DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Claims and Response to Amendments
Claims 1, 3, 5, 6, 10-17, 19-22, 24, 29, 31, 33-35, 37, 38, and 40-45 are pending. Claims 1, 3, 5, 6, 10-17, 19-22, and 24 are withdrawn as explained below. Claims 2, 4, 7-9, 18, 23, 25-28, 30, 32, 36, and 39 are cancelled.
According to 37 CFR 1.145:
"If, after an office action on an application, the applicant presents claims directed to an invention distinct from and independent of the invention previously claimed, the applicant will be required to restrict the claims to the invention previously claimed if the amendment is entered, subject to reconsideration and review as provided in §§ 1.143 and 1.144." See additionally MPEP 821.03.
Amended claims 1, 3, 5, 6, 10-17, 19-22, and 24 are directed to an invention that is independent or distinct from the invention originally claimed for the following reasons:
Claims 1, 3, 5, 6, 10-17, 19-22, and 24 (filed 07/22/2022) examined in the Office Action dated 10/01/2025 were directed toward a bile acid or a pharmaceutically acceptable salt thereof, wherein said bile acid is chenodeoxycholic acid or deoxycholic acid (see Examiner’s note starting on pg. 2 of the Office Action dated 10/01/2025). Claims 1, 3, 5, 6, 10-17, 19-22, and 24 have now been amended in the reply filed on 04/01/2026 such that they are directed toward a method of enabling or enhancing intracellular uptake of a therapeutic compound, comprising administering said therapeutic compound to a human or animal subject with a bile acid chosen from chenodeoxycholic acid or deoxycholic acid, or a pharmaceutically acceptable salt thereof, in conjunction with EDTA, wherein the concentration of the EDTA which is achieved at the surface of the cells into which the intracellular uptake to be enabled or enhanced is from 0.1 mg/mL to 10 mg/mL, and wherein the ratio of the bile acid or salt thereof : therapeutic compound is 100:1 to 1:1 weight-to-weight.
The invention corresponding to claims 1, 3, 5, 6, 10-17, 19-22, and 24 filed on 07/22/2022 and the invention corresponding claims 1, 3, 5, 6, 10-17, 19-22, and 24 filed on 04/01/2026 are related as product and process of use. The inventions can be shown to be distinct if either or both of the following can be shown: (1) the process for using the product as claimed can be practiced with another materially different product or (2) the product as claimed can be used in a materially different process of using that product. See MPEP § 806.05(h). In the instant case, it is known in the prior art that “chenodeoxycholic acid… is a primary bile acid, synthesized in the liver and present in high concentrations in bile that is used therapeutically to dissolve cholesterol gallstones” (see introduction section, 1st sentence of:
LiverTox®: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases;
2012-. Chenodiol (Chenodeoxycholic Acid). [Last updated: 2016 Sep 09]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK547907/
Since applicant has received an action on the merits for the originally presented invention, this
invention has been constructively elected by original presentation for prosecution on the merits.
Accordingly, claims 1, 3, 5, 6, 10-17, 19-22, and 24 are withdrawn from consideration as being directed to a non-elected invention. See 37 CFR 1.142(b) and MPEP § 821.03.
To preserve a right to petition, the reply to this action must distinctly and specifically point out
supposed errors in the restriction requirement. Otherwise, the election shall be treated as a final
election without traverse. Traversal must be timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are subsequently added, applicant must indicate which of the subsequently added claims are readable upon the elected invention.
Should applicant traverse on the ground that the inventions are not patentably distinct,
applicant should submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other invention.
Status of Priority
The present application is a 35 U.S.C. § 371 national stage patent application of International patent application PCT/IB2021/050477, filed on January 22, 2021. This application also claims the benefits of foreign priority to AU2020900183, filed on January 23, 2020.
Specification
The specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Claim Objections
Claims 29, 31, 37, and 44 are objected to because of the following informalities:
For consistency, in claims 29, 31, 37, and 44:
“bile acid or salt” should read“bile acid or salt thereof”
In claim 29, this informality appears twice:
once in item [d] and once in item [f].
In claim 31, this informality appears five times:
Three times in item [c], once in item [d], and once in item [f].
In claim 37, this informality appears once.
In claim 44, this informality appears once.
Appropriate correction is required.
Claims 38 and 45 are objected to under 37 CFR 1.75 as being a substantial duplicate of claims 29 and 31, respectively (see “Claim Rejections - 35 USC § 112(d)” section below for an explanation). When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
------------------------- Rejection Necessitated by Applicant Amendment -------------------------
Claim Rejections - 35 USC § 112(d)
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 38 and 45 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 38 is dependent on claim 29. In other words, claim 38 encompasses all the limitations of claim 29 in addition to the limitation explicitly recited in claim 38. However, the limitation explicitly recited in claim 38 is already encompassed by claim 29. Therefore, claim 38 fails to further limit the subject matter of the claim upon which it depends and is a substantial duplicate of claim 29.
Claim 45 is dependent on claim 31. In other words, claim 45 encompasses all the limitations of claim 31 in addition to the limitation explicitly recited in claim 45. However, the limitation explicitly recited in claim 45 is already encompassed by claim 31. Therefore, claim 45 fails to further limit the subject matter of the claim upon which it depends and is a substantial duplicate of claim 31.
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.
------------------------- Added Rejections -------------------------
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Written Description
Claims 29, 31, 33-35, 37, 38, and 40-45 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
In the instant case, the claims are exceedingly broad. In particular, the claims recite a pharmaceutical composition comprising a bile acid selected from chenodeoxycholic acid, deoxycholic acid, or a pharmaceutically acceptable salt thereof and any therapeutic compound amongst other components. The term “therapeutic compound” encompasses an extremely broad genus of structurally and functionally diverse species, including but not limited to small-molecule drugs, peptides, proteins, oligonucleotides, nucleic acids, plasmids, and other therapeutic compounds.
The specification provides working examples demonstrating cellular uptake of insulin, BSA, casein, and hGH in the presence of bile acid. However, each of these exemplified species is a protein (see last sentence of instant example 13). The specification does not provide examples demonstrating enhanced uptake of small-molecule therapeutic compounds, peptides, oligonucleotides, nucleic acids, plasmids, or other non-protein therapeutic compounds.
According to MPEP § 2163:
“Satisfactory disclosure of a ‘representative number’ depends on whether one of skill in the art would recognize that the inventor was in possession of the necessary common attributes or features possessed by the members of the genus in view of the species disclosed. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See, e.g., Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. Instead, the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are ‘representative of the full variety or scope of the genus,’ or by the establishment of ‘a reasonable structure-function correlation.’ Such correlations may be established ‘by the inventor as described in the specification,’ or they may be ‘known in the art at the time of the filing date.’ See AbbVie, 759 F.3d at 1300-01, 111 USPQ2d 1780, 1790-91 (Fed. Cir. 2014).
The instant specification does not adequately reflect the structural diversity encompassed by the term “therapeutic compound.”
Additionally, the prior art demonstrates that bile-acid-mediated cellular uptake effects are compound-dependent.
Prior art referenced:
Xiao et al. (Xiao) (Xiao, L. et al. Enhanced Liver Targeting of Camptothecin via Conjugation with Deoxycholic Acid. Molecules 2019, 24, 1179.)
For example, the results of Xiao et al. showed that “there was no distinct effect of deoxycholic acid on cellar uptake of CPT [i.e., camptothecin]” (see pg. 4 of 13, 1st paragraph, 2nd to last sentence and Figure 4). Thus, the results of Xiao demonstrate that deoxycholic acid does not uniformly enhance uptake of all therapeutic compounds. Therefore, the art did not recognize a general principle that deoxycholic acid or chenodeoxycholic acid enhances intracellular uptake across the entire therapeutic-compound genus.
Accordingly, because the specification discloses only a limited subset of protein species and fails to provide representative species or common structural characteristics spanning the full breadth of the claimed therapeutic-compound genus, the specification does not reasonably convey possession of the full scope of the claimed invention.
Claims 33-35, 37, 38, and 40-45 , which are dependent on claims 29 or 31, are also rejected for further requiring and/or reciting limitations that do not have written description support (i.e., the “therapeutic compound” limitation).
Applicant can overcome this rejection by amending claims 29 and 31 to recite the following limitation instead:
“a therapeutic compound, wherein said therapeutic compound is a protein”
Note: once claims 29 and 31 are amended, amending claims 35 and 43 to also recite “wherein said therapeutic compound is a protein” would result in claims that are substantial duplicates of claims 29 and 31, respectively.
Conclusion
No claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to KRISTEN ROMERO whose telephone number is (571)272-6478. The examiner can normally be reached M-F 9:30 AM - 6:00 PM ET.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, JEFFREY H. MURRAY can be reached at (571) 272-9023. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KRISTEN W ROMERO/Examiner, Art Unit 1624
/JEFFREY H MURRAY/Supervisory Patent Examiner, Art Unit 1624
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