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 .
Claims 1-20 are pending.
Election/Restrictions
Applicant's election with traverse of Group I in the reply filed on August 4,2025 is acknowledged. Applicant's election with traverse of the species nucleic acid as the inhibitor in the reply filed on August 4, 2025 is acknowledged. The traversal is on the ground(s) that examining would not place an undue burden on the Examiner. This is not found persuasive because the inventions have acquired a separate status in the art in view of their different classification, the inventions require a different field of search the prior art applicable to one invention would not likely be applicable to another invention (art on the product would likely not be applicable to the method of treating sickle cell anemia and methods using anti-PUM1 antibodies would not be applicable for methods of genome editing) and the inventions are likely to raise different non-prior art issues under 35 U.S.C. 101 and/or 35 U.S.C. 112, first paragraph. In addition, as disclosed in the Restriction, If the elected species is found to be allowable, the search will be expanded by the Examiner to consider additional species and subgenuses within the genus.
Claims 5-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected inventions, there being no allowable generic or linking claim. Claims 2 and 4 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species.
Applicant's election with traverse of Group I in the reply filed on August 4,2025 is acknowledged.
Claims 1 and 3 are under examination.
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.
Claims 1 and 3 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The claims are drawn to a method of treating sickle cell anemia or beta-thalassmia, comprising administering to a patient a composition comprising an effective amount of an inhibitor of Pumilio-1 (PUM1) wherein the inhibitor is a nucleic acid.
The specification discloses that HBG1 mRNA levels were stabilized when PUM1 is knocked down, suggesting that PUM1 plays an erythroid specific role in the degradation of HBG1 mRNA (paragraph 50). The specification disclose that there was a specific increase in the HBG1 mRNA levels in polyribosomal fractions of PUM1 knocked down HUDEP2 cells suggesting that HBG1 mRNA is more actively translated under the conditions of reduced PUM1 levels (Id). The specification discloses that the results demonstrate that PUM1 regulates HBG1 both at the level of mRNA stability and translation. PUM 1 expression increases during erythroid differentiation indicating that PUM1 serves as a post-transcriptional regulator of y-globin in adult human erythroid cells (Id). The specification discloses that elevated fetal hemoglobin levels was observed in a patient harboring a heterozygous PUM1 mutation with more than 10-fold increase over the healthy parent's level (paragraph 52).
The specification disclose that a "nucleic acid" can be RNA or DNA, and can be single or double stranded, and can be selected, for example, from a group including: nucleic acid encoding a protein of interest, oligonucleotides, nucleic acid analogues, for
example peptide-nucleic acid (PNA), pseudo-complementary PNA (pc-PNA), locked
nucleic acid (LNA) etc. Such nucleic acid sequences include, for example, but are not
limited to, nucleic acid sequence encoding proteins, for example that act as
transcriptional repressors, molecules, ribozymes, small inhibitory nucleic acid
sequences, for example but are not limited to RNAi, shRNAi, siRNA, micro RNAi
(mRNAi), antisense oligonucleotides etc. (paragraph 40)
Persaud et al (Expert Opinion Emerging Drugs 29: 327-346, 2024) discloses that allogeneic hematopoietic stem cell transplantation (HSCT) from a human leukocyte antigen (HLA) matched sibling is the only established curative intervention for sickle cell disease (page 339, 2nd column, 5th paragraph). Persaud disclose that there have been significant advances in our understanding of the pathophysiology of sickle cell disease but therapeutic options remain limited (page 341, 1st column, 3rd paragraph).
Khan et al ( Expert Opinion Drug Delivery 20:1167-1187, 2023) discloses that the applicability of siRNA therapeutics is very challenging due to various pathophysiological barriers that hamper its target reach, which is the cytosol, and execution of gene silencing action (Abstract).
One cannot extrapolate the teaching of the specification to the enablement of the claims because the specification does not provide examples or guidance for treating either sickle cell anemia or beta-thalassmia with an siRNA to PUM1. The specification discloses that HBG1 mRNA levels were stabilized when PUM1 is knocked down, suggesting that PUM1 plays an erythroid specific role in the degradation of HBG1 mRNA. The specification discloses that elevated fetal hemoglobin levels was observed in a patient harboring a heterozygous PUM1 mutation with more than 10-fold increase over the healthy parent's level. There is no examples demonstrating any siRNA was capable of treating either sickle cell anemia or beta-thalassmia. The specification does not provide a nexus between the administration of siRNA to PUM1 and the treatment of sickle cell anemia or beta-thalassmia.
MPEP 2164.03 states that
The amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). The “amount of guidance or direction” refers to that information in the application, as originally filed, that teaches exactly how to make or use the invention.
MPEP 2164.03 further states that
The “predictability or lack thereof” in the art refers to the ability of one skilled in the art to extrapolate the disclosed or known results to the claimed invention. If one skilled in the art can readily anticipate the effect of a change within the subject matter to which the claimed invention pertains, then there is predictability in the art. On the other hand, if one skilled in the art cannot readily anticipate the effect of a change within the subject matter to which that claimed invention pertains, then there is lack of predictability in the art. Accordingly, what is known in the art provides evidence as to the question of predictability. …
The scope of the required enablement varies inversely with the degree of predictability involved, but even in unpredictable arts, a disclosure of every operable species is not required. A single embodiment may provide broad enablement in cases involving predictable factors, such as mechanical or electrical elements. In re Vickers, 141 F.2d 522, 526-27, 61 USPQ 122, 127 (CCPA 1944); In re Cook, 439 F.2d 730, 734, 169 USPQ 298, 301 (CCPA 1971). However, in applications directed to inventions in arts where the results are unpredictable, the disclosure of a single species usually does not provide an adequate basis to support generic claims. In re Soll, 97 F.2d 623, 624, 38 USPQ 189, 191 (CCPA 1938). In cases involving unpredictable factors, such as most chemical reactions and physiological activity, more may be required. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970) (contrasting mechanical and electrical elements with chemical reactions and physiological activity). See also In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993); In re Vaeck, 947 F.2d 488, 496, 20 USPQ2d 1438, 1445 (Fed. Cir. 1991). This is because it is not obvious from the disclosure of one species, what other species will work.
MPEP 2164.08(b) states that
The presence of inoperative embodiments within the scope of a claim does not necessarily render a claim nonenabled. The standard is whether a skilled person could determine which embodiments that were conceived, but not yet made, would be inoperative or operative with expenditure of no more effort than is normally required in the art. Atlas Powder Co. v. E.I. du Pont de Nemours & Co., 750 F.2d 1569, 1577, 224 USPQ 409, 414 (Fed. Cir. 1984) (prophetic examples do not make the disclosure nonenabling).
Although, typically, inoperative embodiments are excluded by language in a claim (e.g., preamble), the scope of the claim may still not be enabled where undue experimentation is involved in determining those embodiments that are operable. A disclosure of a large number of operable embodiments and the identification of a single inoperative embodiment did not render a claim broader than the enabled scope because undue experimentation was not involved in determining those embodiments that were operable. In re Angstadt, 537 F.2d 498, 502-503, 190 USPQ 214, 218 (CCPA 1976). However, claims reading on significant numbers of inoperative embodiments would render claims nonenabled when the specification does not clearly identify the operative embodiments and undue experimentation is involved in determining those that are operative.
Given the disclosure of the specification and the teaching in the art that indicates the unpredictability of treating either sickle cell anemia or beta-thalassmia, one skilled in the art could not predictably either sickle cell anemia or beta-thalassmia with a PUM1 siRNA.
The specification discloses that HBG1 mRNA levels were stabilized when PUM1 is knocked down, suggesting that PUM1 plays an erythroid specific role in the degradation of HBG1 mRNA (paragraph 50). The specification discloses that there was a specific increase in the HBG1 mRNA levels in polyribosomal fractions of PUM1 knocked down HUDEP2 cells suggesting that HBG1 mRNA is more actively translated under the conditions of reduced PUM1 levels (Id). The specification discloses that the results demonstrate that PUM1 regulates HBG1 both at the level of mRNA stability and translation. PUM 1 expression increases during erythroid differentiation indicating that PUM1 serves as a post-transcriptional regulator of y-globin in adult human erythroid cells (Id). The specification discloses that elevated fetal hemoglobin levels was observed in a patient harboring a heterozygous PUM1 mutation with more than 10-fold increase over the healthy parent's level. However, the specification does not disclose any example of using PUM1 siRNA to treat either sickle cell anemia or beta-thalassmia.
Therefore, in view of the breadth of the claims, lack of guidance in the specification, the absence of working examples, and the state of the art, it would require undue experimentation for one skilled in the art to practice the invention as broadly claimed.
Claims 1 and 3 are rejected under 35 U.S.C. 112(a), 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claims are drawn to a method of treating sickle cell anemia or beta-thalassmia, comprising administering to a patient a composition comprising an effective amount of an inhibitor of Pumilio-1 (PUM1).
The specification discloses that HBG1 mRNA levels were stabilized when PUM1 is knocked down, suggesting that PUM1 plays an erythroid specific role in the degradation of HBG1 mRNA (paragraph 50).
The specification discloses that the PUM1 inhibitor can be an antibody (paragraph 58) but does not provide any specific anti-PUM1 antibodies nor any examples of using an anti-PUM1 antibody to treat sickle cell anemia or beta-thalassmia.
The specification discloses that the PUM1 inhibitor can be an siRNA (paragraph 40) but does not provide any specific siRNAs to treat sickle cell anemia or beta-thalassmia
The specification disclose that the term "small molecule" refers to a chemical agent including, but not limited to, peptides, peptidomimetics, amino acids, amino acid
analogs, polynucleotides, polynucleotide analogs, aptamers, nucleotides, nucleotide
analogs, organic or inorganic compounds (i.e., including heteroorganic and
organometallic compounds) having a molecular weight less than about 10,000 grams
per mole, organic or inorganic compounds having a molecular weight less than about
5,000 grams per mole, organic or inorganic compounds having a molecular weight less than about 1,000 grams per mole, organic or inorganic compounds having a molecular
weight less than about 500 grams per mole, and salts, esters, and other
pharmaceutically acceptable forms of such compounds (paragraph 39). However, the specification does not disclose any examples of small molecules that inhibit PUM1 and are capable of treating sickle cell anemia or beta-thalassmia.
The specification does not provide adequate written description of the claimed genus of PUM1 inhibitors. The legal standard for sufficiency of a patent's (or a specification's) written description is whether that description "reasonably conveys to the artisan that the inventor had possession at that time of the. . .claimed subject matter", Vas-Cath, Inc. V. Mahurkar, 19 USPQ2d 1111 (Fed. Cir. 1991). In the instant case, the specification does not convey to the artisan that the Applicant had possession at the time of invention the genus of PUM1 inhibitors that are capable of treating sickle cell anemia or beta-thalassmia.
The guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, § 1 "Written Description" Requirement make clear that if a claimed genus does not show actual reduction to practice for a representative number of species, then the Requirement may be alternatively met by reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the Applicant was in possession of the genus (Federal Register, Vol. 66, No. 4, pages 1099-1111, Fri. January 5, 2001, see especially page 1106 column 3).
The specification does not provide adequate written description of the claimed invention. The legal standard for sufficiency of a patent's (or a specification's) written description is whether that description "reasonably conveys to the artisan that the inventor had possession at that time of the. . .claimed subject matter", Vas-Cath, Inc. V. Mahurkar, 19 USPQ2d 1111 (Fed. Cir. 1991). In the instant case, the specification does not convey to the artisan that the Applicant had possession at the time of invention of the claimed invention, the genus of PUM1 inhibitors that are capable of treating sickle cell anemia or beta-thalassmia. The genus of PUM1 inhibitors are claimed by function, the ability to treat sickle cell anemia or beta-thalassmia. The specification does not disclose any small molecules, siRNA nor antibodies that are capable of these functions. The Federal Circuit addressed the application of the written description requirement to DNA-related inventions in University of California v. Eli Lilly and Co., 119 F.3d 1559, 43 USPQ2d 1398 (Fed. Cir. 1997). The court stated that “[a] written description of an invention involving a chemical genus, like a description of a chemical species, requires a precise definition, such as by structure, formula, [or] chemical name, of the claimed subject matter sufficient to distinguish it from other materials.” Id. At 1567, 43 USPQ2d at 1405. The court concluded that “naming a type of material generally known to exist, in the absence of knowledge as to what that material consists of, is not a description of that material.” Id.
The Federal Circuit clarified that a molecule can be adequately described without disclosing its complete structure. See Enzo Biochem, Inc. V. Gen-Probe Inc., 296 F.3d 1316, 63 USPQ2d 1609 (Fed. Cir. 2002). The Enzo court adopted the standard that the written description requirement can be met by “show[ing] that an invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics ....i.e., complete or partial structure, other physical and/or chemical properties, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics. “ Id. At 1324, 63 USPQ2d at 1613 (emphasis omitted, bracketed material in original).
However, without a correlation between structure and function, the claim does little more than define the claimed invention by function. That is not sufficient to satisfy the written description requirement. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406 (“definition by function … does not suffice to define the genus because it is only an indication of what the gene does, rather than what it is”).
Thus, the instant specification may provide an adequate written description of the genus of PUM1 inhibitors that are capable of treating sickle cell anemia or beta-thalassmia, per Lilly by structurally describing a representative number of small molecules, siRNA or anti-PUM1 antibodies that are capable of treating sickle cell anemia or beta-thalassmia or by describing structural features common to the members of the genus, which features constitute a substantial portion of the genus.
Possession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features. See University of Rochester, 358 F.3d at 927, 69 USPQ2d at 1895.
The court in In re Alonso (Fed. Cir. 2008) citing In re Enzo, Enzo, 323 F.3d at 969 stated that
[F]or purposes of satisfying the written description requirement, it is not enough merely to disclose a method of making and identifying compounds capable of being used to practice the claimed invention.
It is noted that AbbVie v. Janssen Biotech and Centocor Biologics (Fed. Cir. 2014) confirms a strong Post-Ariad Written Description requirement - especially with regard to genus-species claim situations. In the decision, Judge Lourie focuses particularly on the alleged infringing antibodies and notes that: [While] AbbVie patents need not describe the allegedly infringing [compound] in exact terms . . . [t]he patents must at least describe some species representative of antibodies that are structurally similar to [the accused compound]. Because the patent document lacked any such structural description, the court confirmed that the corresponding claims were invalid under 112(a). In discussing the case, Judge Lourie was clear that one problem here is that the invention was described in terms of its function rather than its structure. Lourie writes:
Functionally defined genus claims can be inherently vulnerable to invalidity challenge for lack of written description support, especially in technology fields that are highly unpredictable, where it is difficult to establish a correlation between structure and function for the whole genus or to predict what would be covered by the functionally claimed genus.
The Court has indicated in Amgen Inc vs Sanofi ( 2017-1480, Fed Cir, 2017) that the disclosure of a well characterized antigen is insufficient for an adequate written description of the antibody that binds the antigen. The Court stated that “an adequate written description must contain enough information about the actual makeup of the claim products – a precise definition such as by structure, formula, chemical name, physical properties, or other properties, of species falling within the genus sufficient to distinguish the genus from other material,” which may be present in “function “terminology “when the art has established a correlation between structure and function” (page 17, 1st paragraph). The Court went on to indicate that knowledge of the chemical structure of an antigen does not tell you anything about the structure of the antibody (Id).
In this case, the specification does not appear to describe any small molecules, siRNA or anti-PUM1 antibodies that are capable of treating sickle cell anemia or beta-thalassmia and thus does not satisfy either the Lilly nor Enzo standards Thus, the specification does not appear to describe any species within the genus of inhibitors of PUM1 that are capable of treating sickle cell anemia or beta-thalassmia. There are insufficient structural features common to all members of the genus of inhibitors of PUM1 that are capable of treating sickle cell anemia or beta-thalassmia. However, the specification does not disclose sufficient information on the structural function relationship to identify the claimed genus of inhibitors of PUM1 that are capable of treating sickle cell anemia or beta-thalassmia. One of ordinary skill in the art would not be able to identify the broad claimed genus of inhibitors of PUM1 that are capable of treating sickle cell anemia or beta-thalassmia.
Thus, the specification does not provide an adequate written description of the genus of inhibitors of PUM1 that are capable of treating sickle cell anemia or beta-thalassmia that is required to practice the claimed invention. Applicants have not described the genus of inhibitors of PUM1 that are capable of treating sickle cell anemia or beta-thalassmia sufficiently to show they had possession of the claimed genus. Since the disclosure fails to provide sufficient relevant identifying characteristics, and because the genus is highly variant, one of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of species to describe the genus as broadly claimed.
Summary
No claims allowed.
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/MARK HALVORSON/ Primary Examiner, Art Unit 1646