DETAILED ACTION
The examiner of record has changed. Please direct all further correspondence to ZACHARY J MIKNIS whose telephone number is (571) 272-7008.
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 .
Status of the Application
The election and amendment of 27 March 2026 are entered.
Claims 1-20 are pending. Claims 7 and 14 are withdrawn without traverse. Claims 1-6, 8-13, and 15-20 are being examined on the merits.
Election/Restrictions
Applicant’s election of Compound 46 in the reply filed on 27 March 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Claims 7 and 14 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Neither claim recites Compound 46 as elected. Election was made without traverse in the reply filed on 27 March 2026.
Claim Objections
Claim 2 is objected to because of the following informalities: Lys appears twice as an option for residue X3 within Formula II. Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 1-6, 11-13, and 16-20 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of treating sickle cell disease in a subject comprising administering an effective amount of a hepcidin mimetic of SEQ ID NO: 1-46 or pharmaceutical composition thereof, does not reasonably provide enablement for a method for treating sickle cell disease in a subject by administering an effective amount of any hepcidin mimetic or pharmaceutical composition thereof. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
“[T]o be enabling, the specification of a patent must teach those skilled in the art how to make and use the full scope of the claimed invention without ‘undue experimentation.’” Genentech Inc. v. Novo Nordisk 108 F.3d 1361, 1365, 42 USPQ2d 1001, 1004 (Fed. Cir. 1997); In re Wright 999 F.2d 1557, 1561, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993); See also Amgen Inc. v. Chugai Pharm. Co., 927 F.2d 1200, 1212, 18 USPQ2d 1016, 1026 (Fed. Cir. 1991); In re Fisher 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). Further, in In re Wands 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988) the court stated:
Factors to be considered in determining whether a disclosure would require undue experimentation have been summarized by the board in Ex parte Forman [230 USPQ 546, 547 (BdPatAppInt 1986)]. They include (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredict-ability of the art, and (8) the breadth of the claims.
A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557,1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).
Nature of the Invention
The invention is drawn to a method of treating sickle cell disease in a subject comprising administering to the subject an effective amount of a hepcidin mimetic or pharmaceutically acceptable salt thereof, or of a pharmaceutical composition of the hepcidin mimetic or pharmaceutically acceptable salt thereof.
Breadth of the Claims
The claims are broad. Sickle cell disease encompasses a variety of similar yet disparate diseases. The CDC indicates that sickle cell disease includes HbSS, HbSC, HbS beta thalassemia, HbSD, HbSE, HbSO, and HbAS (see e.g. https://www.cdc.gove/sickle-cell/about/index.html). The hepcidin mimetic is claimed at its broadest functionally rather than by any particular structure as in claim 1. Later dependent claims present a genus of compounds R1-X-Y-R2, and at the most specific certain claims recite particular compounds.
State of the Prior Art
The art recognizes that sickle cell diseases are inherited disorders of the red blood cells, causing abnormal hemoglobin production and disrupting normal RBC production and function (see e.g. the above CDC website).
A highly similar compound PTG-300/Rusfertide is known in the prior art as being under investigation for use in polycythemia vera, and differs from Compound 46 by having an N-terminal Asp instead of a Glu residue as instantly claimed (see e.g. Ginzburg et al. Blood 138:390). See also US 2022/0274973 A1 suggesting use of PTG-300 in treatment of β-thalassemia, as well as the PubChem entry for rusfertide (CID 155884410).
Relative Skill of those in the Art
The relative skill of those in the art is high.
Predictability or Unpredictability of the Art
There is a general lack of predictability in the pharmaceutical art. In re Fisher, 427, F. 2d 833, 166, USPQ 18 (CCPA 1970).
Amount of Direction or Guidance Given
The specification offers guidance on hepcidin mimetics that reflects the generic structures claimed as well as the more specific compounds found in certain dependent claims. The specification suggests that hepcidin mimetics might serve to improve CBC parameters including WBC and RBC total counts, hemoglobin levels, hematocrit levels, mean corpuscular volume, mean cell hemoglobin, mean cell hemoglobin concentration, and serum biomarkers (see e.g. p.18). The various sickle cell diseases to be treated include HbSS, HbAC, compound heterozygous sickle-hemoglobin C, HbSD, HbSE, HbSO, HbSβ+ thalassemia, HbSβ-0 thalassemia, HbSS, HbSC, and sickle cell anemia (see e.g. p.18-19).
Presence/Absence of Working Examples
Example 1 concerns synthesis of peptide mimetics via solid-phase synthesis techniques followed by purification, oxidation and or dimerization, and linker activation and conjugation of half-life extension moieties. The example does not indicate what specific peptides were produced via this example.
Example 2 concerns the use of Compound 46 in a mouse model of sickle cell disease. The example demonstrates that Compound 46 when administered in a subcutaneous manner reduces spleen size and liver weight, increases RBC and hemoglobin levels, decreases reticulocytes, increases hematocrit, decreases mean corpuscular volume, increases mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration, increases WBC and lymphocyte counts, increases neutrophil and monocyte counts, and decreases serum total bilirubin and serum lactate dehydrogenase levels.
Quantity of Experimentation Necessary
While SEQ ID NOs:1-45 are not explicitly used in the examples, they are all of sufficiently similar structure and arrangement that one of ordinary skill would find using them in the claimed method to merely be a matter of routine experimentation.
However, claim 1 merely claims a hepcidin mimetic without offering any particular structure required to qualify as a mimetic. The single SEQ ID NO: 46 as used as well as the SEQ ID NOs: 1-45 claimed and disclosed in no way offer a representative number of species for the broadly claimed “hepcidin mimetic”. Even disregarding treatment, the scope of a hepcidin mimetic is such that one of ordinary skill in the art would be posed with an undue burden in preparing sufficient species to enable the entire genus of compounds as claimed.
Furthermore, the generically claimed compound of Formula I being R1-X-Y-R2 is such that a huge number of species result considering the highly generic nature of the X and Y peptides, the options for the R1 moiety, and the ability for any to be optionally PEGylated, have a side chain lipophilic or polymeric moiety substituent, and have an optional disulfide bond. This puts the burden on the skilled artisan to synthesize a huge number of compounds to reasonably represent the genus. While SEQ ID NOs: 1-46 read upon the genus, the variability afforded by Formula I is such that it cannot be reasonably assured that they are representative of the genus as whole.
The specification demonstrates Compound 46/SEQ ID NO: 46 is useful for treatment of sickle cell disease. Since SEQ ID NOs: 1-45 are similar it is reasonable that they are also useful for treatment of sickle cell disease, and as noted above testing of them would merely require routine experimentation. However, even allowing for SEQ ID NOs: 1-45 to be treatments for sickle cell disease does not extend a structure-function nexus between the genus as claimed and the method of treatment. As argued above, the genus is very broad concerning both sickle cell disease and the claimed compound. The skilled artisan is therefore presented with the need to prepare a representative number of species from the broad genus and test those for their ability to treat sickle cell disease. The need to demonstrate a structure-function nexus between Formula (I) and treatment of sickle cell disease rises to the level of undue experimentation given that nearly all efforts on examining the genus is left on the part of the skilled artisan.
Claim 1 further presents an undue burden since the claim is to a compound largely defined by function as a hepcidin mimetic rather than by any particular structure. Claim 1 and its dependent claims not further presenting a structure of a hepcidin mimetic, such as claims 11-13 and 16-18, leave all experimental efforts on the part of the skilled artisan for a genus that encompasses an incalculable number of species. This is further compounded by requiring the skilled artisan to establish a structure-function nexus between the entire genus of hepcidin mimetics and treatment of sickle cell disease. Such efforts rise to the level of undue experimentation.
In view of the Wands factors as discussed above, it is the Examiner’s opinion that the claims are not fully enabled and one of skill in the art would have to engage in undue experimentation to practice the invention as claimed herein, without a reasonable assurance of success.
Double Patenting
A rejection based on double patenting of the “same invention” type finds its support in the language of 35 U.S.C. 101 which states that “whoever invents or discovers any new and useful process... may obtain a patent therefor...” (Emphasis added). Thus, the term “same invention,” in this context, means an invention drawn to identical subject matter. See Miller v. Eagle Mfg. Co., 151 U.S. 186 (1894); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Ockert, 245 F.2d 467, 114 USPQ 330 (CCPA 1957).
A statutory type (35 U.S.C. 101) double patenting rejection can be overcome by canceling or amending the claims that are directed to the same invention so they are no longer coextensive in scope. The filing of a terminal disclaimer cannot overcome a double patenting rejection based upon 35 U.S.C. 101.
Claims 1, 8-13, and 15-20 are provisionally rejected under 35 U.S.C. 101 as claiming the same invention as that of claims 1, 8-13, and 15-20 of copending Application No. 18/872,323 (reference application). This is a provisional statutory double patenting rejection since the claims directed to the same invention have not in fact been patented.
Each of claims 1, 8-13, and 15-20 present identical subject matter as instant claims 1, 8-13, and 15-20. Only minor differences are present in the ordering of compounds in ‘323 as compared to the instant claims, the arrangement of which do not impact the limitations of the ‘323 claims as compared to the instant claims. For instance, SEQ ID NO: 46 is recited first in instant claims 8 and 9 as compared to at the end of claims 8 and 9 of ‘323, but this does not change the claim scope.
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
1. Claims 1-6, 8-10, 15, and 17-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 207, 208, and 218 of copending Application No. 18/016,825 (reference application) and Pradhan et al. (Blood 134:958, published 13 November 2019).
The ‘825 application claims hepcidin analogs, including Compound 101 that matches Compound 46/SEQ ID NO:46 as instantly claimed (see e.g. claim 218). ‘825 also discloses that the compounds can be used in diseases of iron metabolism and dysregulated iron metabolism (see e.g. claims 208 and 208).
The difference between ‘825 and the claimed invention is that ‘825 does not claim a method of treating sickle cell disease with a hepcidin mimetic.
The Pradhan art discloses that sickle cell disease involves dysregulation of hepcidin pathways and suggests hepcidin as a target for therapeutic intervention (see e.g. Abstract).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that the compound and method of ‘825 could have been modified to target hepcidin pathways in sickle cell disease. The rationale comes from ‘825 already indication usage in diseases of iron metabolism and dysregulated iron metabolism, which Prahad shows is the case for patients with sickle cell disease. There would have been a reasonable expectation of success because Prahad suggests targeting of hepcidin for therapy, which ‘825 offers in the form of Compound 101. The invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
With respect to claims 2-6, compound 101 of ‘825 reads upon each genus and sub-genus, also as indicated by the Applicants in electing Compound 46 (see p.19 of the response filed 27 March 2026).
With respect to claims 8-10 and 15, as indicated above Compound 101 of ‘825 reads upon Compound 46/SEQ ID NO: 46 as elected.
With respect to claims 17-20, the clinical parameters as claimed merely reflect known effects of sickle cell disease.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
2. Claims 1-6, 8-13, and 15-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6, 8-13, and 15-20 of copending Application No. 18/872,323 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘323 application claims an overlapping method.
The ‘323 claims a method of treating sickle cell disease by administering a hepcidin mimetic as noted above (see e.g. claim 1). This is identical to instant claim 1.
With respect to claims 2-6, the ‘323 application also claims a compound of Formula I that falls within the genus of instantly claimed Formula I (see e.g. claims 2-6). ‘323 also claims a compound of SEQ ID NO: 46 that reads upon each claim (see e.g. claim 8).
With respect to claims 8-10, as noted above ‘323 claims both identical compounds but also claims SEQ ID NO: 46 (see e.g. claims 8-10).
With respect to claims 11-13, as noted above ‘323 claims identical methods (see e.g. claims 11-13).
With respect to claim 15, as noted above ‘323 claims an identical compound (see e.g. claim 15).
With respect to claims 16-20, as noted above ‘323 claims identical methods (see e.g. claims 16-20).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ZACHARY J MIKNIS whose telephone number is (571)272-7008. The examiner can normally be reached M-F 9-5.
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/ZACHARY J MIKNIS/Patent Examiner, Art Unit 1658
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