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 of the invention of Group II (methods of treating), and the particular species that are: the compound isoxanthohumol; and AKR1C2 enzymatic substrate, in the reply filed on 04/28/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 1-10 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 without traverse in the reply filed on 04/28/2026.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date as follows.
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed applications, Application Nos. 63/183,313, and 17/734,708, fail to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. The instantly claimed methods require treatment with the particular reagent that is isxanthohumol as well as modulation of AKR1C2, which are elements not provided in the prior filed applications. As such the effective filing date of the instantly claimed methods is the filing date of the instantly application which is 11/21/2023.
Claim Rejections - 35 USC § 112 – Description - New Matter
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.
Claims 16 and 19 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. This is a new matter rejection.
The rejection of the amended and newly presented claims for including subject matter that was not included in the application as originally filed is relevant to several aspects of the claims.
As a first aspect, claim 16 is directed to methods that include “a step for the diagnosis of lipedema that confirmed the tested person is affected by lipedema and an overexpression of AKR1C2 wherein said step comprises the following step: detecting an increment of AKR1C2 enzymatic substrate in a biological sample of a lipedema patient compared to controls”. But the application as originally filed does not contemplate a correlation, as require by the amended claims, between “an overexpression of AKR1C2” and “an increment of AR1C2 enzymatic substrate”. Furthermore, claim 19 sets forth that “the enzymatic substrate is mRNA”. But the application as originally filed does not provide any teaching related to mRNA being a substrate for the enzymatic activity of AKR1C2. For example, the specification teaches (see para 0098 of the publishes application US 20240117436 A1) that the natural substrate of AKR1C2 is Dihydrotestosterone (DHT).
Based on the teachings of the application as originally filed, the claims are considered to encompass new matter.
Claim Rejections - 35 USC § 112 – Failure to Limit
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.
Claim 12 depends form claim 11. Claim 11 specifies a particular compound that is administered or applied in the treatment of lipedema (i.e.: isoxanthohumol). Where claim specifies the inhibitory properties of a compound (e.g.: an inhibitor of AKR1C2 but not AKR1C1), any such properties are dictated by the structure of the compounds; thus where a particular compound is required by claim 11, recitation of the inherent asserted properties of the compound does not further limit the claim.
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 § 112 - Indefiniteness
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 12, 16, 17 and 19 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.
Claim 12 is unclear over recitation of the limitation “the compound is an inhibitor” because there is no antecedent basis for any “compound” in either claim 12 or in claim 11 from which claim 12 depends.
Claims 16 and 19 are unclear over recitation of the limitation “an overexpression of AKR1C2”, as recited in claim 19, because “overexpression” is a relative term, but there is no basis for comparison in either the claims or defined in the specification of the application.
Claims 16 and 19 are unclear over recitation of the limitation “detecting an increment of AKR1C2 enzymatic substrate in a biological sample of a lipedema patient compared to controls” (note that the term “increment” is interpreted using its typical definition as a small increase in a quantity, value, or size). As used in the unclear limitation, the term “increment” is a relative term, but there is no basis for comparison in either the claims or defined in the specification of the application because there is no limitation related to what is used as a control. The limitation is further unclear over recitation of the phrase “a biological sample of a lipedema patient” because the use of the indefinite article “a” in “a lipedema patient” makes it unclear if the step is performed on the same subject that is treated as required in claim 11, or if there is some other patient that is analyzed; this aspect is particularly unclear where the phrase in claim 16 is related to “a … patient”, but the term “patient” is not used in claim 11. This aspect of the claim is further unclear because neither the application as filed, nor the related art, appear to provide for “an increment of AKR1C2 enzymatic substrate” as being indicative of “overexpression of AKR1C2” as apparently required by the limitations of claim 16.
Claims 16 and 19 are unclear over recitation of the limitation “the tested person”, as recited in claim 16 form which claim 19 depends, because there is no antecedent basis for any “tested person”.
Claim 17 is unclear over recitation of the limitation “an AKR1C2 overexpression” because “overexpression” is a relative term, but there is no basis for comparison in either the claims or defined in the specification of the application.
Claim 19 is unclear over recitation of the limitation “the enzymatic substrate is mRNA”, because where the claim depends form claim 16 which requires that an enzymatic substrate of AKR1C2 is detected to confirm an overexpression of AKR1C2, it is unclear how any mRNA is intended to be an enzymatic substrate of AKR1C2.
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, 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.
Claim(s) 11, 12 and 17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Negrao et al (2013) in view of a Al-Ghadban et al (2023).
Relevant to the methods of the rejected claims, Negrao et al teaches the modulation of angiogenesis and inflammation-related proteins in human cells upon application of isoxanthohumol. Negrao et al teaches that isoxanthohumol is a polyphenol with anti-inflammatory, properties which may be of interest for treatment of inflammation-related diseases. Negrao et al specifically teaches that treatment of cells with isoxanthohumol decreases VEGFR2 (e.g.: p.616 - IXN Reduced VEGFR2 Expression and Akt and Erk Downstream Effectors; Fig 7), TNF-a and NF-kB (e.g.: p.615 - IXN Decreased Inflammatory Markers Released by HUVEC and HASMC; Fig 8).
Negrao et al does not explicitly teach the application of isoxanthohumol to the treatment of lipedema, but the role of angiogenesis and inflammation, and the particular makers VEGFR2, TNF-a and NF-kB in lipedema was known in the prior art and is taught by Al-Ghadban et al.
Al-Ghadban et al teaches that lipedema pathology is characterized by increased dilated blood vessels (angiogenesis), inflammation, and fibrosis of the subcutaneous adipose tissue. Al-Ghadban et al uses a model system of human umbilical vein endothelial cells (HUVECs) as an in vitro model for the analysis of lipedema related gene expression, where HUVECs were cultured in conditioned media (CM) collected from healthy (non-lipedema, AQH) and lipedema adipocytes (AQL). Relevant to the limitations of the instantly rejected claims, Al-Ghadban et al teaches that cells treated with conditioned media collected from lipedema adipocytes, there is an increase in expression of VEGFR2 (e.g.: p.3 - Preconditioning of HUVECs with Adipocyte Media Increases the Expression of Angiogenic, Inflammatory, and ECM Markers in 2D Monolayer Culture; Fig 2A) and teaches that increased TNF-a (e.g.: p.2) and NF-kB (e.g.: Fig 5A; p.10) play roles in inflammation.
It would have been prima facie obvious to someone with ordinary skill in the relevant art before the effective filing date of the rejected claims to have tried to treat and/or prevent lipedema in a human subject with the administration of isoxanthohumol. The skilled artisan would have been motivated to try treating lipedema using isoxanthohumol based on the expressed teachings of Negrao et al that isoxanthohumol has anti-inflammatory and antigenic properties and decrease the amount of VEGFR2, TNF-a and NF-kB in cells, and the expressed teachings of Al-Ghadban et al that lipedema pathology includes aspects of angiogenesis and inflammation and includes increased expression of VEGFR2, TNF-a and NF-kB in cells. The skilled artisan would have been further motivated based on the teachings of Al-Ghadban et al that targeting the angiogenic and inflammation markers may represent new treatment opportunities for lipedema, and the teachings of Negrao et al that isoxanthohumol regulates in vivo angiogenesis and inflammatory crosstalk, and is of interest for treatment of inflammation-related diseases. The skilled artisan would have had a reasonable expectation of success because the prior art teaches that isoxanthohumol decreases expression of markers that are increased in the lipedema pathology. With regard to the limitations of claims 11 and 12 that a treatment is “suitable for modulating the activity of AKR1C2” (claim 11) or treatment is an inhibitor of AKR1C2 but not AKR1C1, such elements are inherent with treatment using isoxanthohumol. With regard to the limitations of claim 17, where the claim does not provide any reference of an “overexpression”, the expression level of AKR1C2 in any subject may be considered “overexpression” as compared to a reference with zero expression.
Claim(s) 17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Negrao et al (2013) in view of a Al-Ghadban et al (2023) as applied to claims 11, 12 and 17 above, and further in view of Bertelli et al (US 20220362260 A1; 11/17/2022).
Note that in light of the effective filing date of the claims, US 20220362260 A1 with a publication date of 11/17/2022 is considered prior art.
Negrao et al in view of a Al-Ghadban et al renders obvious the use of isoxanthohumol for the treatment of lipedema.
Negrao et al in view of a Al-Ghadban et al does not specifically address the use of isoxanthohumol contained in an ointment or cream.
However, the use of an ointment or cream for the application of a medication related to lipedeam treatment was known in the prior art and is taught by Bertelli et al (e.g.: para 0028; para 0032; claim 15).
It would have been prima facie obvious to someone with ordinary skill in the relevant art before the effective filing date of the rejected claims to have used a cream or ointment, as taught by Bertelli et al, to provide isoxanthohumol for the treatment of lipedema, as suggested by Negrao et al in view of a Al-Ghadban et al. the skilled artisan would have been motivated to use an ointment or cream based on the expressed teachings of Bertelli et al that an ointment or cream can be a suitable vehicle for delivering a medicaation to a subject for treatment of lipedema.
Conclusion
No claim is allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Żołnierczyk et al (2015) teaches that Isoxanthohumol si a biologically active hop flavonoid with anti-inflammatory and anti- angiogenic effects.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to STEPHEN THOMAS KAPUSHOC whose telephone number is (571)272-3312. The examiner can normally be reached M-F, 8am-5pm.
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Stephen Kapushoc
Primary Examiner
Art Unit 1683
/STEPHEN T KAPUSHOC/Primary Examiner, Art Unit 1683
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