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 1-19 are pending.
This application claims priority as a 371 filing of PCT/EP23022/.060774 filed 4/22/2022 which claims priority to foreign application EP 21170264.2 filed 4/23/2021.
Information Disclosure Statement
Information disclosure statements filed 10/19/2023, 7/31/2024, 11/15/2024, 3/13/2025, 4/10/2025 and 12/8/2025 have been identified and the documents considered. The corresponding signed and initialed PTO Form 1449 has been mailed with this action. Initials indicate that the document has been considered even if the reference is lined through. In the case that only an English abstract was identified, this is indicated. Applicants have asserted that no size fee is required.
Claim Objections
Claims 2 and 7-11 are objected to under 37 CFR 1.75 as being a substantial duplicate of claim 1. 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). Claims 2 and 7-11 are drawn to properties that simply describe a use for the vehicle of claim 1. There are no additional properties recited in claims 2 and 7-11 and hence considering the structures are duplicate recitations.
Claim 17 is objected to because of the following informalities: HJHS is abbreviated without the full spelling. Although claims are allowed abbreviations, if an abbreviation is not spell out upon first use in a claim, MPEP §2429 states that Applicant only use abbreviations that are specifically defined in "WIPO Standard ST.25 (1998)" or that are well known and would be clear to someone who had not read the invention description.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 4 and 5 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 4 recites the limitation "the AAV based particle" in claim 1. There is insufficient antecedent basis for this limitation in the claim. Claim 3 does not refer to an AAV particle. For art purposes this will be considered as reading on an AAV viral vector in claim 3.
Claim 5 recites the limitation “the nucleic acid comprising a wildtype Factor IX” in claim 1. There is insufficient antecedent basis for this limitation in the claim. It appears the claim intends comprising to be comprises.
Claim Rejections - 35 USC § 112, first paragraph
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 1-4 and 6-19 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 1 is drawn to a vehicle wherein the vehicle comprises a nucleic acid that encodes a coagulation factor having Factor IX activity. Therefore, the claim is drawn to a molecule claimed by its property. The claim recites a sequence encoding “a coagulation factor” wherein the coagulation factor is claimed in terms of its function as having Factor IX activity. Claims 2 and 7-11 do not alter the structure of the vehicle of claim 1 as they simply recite properties that are desired of the vehicle. Claims 3-6 and 12-14 do not add to the structure in a way the delineates the structure beyond the generic recitation of claim 1. Claims 15-20 are drawn to methods of using but again do not provide structure to delineate a structure specific to the claims. The disclosure only teaches two sequences which are the wild type sequence encoding Factor IX and a hyperactive variants which is Factor IX with has a R338L. These two sequences do not provide a sufficient disclosure of any encoding coagulation factor having Factor IX activity and a hyperactive variant.
Hence, the claims are drawn to a structural molecule that must also have functional properties. However, there is no disclosure of structures that mediate Factor IX activity other than the two single sequences. As well, there is no disclosure of the structural properties that are required of factor with the required functional properties. The claims thus are drawn to a large genus of coagulation factors which are not sufficiently described in the specification. The written description requirement for genus claims may be satisfied through sufficient description of a representative number of species by actual reduction to practice, 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 known or disclosed correlations between function and structure, or by a combination of such characteristics sufficient to show that the applicant was in possession of the claimed genus.
To this end, the MPEP provides such guidance (emphasis added). If the application as filed does not disclose the complete structure (or acts of a process) of the claimed invention as a whole, determine whether the specification discloses other relevant identifying characteristics sufficient to describe the claimed invention in such full, clear, concise, and exact terms that a skilled artisan would recognize applicant was in possession of the claimed invention. For example, if the art has established a strong correlation between structure and function, one skilled in the art would be able to predict with a reasonable degree of confidence the structure of the claimed invention from a recitation of its function. Thus, the written description requirement may be satisfied through disclosure of function and minimal structure when there is a well-established correlation between structure and function. In contrast, without such a correlation, the capability to recognize or understand the structure from the mere recitation of function and minimal structure is highly unlikely. In this latter case, disclosure of function alone is little more than a wish for possession; it does not satisfy the written description requirement. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406 (written description requirement not satisfied by merely providing "a result that one might achieve if one made that invention"); In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming a rejection for lack of written description because the specification does "little more than outline goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate"). Compare Fonar, 107 F.3d at 1549, 41 USPQ2d at 1805 (disclosure of software function adequate in that art).
Claim Rejections - 35 USC § 112, first paragraph
The following is a quotation of the first paragraph of 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 15-19 are rejected under 35 U.S.C. 112, first paragraph, because the specification, while being enabling for a method of treating hemophilic arthropathy of a joint in a patient with hemophilia B prior to synovitis, the method comprising 5x1012 or 2x1013 vg/kg AAV5 intravenously, the AAV comprising a nucleic acid sequence encoding Factor IX or the hyperactive variant that comprises a R338L mutation in the wild type sequence wherein the nucleic acid sequence is operably linked to a promoter, does not reasonably provide enablement for any other embodiment. 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.
The test of enablement is whether one skilled in the art could make and use the claimed invention from the disclosures in the patent coupled with information known in the art without undue experimentation (United States v. Telectronics, Inc., 8 USPQ2d 1217 (Fed. Cir. 1988)). Whether undue experimentation is required is not based on a single factor but is rather a conclusion reached by weighing many factors (See Ex parte Forman, 230 USPQ 546 (Bd. Pat. App. & Inter, 1986) and In re Wands, 8USPQ2d 1400 (Fed. Cir. 1988); these factors include the following:
1) Nature of invention. The instant claims are drawn to a method of gene therapy for joint arthropathy resulting from hemophilia B.
2) Scope of the invention. The scope of the invention is extremely broad in that the method includes preventing, arresting or treating hemophilic arthropathy of the joint in the patient wherein the delivery is of any gene therapy vehicle and the method of administration is any.
3) Number of working examples and guidance. Three examples detail Clinical trials of patients with hemophilia B. Delivery of 5x1012 or 2x1013 vg/kg AAV5 intravenously led to improvement in a range of subjects .
4) State of the art. Hemophilic arthropathy is a severe, disabling joint disease caused by repeated bleeding into the joints in people with hemophilia, leading to chronic pain and reduced joint mobility. This damage occurs because with hemophilia, cartilage and bone are broken down due to loss of blood triggering inflammation and joint remodeling. Hemophilia B is a X-linked disorder caused by deficiency in coagulation factors FVIII and FIX (see Gualtierotti et al, J Thromb Haemost, page 2113, col 1-2). Recurrent joint bleeding leads to synovitis and osteochondral damage and the art teaches, (Gualiterotti et al, bridging ¶ page 2117-2118).
Once it has become established, synovitis cannot be treated with factor replacement alone and it has been suggested TNFα blockade with monoclonal antibodies may be a means of controlling synovitis and potentially reducing joint bleeding.92 However, this cannot be considered an option until the pathophysiological mechanisms underlying the development and progression of hemophilic arthropathy have been defined, and the precise role of pro-inflammatory cytokines has been established. F
5) Unpredictability of the art. As a first issue, the claimed molecule for therapy is a coagulation factor with FIX activity. As set forth above, this is a genus claim but the disclosure and art only disclose Factor IX. Furthermore, for gene therapy, the delivery of any vehicle has not shown plausible for successful therapy (see for example Sosnowska-Sienkiewicz and Januszkiewicz-Lewandowska, page 8-9). AAV has risen as a top delivery agent using doses acceptable to achieve sustained transgene expression (see page 7-8 of Sosnowska-Sienkiewicz and Januszkiewicz-Lewandowska). But, the art teaches that treatment therapies rely on identifying proper delivery vehicle methods. This is complicated by the lack of an expression control sequence to direct expression.
Secondly, the claims are also directed to use of the variants in methods of treating hemophilic arthropathy wherein the subjects include those for whom the disease must be prevented. This requires predicting the subjects that would require treatment which would be highly unpredictable. In humans, the claimed diseases are usually established before therapy is offered. The specification does not adequately teach how to effectively predict for whom prevention would be required. One establishes a large genus of target subjects for whom the method is intended, however, establishing whether a person or persons actually requires the treatment is a highly unpredictable art. Screening procedures for indications of those requiring inhibition of the onset of disease are unknown and highly prejudicial leading to conditions in which those who require the treatment cannot be distinguished from those who do not. The physiological art is recognized as unpredictable. (MPEP 2164.03.) In cases involving predictable factors, such as mechanical or electrical elements, a single embodiment provides broad enablement in the sense that, once imagined, other embodiments can be made without difficulty and their performance characteristics predicted by resort to known scientific laws. In cases involving unpredictable factors, such as most chemical reactions and physiological activity, the scope of enablement obviously varies inversely with the degree of unpredictability of the factors involved. In this case, applicants exacerbate the unpredictability of the art by reciting subjects to be targeted for whom the disease must be prevented.
6) Undue experimentation. The claims have been evaluated in light of the art at the time of filing and found not to be commensurate in scope with the specification. MPEP 2164.05 teaches, “However, the examiner should carefully compare the steps, materials, and conditions used in the experiments of the declaration with those disclosed in the application to make sure that they are commensurate in scope; i.e., that the experiments used the guidance in the specification as filed and what was well known to one of skill in the art. Such a showing also must be commensurate with the scope of the claimed invention, i.e., must bear a reasonable correlation to the scope of the claimed invention. The invention recites use of a broad group of sequence. Given the unpredictability of the art, the poorly developed state of the art with regard to predicting the structural/ functional characteristics of antagonists, the lack of adequate working examples and the lack of guidance provided by applicants, the skilled artisan would have to have conducted undue, unpredictable experimentation to practice the claimed invention.”
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-4 and 6-16 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Meisbach et al, (Blood Thrombosis and Hemostasis, 2018, pages 1022-1031, IDS filed 11/15/2024).
Meisbach et al teach an AAV5 vector encoding Factor IX. This meets the limitations of claims 1, 3 and 4 (see abstract). Claims 2 and 7-11 recite properties desired of the vehicle but the claims do not add structure that delineates that of claim 1 from what is desired and hence the properties are believed to be inherent in the vehicle of Meisbach. The sequence is under control of a liver specific promoter (see e.g. abstract).
A single dose of 5x1012 or 2x 1013 genome copies of the AAV vector was administered to subjects with hemophilia B and hemophilic arthropathy (see page 1023, col 1, last ¶). The composition is a pharmaceutical composition therefore for intravenous administration (see page 1022, col 2). It is in liquid form (see page 1023, col 2). Therefore, the limitations of claims 12-16 are met.
Claims 1-3 and 5-16 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Monahan et al, (Human Gene Therapy, 2015, pages 69-81, IDS filed 11/15/2024).
Monahan et al teach an AAV vector encoding hyperactive Factor IX (R338L). This meets the limitations of claims 1-3 and 5 (see abstract). Claims 2 and 7-11 recite properties desired of the vehicle but the claims do not add structure that delineates that of claim 1 from what is desired and hence the properties are believed to be inherent in the vehicle of Monahan. The sequence is under control of a promoter (see e.g. page 70, col 2).
A single dose of 2x 1012 genome copies of the AAV vector was administered to mice with hemophilia B and hemophilic arthropathy (see abstract). The composition is a pharmaceutical composition therefore for intravenous administration and hence as it is injected by tail vein is known to be in liquid form (see page 70, col 2). Therefore, the limitations of claims 12-16 are met. The method was intended to be a study for human administration (see page 70, col 1).
Claims 1-3 and 5-19 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Dumont et al, (U.S. 20190381149).
Dumont teaches AAV vectors to deliver FIX or a hyperactive variant to a subject (see e.g. ¶0148 and 0294). This meets the limitations of claims 1-3, 5 and 16. Claims 2 and 7-11 recite properties desired of the vehicle but the claims do not add structure that delineates that of claim 1 from what is desired and hence the properties are believed to be inherent in the vehicle of Dumont. The sequence is under control of a promoter (see ¶0298).
The composition is administered by intravenous and as part of a pharmaceutical composition (see ¶0101) as recited in claims 12-13 and 16. It can be liquid (see ¶0201) as recited in claim 14
Dumont teaches HJHS 2.1 (also called standard HJHS in Dumont) to monitor joint health improvement (see ¶0172). The HJHS is measured before therapy and after wherein it is lower after treatment (see e.g. ¶0177). Measurements were after at least a year (see e.g. ¶0324 and table 4) as recited in claim 19.
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 Ockert, 245 F.2d 467, 114 USPQ 330 (CCPA 1957); and In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970).
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. See 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);and, 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) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the conflicting application or patent is shown to be commonly owned with this application. See 37 CFR 1.130(b).
Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b).
Claims 1-4 and 6-16 are provisionally rejected under the judicially created doctrine of obviousness-type double patenting as being unpatentable over claims 1-6 of copending Application No. 17/213,897.
An obviousness-type double patenting rejection is appropriate where the conflicting claims are not identical, but an examined application claim is not patentably distinct from the reference claims because the examined claim is either anticipated by, or would have been obvious over, the reference claims. Although the conflicting claims are not identical, they are not patentably distinct from each other because the cited claims of the instant invention are generic to all that is recited in claims 1-6 of copending Application No. 17/213,897. That is, the cited claims of copending Application No. 17/213,897anticipate and fall entirely within the scope of the rejected claims of the instant application. Specifically, both claims are drawn to a nucleic acid i.e. AAV that encodes a factor having Factor IX activity wherein the copending claims that encode FIX meet. SEQ ID NO:14 of copending Application No. 17/213,897 is the hyperactive mutant claimed in the instant claims. Claims 2 and 7-11 of the instant application claim desired uses of the vector but do not otherwise limit the vector claimed in claim 1. Hence, they are inherently encompassed by copending Application No. 17/213,897. Administration in the copending Application No. 17/213,897as a suspension places the composition in the format of instant claims 12-14 and 16.
Additionally, if a patent resulting from the instant claims was issued and transferred to an assignee different from the assignee holding the copending Application No. 17/213,897, then two different assignees would hold a patent to the claimed invention of copending Application No. 17/213,897, and thus improperly there would be possible harassment by multiple assignees.
This is a provisional obviousness-type double patenting rejection because the conflicting claims have not in fact been patented.
Claims 1-19 are provisionally rejected under the judicially created doctrine of obviousness-type double patenting as being unpatentable over claims 1, 2, 4, 6-10, 12-14, 16 and 20-25 of copending Application No. 19/046,845. This application is a divisional of the parent application 18/508,998 but is a continuation filing of the instant claims. It is noted that the copending claims have been found allowable and the issue fee paid on 1/8/2026. The provisional status of the rejection will be non-provisional upon issuance of a patent number.
An obviousness-type double patenting rejection is appropriate where the conflicting claims are not identical, but an examined application claim is not patentably distinct from the reference claims because the examined claim is either anticipated by, or would have been obvious over, the reference claims. Although the conflicting claims are not identical, they are not patentably distinct from each other because the cited claims of the instant invention are generic to all that is recited in claims 1, 2, 4, 6-10, 12-14, 16 and 20-25 of copending Application No. 19/046,845. That is, the cited claims of copending Application No. 19/046,845 anticipate and fall entirely within the scope of the rejected claims of the instant application. Specifically, copending Application No. 19/046,845 and the instant claims are drawn to vectors i.e. AAV5 and methods of treating hemophilia with a normal of hyperactive FIX active factor. It is noted that instant claims 2 and 7-11 recite desired properties that do not alter the structure of the nucleic acid and hence are inherently encompassed.
Additionally, if a patent resulting from the instant claims was issued and transferred to an assignee different from the assignee holding the copending Application No. 19/046,845, then two different assignees would hold a patent to the claimed invention of copending Application No. 19/046,845, and thus improperly there would be possible harassment by multiple assignees.
This is a provisional obviousness-type double patenting rejection because the conflicting claims have not in fact been patented.
Claims 1, 2, 5, 6 and 7-16 are rejected under the judicially created doctrine of obviousness-type double patenting as being unpatentable over claims 1-16 of RE50,288.
An obviousness-type double patenting rejection is appropriate where the conflicting claims are not identical, but an examined application claim is not patentably distinct from the reference claims because the examined claim is either anticipated by, or would have been obvious over, the reference claims. Although the conflicting claims are not identical, they are not patentably distinct from each other because the cited claims of the instant invention are generic to all that is recited in claims 1-16 of RE50,288. That is, the cited claims of U.S. Patent RE50,288 and fall entirely within the scope of the rejected claims of the instant application. Specifically, RE50,288 is drawn to proteins encoded by the nucleic acid of the instant claims as well as the nucleic acids and overlapping methods of using the claimed product. Coagulopathy as defined in the copending application is hemophilia B and hence, the methods of treatment and pharmaceuticals of the instant claims apply.
Additionally, if a patent resulting from the instant claims was issued and transferred to an assignee different from the assignee holding the RE50,288, then two different assignees would hold a patent to the claimed invention of RE50,288, and thus improperly there would be possible harassment by multiple assignees.
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/MARIA MARVICH/Primary Examiner, Art Unit 1634