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 .
DETAILED ACTION
Applicant’s amendments and remarks filed on July 2, 2026 are acknowledged. Claims 3, 4, 17, 18, and 20 have been canceled. Claims 8, 16, 23, and 24 were amended. Claims 1, 2, 5-16, 19, and 21-27 are pending. Claims 1, 2, and 5-7 are withdrawn.
Claims 8-16, 19, and 21-27 are examined on the merits herein.
Priority
This application claims priority to PCT/EP2020/073023 filed on August 17, 2020 which claims priority to DE 10 2019 122 014.9 filed on August 15, 2019.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Withdrawn Objections
In view of Applicant’s amendments and response, the objection to claims 8 and 16 is withdrawn.
Withdrawn Rejections
In view of Applicant’s amendments and response, the 35 U.S.C. 112(d) rejection of claim 20 is withdrawn.
In view of Applicant’s amendments and response, the 35 U.S.C. 112(a) written description rejection is withdrawn.
CLAIM INTERPRETATION
The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The following is a quotation of pre-AIA 35 U.S.C. 112, sixth paragraph:
An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
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. The broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) is limited by the description in the specification when 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is invoked.
As explained in MPEP § 2181, subsection I, claim limitations that meet the following three-prong test will be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph:
(A) the claim limitation uses the term “means” or “step” or a term used as a substitute for “means” that is a generic placeholder (also called a nonce term or a non-structural term having no specific structural meaning) for performing the claimed function;
(B) the term “means” or “step” or the generic placeholder is modified by functional language, typically, but not always linked by the transition word “for” (e.g., “means for”) or another linking word or phrase, such as “configured to” or “so that”; and
(C) the term “means” or “step” or the generic placeholder is not modified by sufficient structure, material, or acts for performing the claimed function.
Use of the word “means” (or “step”) in a claim with functional language creates a rebuttable presumption that the claim limitation is to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites sufficient structure, material, or acts to entirely perform the recited function.
Absence of the word “means” (or “step”) in a claim creates a rebuttable presumption that the claim limitation is not to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is not interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites function without reciting sufficient structure, material or acts to entirely perform the recited function.
Claim limitations in this application that use the word “means” (or “step”) are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action. Conversely, claim limitations in this application that do not use the word “means” (or “step”) are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action.
This application includes one or more claim limitations that use the word “means” or “step” but are nonetheless not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph because the claim limitation(s) recite(s) sufficient structure, materials, or acts to entirely perform the recited function. Such claim limitation(s) is/are: means of an inhibition of the osteoclast differentiation in claim 21.
Claim 21 fails the last prong of the 3-prong analysis because the word “means” recites sufficient structure. Paragraph [0009] of the specification discloses that TLR 7/8 essentially contributes to osteoclast differentiation and thus to bone resorption so that an inhibition of TLR 7/8 can be used for the reduction of bone resorption. Further, TLR 7/8 can be inhibited directly using direct inhibitors such as ODN 2087 or indirectly by inhibiting miR-574-5p. Thus, the specification discloses that the function of osteoclast differentiation is provided by inhibiting miR-574-5p. Claim 21 depends on claim 8 which provides the structure of these inhibitors; therefore, claim 21 includes significant structure capable of performing the function.
Because this/these claim limitation(s) is/are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, it/they is/are not being interpreted to cover only the corresponding structure, material, or acts described in the specification as performing the claimed function, and equivalents thereof.
If applicant intends to have this/these limitation(s) interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, applicant may: (1) amend the claim limitation(s) to remove the structure, materials, or acts that performs the claimed function; or (2) present a sufficient showing that the claim limitation(s) does/do not recite sufficient structure, materials, or acts to perform the claimed function.
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.
Claim 23 is 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.
Claim 23 is indefinite at the recitation of “wherein the RNA analog is completely complementary to miR-574-5p, within the covered portion, but does not cover the whole sequence of miR-574-5p according to SEQ ID NO: 4” because it is unclear what is meant by “within the covered portion” and it is also unclear how the RNA analog can be completely complementary to miR-574-5p and also not cover the whole sequence of miR-574-5p.
Claim 23 recites the limitation "the covered portion". There is insufficient antecedent basis for this limitation in the claim.
Response to Arguments
Applicant's arguments filed July 2, 2026 have been fully considered but they are not persuasive.
Applicant asserts that claim 23 has been amended for clarity to overcome the 35 U.S.C. 112(b) rejection.
This argument is not found persuasive. Claim 23 has been amended to include the limitation “within the covered portion”; however, it is unclear what is meant by this limitation. Further, it is unclear how the RNA analog can be completely complementary to miR-574-5p within the covered portion and also not cover the whole sequence of miR-574-5p.
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 23 and 26 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.
Claim 23 recites the pharmaceutical composition according to claim 16 wherein the RNA analog is completely complementary to miR-574-5p, within the covered portion, but does not cover the whole sequence of miR-574-5p according to SEQ ID NO: 4.
Claim 26 recites the pharmaceutical composition according to claim 16 wherein the RNA analog does not cover the whole sequence of miR-574-5p according to SEQ ID NO: 4.
Claim 16 recites the pharmaceutical composition according to claim 14 wherein the TLR7/8 inhibitor is a single stranded RNA analog which is complementary to miR-574-5p (according to SEQ ID NO: 4). Therefore, claims 23 and 26 do not further limit the claim which it depends on because claim 16 requires the RNA analog to be complementary to miR-574-5p.
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.
Response to Arguments
Applicant's arguments filed July 2, 2026 have been fully considered but they are not persuasive.
Applicant asserts that amended claim 23 further limits the claim over claim 16 and thus overcomes the 35 U.S.C. 112(d) rejection.
This argument is not found persuasive. Claim 23 depends on claim 16 and claim 16 requires the RNA analog to be complementary to miR-574-5p. Therefore, amending claim 23 to add the limitation “within the covered portion” does not further limit the claim which it depends on.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 8, 19, 21, and 27 are rejected under 35 U.S.C. 103 as being unpatentable over Yang et al. (WO 2017/079983; reference cited by Applicant) in view of Gambari et al. (Journal of Cancer Metastasis and Treatment 2019; reference previously cited by the Examiner).
Regarding claim 8, the clause “for the reduction of bone resorption in diseases which are accompanied by an excessive bone resorption” is the preamble and is interpreted as intended use of the invention while the body of the claim sets forth all the limitations. See MPEP 2111.02(II).
Regarding claim 21, the phrase “wherein the bone resorption is reduced by means of an inhibition of the osteoclast differentiation” is interpreted as being covered by miR-574-5p-AntagomiR as recited in claim 8.
Regarding claims 8, 19, 21, and 27, Yang et al. teaches a composition for inhibiting mammalian TLR7 and/or mammalian TLR8 mediated immune responses in cells or a subject containing a miR-574-5p inhibitor, such as an antagomiR-574-5p, and/or pharmaceutically acceptable excipients [page 5, second full paragraph; paragraph bridging pages 16-17]. Yang et al. also teaches that miR-574-5p inhibitors are useful in applications related to TLR7 and/or TLR8 mediated immune and inflammatory responses and thus are capable of treating or preventing conditions involving unwanted immune activity such as autoimmune diseases [page 4, second full paragraph] wherein autoimmune diseases includes rheumatoid arthritis [page 20, fourth full paragraph].
However, Yang et al. does not teach that the miR-574-5p-AntagomiR is a peptide nucleic acid (PNA).
Gambari et al. teaches that among biomolecules proposed in anti-miRNA therapy, peptide nucleic acids (PNAs) are appealing, in consideration of their stability and efficacy in recognizing RNA targets. PNAs against tumor associated miRNAs have proven to be efficient in inducing anti-tumor effects both in vitro and in vivo [abstract].
It would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the antagomiR-574-5p of Yang et al. as a peptide nucleic acid as taught by Gambari et al. One of skill in the art would have been motivated to do so because Gambari et al. taught that PNAs are appealing because of their stability and efficacy in recognizing RNA targets.
Claims 9-13 are rejected under 35 U.S.C. 103 as being unpatentable over Yang et al. (WO 2017/079983; reference cited by Applicant) in view of Gambari et al. (Journal of Cancer Metastasis and Treatment 2019; reference previously cited by the Examiner) as applied to claims 8, 19, 21, and 27 above, and further in view of Vangijzegem et al. (Expert Opinion on Drug Delivery 2019; reference previously cited by the Examiner).
Regarding claims 9-13, the teachings of Yang et al. and Gambari et al. are discussed above.
However, Yang et al. and Gambari et al. do not teach a pharmaceutical
composition comprising carriers such as nanocarriers wherein the nanocarriers are nanoparticles like iron oxide nanoparticles. Yang et al. and Gambari et al. also do not teach covalently binding the inhibitor to the carrier.
Vangijzegem et al. teaches that bounding or loading drugs onto iron oxide nanocarriers can improve the therapeutic effect of drugs due to the magnetic and biological properties of the nanoparticles. Further, poor solubility, high toxicity, nonspecific delivery and short circulating half-lives can be overcome by conjugating drugs to iron oxide nanoparticles [page 69, right column, first full paragraph]. Vangijzegem et al. teaches that drugs loaded onto the nanoparticles can be efficiently guided and selectively delivered toward targeted locations [abstract]. In addition, Vangijzegem et al. teaches that biomedical applications require sizes (inorganic core) below 100 nm as well as narrow size distributions [page 70, left column, first paragraph]. Vangijzegem et al. also teaches that peptides used as vectors to target two overexpressed cell proteins on prostate cancer cells were conjugated onto iron oxide nanoparticles through formation of amide bonds with polymer coated iron oxide nanoparticles [page 73, right column, first paragraph].
It would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the composition of Yang et al. and Gambari et al. wherein the composition contains iron oxide nanoparticles as taught by Vangijzegem et al. One of skill in the art would have been motivated to do so in order to achieve the predictable result of targeted drug delivery and improved therapeutic effect of the pharmaceutical composition as taught by Vangijzegem et al.
Claims 14-16, 23, and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Yang et al. (WO 2017/079983; reference cited by Applicant) in view of Gambari et al. (Journal of Cancer Metastasis and Treatment 2019; reference previously cited by the Examiner) as applied to claims 8, 19, 21, and 27 above, and further in view of Wimley et al. (WO 2019/084343; reference cited by Applicant).
Regarding claims 14-16, 23, and 25, the teachings of Yang et al. and Gambari et al. are discussed above. Yang et al. also teaches the use of miR-574-5p inhibitors as antagonists for mammalian TLR7 and/or mammalian TLR8 wherein the miR-574-5p inhibitors can be single-stranded RNA complementary to miR-574-5p [page 5, last two paragraphs].
However, Yang et al. and Gambari et al. do not teach cell penetrating peptides or a PEG linker.
Wimley et al. teaches that the term “therapeutically effective amount” refers to an amount (e.g., a pharmaceutical dose of a composition containing a CPP) effective in inducing a desired biological effect [page 12, last paragraph]. Wimley et al. also teaches that a linker refers to a linkage between two elements. A linker can be a covalent bond and can be a molecule used to couple a cell penetrating peptide to a compound. Further, a linker also refers to a moiety (e.g., a PEG polymer) [page 10, last paragraph bridging to page 11]. Wimley et al. also identified cell penetrating peptides that can deliver cargo to intracellular compartments [page 19, first paragraph].
It would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to covalently link a cell penetrating peptide as taught by Wimley et al. to the inhibitor in the pharmaceutical composition of Yang et al. and Gambari et al. One of skill in the art would have been motivated to do so in order to achieve the predictable result of delivering cargo to intracellular compartments as taught by Wimley et al.
Claim 22 is rejected under 35 U.S.C. 103 as being unpatentable over Yang et al. (WO 2017/079983; reference cited by Applicant) in view of Gambari et al. (Journal of Cancer Metastasis and Treatment 2019; reference previously cited by the Examiner) as applied to claims 8, 19, 21, and 27 above, and further in view of Zanardi et al. (Artificial DNA: PNA & XNA 2012; reference previously cited by the Examiner).
Regarding claim 22, the teachings of Yang et al. and Gambari et al. are discussed above.
However, Yang et al. and Gambari et al. do not teach that the miR-574-5p-AntagomiR is bound to lysine or a modified lysine.
Zanardi et al. teaches that insertion of one or more lysine residues as a tail into a PNA backbone gives some beneficial effects, for example on the solubility in aqueous solutions [page 81, left column bridging to right column].
It would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the composition of Yang et al. and Gambari et al. wherein the miR-574-5p-AntagomiR is bound to lysine because Yang et al. taught a miR-574-5p-AntagomiR, Gambari et al. taught that PNAs are appealing because of their stability and efficacy in recognizing RNA targets, and Zanardi et al. taught inserting lysine residues as a tail into a PNA backbone. One of skill in the art would have been motivated to do so in order to achieve the predictable result of solubility of the PNA in aqueous solutions as taught by Zanardi et al.
Response to Arguments
Applicant's arguments filed July 2, 2026 have been fully considered but they are not persuasive.
Applicant asserts the following:
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These arguments are not found persuasive. The Declaration previously submitted by the Applicant compared the results of LNA-SPION with the CPP-PNA AntagomiR construct. The comparison is not appropriate because the same delivery vehicles were not used in the comparison and Applicant’s experiments do not control for this variable. Specifically, a comparison should have been made with a CPP formulation not a SPION formulation. Thus, contrary to Applicant's assertions, the declaration does not compare the results obtained from the claimed invention with the closest prior art. With respect to Applicant’s arguments regarding the Gambari et al. reference, Gambari et al. does not need to teach or suggest that PNA would be superior to LNA or that LNA should be replaced by PNA. A teaching, suggestion, or motivation is not the only rationale that may be used to support a conclusion of obviousness. Based on the teachings of Gambari et al., one of ordinary skill in the art would have had a reasonable expectation of success in modifying the antagomiR-574-5p of Yang et al. as a peptide nucleic acid because Gambari et al. taught that PNAs are appealing because of their stability and efficacy in recognizing RNA targets and it would have amounted to a simple substitution of one known element for another to obtain predictable results. Furthermore, based on the teachings of Gambari et al., Applicant’s observations are not surprising or unexpected.
Applicant also asserts that claim 23 is not taught or suggested by the prior art as Bateman et al. does not suggest an inhibitor that covers only a portion of SEQ ID NO: 4.
This argument is not found persuasive. Claim 23 was previously rejected and stands rejected over Yang et al. in view of Gambari et al. and further in view of Wimley et al. It is noted that Bateman et al. was previously used in combination with Yang et al. and Gambari et al. to render obvious claim 24, not claim 23.
Allowable Subject Matter
Claim 24 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
No claims are allowed.
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 CHRISTINA TRAN whose telephone number is (571)270-0550. The examiner can normally be reached M-F 7:30 - 5:00pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jennifer Dunston can be reached at (571) 272-2916. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/C.T./
Examiner, Art Unit 1637
/Jennifer Dunston/Supervisory Patent Examiner, Art Unit 1637
Prosecution Insights