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 .
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 08/27/2025 has been entered.
Election/Restrictions
Applicant’s election without traverse of DHX and pulmonary fibrosis in the reply filed on 2/24/2025 is acknowledged.
Applicants elected DHX as a Gas protein coupled receptor agonist, and pulmonary fibrosis as the species of indication.
Claims 1-2, 4 and 10-12 read on the elected species.
Claims 5-9 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 12/31/2024.
Current Status of 18/422,541
The amended claims of 8/27/2025 were used in this Office Action.
Claims 1-2, 4 and 10-12 are examined on the merits.
Priority
This application is a divisional of now abandoned application 17/934,009, which claims priority to abandoned application 16/965,122, which was a national stage entry of PCT/US2019/016178, which claims priority to US provisional application 62/624,535, filed 1/31/2018.
The instant claims find support from the provisional. Therefore, the effective filing date is 1/31/2018.
Information Disclosure Statement
The information disclosure statement (IDS), submitted on 7/21/2025, is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Response to Arguments
Applicants’ claim amendments and Remarks of 8/27/2025 are acknowledged and have been considered.
Any rejection and/or objection not specifically addressed or modified below is herein withdrawn.
In regard to the 103 rejection, this rejection is withdrawn. Applicants remarks with Examiner’s answer is summarized below:
Applicants submit that claim 1 as amended so that the agonist administered is specific for DRD1 expressed preferentially in the mesenchymal cell. Oncoceutics mentions dopamine receptors D1, D2, D3, D4, or D5 but does not identify any one of them as being selective for any agonist.
This point is not persuasive. Any agonist of claim 4 inherently teaches due to claim construction that the agonist of claim 4 is specific and selective for DRD1 per Applicants’ claim construction.
Applicants submit that MIRONES does not appear to teach that Gas protein coupled receptor is preferentially expressed in mesenchymal cells as compared to epithelial or endothelial cells.
After a review of MIRONES, Examiner agrees and withdraws this 103.
Applicants point out that MIRONES says that SKF-38393, a D1R-class agonist had no effects on hMPCs migration.
Although interesting, SKF-38393 is not commensurate with the scope of the current 103.
Applicants submit that the claimed method requires a Gas protein coupled receptor agonist that is (a) specific for DRD1 expressed preferentially in mesenchymal cells; (b) selective to D1 dopamine receptor as compared to D2, D3, D4, or D5 dopamine receptor and (c) effective in treating a fibrotic pathology.
Examiner understands what claim 1 now recites. Parts (a) and (b) are addressed above in the first bullet point’s response.
Applicants submit, in regard to the advisory action, that the DHX compound is a known DRD1 agonist and thus does not need to be further limited.
Examiner clarifies that other Gas protein coupled receptors (other than DHX) still need to be searched.
Response to Amendment
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.
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 1, 4, and 10 are rejected under 35 U.S.C. 103 as being unpatentable over: ONCOCEUTICS (WO 2017/132661 A2, seen in IDS of 1/3/2025), as evidenced by MAISON (Maison et al., “Dopaminergic Signaling in the Cochlea: Receptor Expression Patterns and Deletion Phenotypes”, Journal Of Neuroscience, January 4, 2012), and in view of CHAKROBORTY (Charkroborty et al., “Activation of Dopamine D1 Receptors in Dermal Fibroblasts Restores Vascular Endothelial Growth Factor A Production by these cells and subsequent angiogenesis in Diabetic Cutaneous Wound Tissues”, Elsevier, September 2016) and NICHOLS (WO 02056875A2).
ONCOCEUTICS teaches treating or preventing pulmonary fibrosis, idiopathic pulmonary fibrosis (paragraph [00303]) by administering a therapeutically effective amount of an agonist that targets at least one dopamine receptor or G protein-coupled receptor (GPCR) (paragraph [0018]), or a pharmaceutically acceptable salt thereof (paragraph [0008]), which help teach the limitations of claim 1.
ONCOCEUTICS teaches the dopamine receptor (DR) can be DRD1 (paragraph [00136]).
ONCOCEUTICS is silent to Gas protein coupled receptor is preferentially expressed in mesenchymal cells as compared to endothelial cells. ONCOCEUTICS does not teach the elected species of agonist.
MAISON is relied upon for the beneficial teaching that the dopamine receptor family includes five G-protein-coupled subtypes, from two major classes: D1 and D5 are coupled to the Gαs-protein; D2, D3, and D4 are coupled to the Gαi-protein (Left col. Page 345).
CHAKROBORTY teaches that DRD1 is present and functional in fibroblasts (figure 4A) and shows that D1 agonist do not affect endothelial cells in vitro (figure 3’s description). This teaches that Dopamine D1 (a type of Gas protein coupled receptor) is preferentially expressed in mesenchymal cells as compared to endothelial cells (i.e. not present in endothelial cells). This teaches a limitation of claim 1.
None of the references above teach dihydrexidine.
NICHOLS teaches dihydrexidine (the elected species of Gas protein coupled receptor agonist) as a selective D1 dopamine agonist, as compared to D2, D3, D4, or D5 dopamine receptor (reference claims 1-2 and page 9).
Any agonist of claim 4 inherently teaches due to claim construction that the agonist of claim 4 is specific and selective for DRD1 per Applicants’ claim construction. This teaches claim 4.
ONCOCEUTICS teaches a method of treating or preventing pulmonary fibrosis or idiopathic pulmonary fibrosis (paragraph [00303] and [0018]) by administering a therapeutically effective amount of an agonist that targets at least one dopamine receptor or G protein-coupled receptor (GPCR) (paragraph [0018]) including a DRD1 (paragraph [00136]), or a pharmaceutically acceptable salt thereof (paragraph [0008]).
Regarding claim 1’s “wherein” clauses, MPEP 2111.04 states, a “‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’” Id. (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)).
In this case, the wherein clause expresses the desired result of the positive step of administering a Gas protein coupled receptor agonist as a treatment for a subject with fibrosis. Since the prior art reference teaches the instantly claimed method, this limitation is met. See also MPEP 2112.02. This teaches claims 1 and 10.
In addition to the paragraphs above, CHAKROBORTY seems to suggest that DRD1 is present and functional in fibroblasts (figure 4A) and shows that D1 agonist do not affect endothelial cells in vitro (figure 3’s description). This teaches that Dopamine D1 (a type of Gas protein coupled receptor as evidenced by MAISON) is preferentially expressed in mesenchymal cells as compared to endothelial cells (i.e. not present in endothelial cells).
Applicants are reminded that the office does not have the facilities and resources to provide the factual evidence needed in order to establish that the product of the prior art does not possess the same material, structural and functional characteristics of the claimed product. In the absence of evidence to the contrary, the burden is on the applicant to prove that the claimed product is different from those taught by the prior art and to establish patentable differences. See In re Best 562F.2d 1252, 195 USPQ 430 (CCPA 1977) and Ex parte Gray 10 USPQ 2d 1922 (PTO Bd. Pat. App. & Int. 1989).
The artisan would find obvious before the effective filing date of the claimed invention to substitute Applicants’ elected dihydrexidine, a known dopamine agonist (NICHOLS page 9 and claims 1-2), for the dopamine agonist taught in ONCOCEUTICS. The artisan would be motivated to substitute NICHOLS’s dopamine agonist, dihydrexidine, to replace dopamine agonist taught in ONCOCEUTICS thereby arriving at the instant invention. The artisan would expect that substituting NICHOLS’s dopamine agonist in place of the dopamine agonist used in ONCOCEUTICS would yield predictable results since the prior art references NICHOLS and ONCOCEUTICS each teach equivalents (dopamine agonists). MPEP 2144.06(II). Therefore, dihydrexidine dopamine agonist would be expected to behave in the same way as the replaced ONCOCEUTICS dopamine agonist (ie., to treat various claimed fibrotic pathologies, as discussed, above, per ONCOCEUTICS) since each are known dopamine agonists. This teaches claim 4.
There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the time of invention, but only that the subject matter is in fact inherent in the prior art reference. Chemical properties are inherent to their compounds. Products of identical chemical composition can not have mutually exclusive properties. A chemical composition, dihydrexidine, and its properties, specific for DRD1 expressed preferentially in the mesenchymal cell and selective to D1 dopamine receptor, are inseparable. See MPEP 2112.01 (II).
Claims 1-2, 4 and 10-12 are rejected under 35 U.S.C. 103 as being unpatentable over: ONCOCEUTICS (WO 2017/132661 A2, seen in IDS of 1/3/2025), as evidenced by MAISON (Maison et al., “Dopaminergic Signaling in the Cochlea: Receptor Expression Patterns and Deletion Phenotypes”, Journal Of Neuroscience, January 4, 2012), and in view of CHAKROBORTY (Charkroborty et al., “Activation of Dopamine D1 Receptors in Dermal Fibroblasts Restores Vascular Endothelial Growth Factor A Production by these cells and subsequent angiogenesis in Diabetic Cutaneous Wound Tissues”, Elsevier, September 2016) and NICHOLS (WO 02056875A2), and KORDES (Kordes, Claus, et al. “Stellate cells are mesenchymal stem cells”, European Journal of Medical Research, (2014), Vol. 19, Suppl. 1: S6, pp. 1-2), COHEN (Cohen, Rachel. “Dopamine and Chronic Pain”, South West Spine and Pain Center, May 13, 2015, Accessed 10 Mar 2022. Available from: < https://www.southwestspineandpain.com/blog/dopamine-and-chronic-pain > ), and in view of: PULMONARYFIBROSISNEWS (“Pain and IPF: What’s the deal”, Pulmonary Fibrosis News, November 13, 2017. Accessed 17 March 2022. Available from < https://www.pulmonaryfibrosisnews.com/2017/11/13/ipf-pain-what-is-going-on-how-to-alleviate-it/ > ).
Claims 1, 4, and 10 are taught above.
ONCOCEUTICS does not teach the specific types of mesenchymal cell.
MIRONES teaches a mesenchymal cell as a fibroblast (page 2531, right column third paragraph), which teaches claim 2.
KORDES teaches that stellate cells are a type of mesenchymal cells (page 1 background).
None of the references above or in the first obviousness rejection teach administering an additional agent of dopamine.
COHEN teaches that dopamine systems in the brain are also involved in the central regulation of chronic pain (page 1).
PULMONARYFIBROSISNEWS teaches that idiopathic pulmonary fibrosis (IPF) can be a painful disease, and can present with lower back pain that shoots down into the legs. This pain is thought to be from the swelling and fluid retention from IPF and due to the tight chest and back muscles from persistent coughing from IPF (pages 1-3). This helps teach claims 11-12.
ONCOCEUTICS’s method also be expected to affect the fibroblast and stellate mesenchymal cells (therefore rejects claims 1-3 and 10) since fibroblasts (MIRONES page 2531, right column third paragraph) and stellate cells (KORDES page 1) are sub-types of mesenchymal cells. This teaches claim 2.
The artisan would find obvious before the effective filing date of the claimed invention to add an additional therapeutic agent of dopamine. Since COHEN teaches dopamine is a known pain-killer and known to regulate chronic pain (page 1), that the artisan would be motivated to add it as an adjuvant to dihydrexidine to treat fibrosis. The artisan would expect that the pain-killer dopamine would add to/adjuvant the treatment with dihydrexidine of the fibrotic pathologies, many of which are very painful (PULMONARYFIBROSISNEWS pages 1-3). This teaches claims 11-12.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GILLIAN A HUTTER whose telephone number is (571)272-6323. The examiner can normally be reached M-F 7:30-5.
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/G.A.H./Examiner, Art Unit 1625 /Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625