a highly metastatic triple negative human breast carcinoma cell line and it does not appear any of the references pointed to by Applicants address this cell line. Secondly, there does not appear to be a comparison to other miRNA. Therefore, the examiner cannot agree that the instant specification shows an unexpected effect with the claimed composition commensurate in scope with the claims.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ABIGAIL VANHORN whose telephone number is (571)270-3502. The examiner can normally be reached M-Th 6 am-4 pm EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Neil Hammell can be reached at 571-270-5919. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ABIGAIL VANHORN/ Primary Examiner, Art Unit 1636
