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 .
Please note that the EXAMINER for this Application has CHANGED.
This action is Non-Final.
The Applicants’ Amendment to the Claims filed on August 6, 2025 is entered.
Election/Restrictions
Applicant’s election without traverse of invention Group III (e.g., claims 27-30, and 35-36) and “CSPα polypeptide” as the species in the reply filed on 12/23/2024 is as previously acknowledged. Note that claims 28-30 and 35-36 are presently cancelled and base claim 27 is amended.
New claims 38-51 are include in Group III.
New claims 39, 43, and 47 are withdrawn to non-elected species.
Claim status
Claims 2-8, 11-16, 19, 21-26, and 28-37 are canceled.
Claims 38-51 are new. Claims 1, 9-10, 17-18, 20, 27, and 38-51 are pending.
Claims 1, 9-10, 17-18, and 20 are withdrawn to non-elected invention group.
Claims 39, 43, and 47 are withdrawn to non-elected species.
Claims 27, 38, 40-42, 44-46, and 48-51 are under examination.
Priority
This US Application 17/606,371 is a 371 of PCT/CA2020/050538 filed on 04/24/2020 and claims US priority benefit of US Provisional 62/839,001 filed on 04/26/2019.
Response to Amendment
Any/all objections and rejections made in the previous office action and not repeated in this office action are withdrawn in view of the Applicants’ Amendment to the Claims filed on August 6, 2025.
Claim Objections
Claim 27 is objected to because of the following informalities: Claim 27 recites “DNA Dna JC7” which appears to intend “Dna JC7. Appropriate correction is required.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 27, 38, 40-42, 44-46, and 48-51 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural phenomenon being a nature based product without significantly more.
The claims recite an extracellular vesicle comprising
a DnaJ domain-containing protein chaperone wherein the DnaJ domain-containing protein chaperone comprises a CSPα polypeptide and
an agent useful for treatment of a CNS disease or disorder. However, extracellular vesicles (EVs) containing a DnaJ domain-containing protein chaperone wherein the DnaJ domain-containing protein chaperone comprises a CSPα polypeptide and a polypeptide agent (useful for treatment of a CNS disease or disorder) are nature-based products found in human cells, as evidenced by Deng et al (“Neurons Export Extracellular Vesicles Enriched in Cysteine String Protein and Misfolded Protein Cargo” Scientific Reports, published online April 19, 2017; pages 1-12). See 2019 Revised Patent Subject Matter Eligibility Guidance published in the Federal Register (84 FR 50) on January 7, 2019).
This judicial exception is not integrated into a practical application because the claims read on a naturally occurring product without significantly more. Deng et al disclose that they isolated EV microvesicles from human cells and that these EVs contained the functional CSPα polypeptide and that the functional CSPα polypeptide was itself an agent useful for treatment of a CNS disease or disorder. An alternative interpretation is that the misfolded polypeptides within these EVs are a type of agent useful for treatment of a CNS disease or disorder in that the removal of such misfolded polypeptides is essential for proper CNS functioning over time. (See Deng et al 2017).
The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because all of the claimed elements are present in the naturally occurring product. .
Further, the claimed product does not include any additional elements because the intended use of the agent “useful for treatment of a CNS disease or disorder” encompasses naturally occurring cargo. (See Deng et al, Abstract). Further, it is noted that the vesicle does not have any additional elements to the exception because the “agent” is construed to encompass a natural cargo of the vesicle. (See Deng et al, Abstract).
Further, regarding claims 40-42, and 44-46, these claims require CSPα polypeptides comprising specific amino acid SEQ ID NO: 1 or DNA sequence SEQ ID NO: 2 encoding such human CSPα polypeptide. As evidenced by attached STIC SEQ ID report, the SEQ ID NOs: 1 and 2 for human CSPα polypeptides in claims 40-42, and 44-46 read on the naturally occurring for human CSPα polypeptide sequence and DNA sequence encoding such. (See attached SCV STIC ID report RESULT 1 S70515 cysteine string protein 1 – human C; Species: Homo sapiens (man) C; Date: 11-Mar-1998 #sequence_revision 17-Apr-1998 #text_change 09-Jul-2004 C; Accession: S70515; S70516 R; Coppola, T.; Gundersen, C. FEBS Lett. 391, 269-272, 1996 A; Title: Widespread expression of human cysteine string proteins.).
Regarding claims 48-50, Deng et al disclose that the extracellular vesicle contains a cargo of naturally occurring misfolded protein. Such cargo meets the limitation of a polypeptide agent useful for treatment of a CNS disease or disorder because Deng et al disclose that the CSPα -mediated removal of toxic proteins (cargo) via EVs plays a central role in synaptic proteostasis and CSPα thus represents a potential therapeutic target for neurogenerative diseases.
Regarding claim 51, the size of the vesicle being 180-240 nm is the natural size of an extracellular vesicle, especially the type of EV called a microvesicle and Deng et al disclose the EVs were microvesicles. (See instant specification para 0152; especially FIG 2).
Claim Rejections - 35 USC § 112
Written Description – updated for amendment
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.
Currently amended claims 27, 38, 40-42, 44-46, and 48-51 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 full-scope of the claimed invention.
Claims 27, 38, 40-42, 44-46, and 48-51 are drawn to an extracellular vesicle comprising a DnaJ domain-containing protein chaperone or a fragment thereof and an agent useful for treatment of a CNS disease or disorder, wherein the DnaJ domain-containing protein chaperone comprises a CSPα polypeptide or a functional fragment thereof. Thus, the claims require the critically essential element of an agent useful for treatment of a CNS disease or disorder and a DnaJ domain-containing protein chaperone or a fragment thereof wherein the DnaJ domain-containing protein chaperone comprises a CSPα polypeptide or a functional fragment thereof.
Regarding the CSP polypeptide, both the state of the art before the effective filing date of the presently claimed invention and the instant Specification as originally filed provide support for a DnaJ domain-containing protein chaperone wherein the DnaJ domain-containing protein chaperone comprises a CSPα polypeptide. Further, the Specification supports the species of the fragment of CSPα is CSPα1-112 which is a truncated form comprising amino acid residues 1-112 of the full length polypeptide. Further Deng et al describes some species of functional CSPα and includes CSPα as a type of potential agent useful for treatment of a CNS disease or disorder. See Deng et al (2017, cited above).
However, neither the state of the art nor the instant Specification provide a representative set of species of functional fragments of such proteins/polypeptides encompassed by the broadly claimed genus of fragments so that one of ordinary skill in the art would be able to envision whether a given fragment of such CSPα polypeptide structures would possess the required function as defined in the Specification. For example, the specification discloses that the claim term “fragment” has the following meaning:
[0157] The term “fragment” refers to any part, portion, or segment of a full length protein that retains at least some of the functionality or activity of the full length protein. For example, a fragment of a DnaJ domain-containing protein chaperone retains the functionality required for the methods, the agent delivery vehicle, and the extracellular vesicle disclosed herein. Fragments of a DnaJ domain-containing protein chaperone will preferably have at least 80%, more preferably, at least 90%, and even more preferably, at least 95% amino acid sequence identity with at least one part of the native full length sequence of the DnaJ domain-containing protein chaperone. Fragments of a DnaJ domain-containing protein chaperone will generally be characterized by having the same type of activity as the naturally occurring DnaJ domain containing protein chaperone, such as the ability, in the context of an EV comprising the fragment, to deliver agents across the blood-brain barrier and/or to the CNS. Various fragments of DnaJ domain-containing protein chaperones may be cloned, expressed, and/or purified using molecular and biochemical techniques known in the art. In certain embodiments of the disclosure, the fragment of CSPα is CSPα1-112 which is a truncated form comprising amino acid residues 1-112 of the full length polypeptide. (emphasis added).
In addition regarding sufficient written description for the genus of “agent”, instant claims 48-50, recite subgenus types of agent are a polypeptide, a nucleic acid, and a small molecule drug. Claim 49, specifies a structural protein, an enzyme, or an antibody or antigen-reactive fragment thereof. Claim 50, specifies DNA, RNA, or a derivative thereof. However, neither the state of the art nor the instant Specification provide a sufficient representative set of species of “agents”, polypeptides, nucleic acids, small molecule drugs, or specifically species of structural proteins, enzymes, antibodies, or antigen-reactive fragments or DNA, or RNA, or derivatives thereof. Thus one of ordinary skill in the art would not be able to envision whether a given species of agent, such as a given RNA derivative, or a given antigen-reactive fragment would possess the required function of being useful for treatment of a CNS disease or disorder.
The fundamental factual inquiry is whether the specification conveys with reasonable clarity to those skilled in the art that, as of the filing date sought, applicant was in possession of the invention as now claimed. See, e.g., Vas-Cath, Inc., 935 F.2d at 1563-64, 19 USPQ2d at 1117.
The limited disclosure of the specification and state of the art in view of the vast genus of functional fragments and agents for use in treating a CNS disease or disorder encompassed by the claims does not adequately describe the entire genus of molecules encompassed by the claims.
“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.” Ex parte Kubin, 83 USPQ2d 1410, 1417 (Bd. Pat. App. & Int. 2007) citing University of Rochester, 358 F.3d at 927, 69 USPQ2d at 1895. Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states that “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description' inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that the inventor(s) invented what is claimed.” (See Vas-Cath at page 1116).
Further, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents of the University of California v. Eh Lily & Co., the court stated:
“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. Fiers, 984 F.2d at 1171, 25 USPQ2d at 1606; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284-85 (CCPA 1973) (‘In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus. ..."). Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The MPEP further states that if a biomolecule is described only by a functional characteristic, without any disclosed correlation between function and structure of the sequence, it is “not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence.” MPEP 2163. The MPEP does state that for generic claim the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. MPEP 2163. If the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. See MPEP 2163. Although the MPEP does not define what constitute a sufficient number of representative, the Courts have indicated what do not constitute a representative number species to adequately describe a broad generic. In Gosteli, the Court determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gosteli, 872 F.2d at 1012, 10 USPQ2d at 1618.
In this case, the application does not identify a representative set of specific species of functional fragments or agents so that one of ordinary skill in the art would have been able to envision whether a given species of such was encompassed by the claimed genus.
The court and the Board have repeatedly held (Amgen Inc. v. Chugai Pharmaceutical Co. Ltd.,18 USPQ2d 1016 (CA FC, 1991); Fiers v. Revel, 25 USPQ2d 1601 (CA FC 1993); Fiddes v. Baird, 30 USPQ2d 1481 (BPAI 1993) and Regents of the Univ. Calif. v. Eh Lilly & Co., 43 USPQ2d 1398 (CA FC, 1997)) that an adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it, irrespective of the complexity or simplicity of the method; what is required is a description of the nucleic acid itself.
Thus, one of skill at the time of the invention could not have concluded that the inventor(s) were in possession of the genus of functional fragments or agents as recited in the presently claimed invention.
Response to Argument
The Applicants’ argument filed on August 6, 2025 has been fully considered but is unpersuasive. The applicants argue that claim 27 is amended to recite the limitations from claim 29: “wherein the DnaJ domain-containing protein chaperone comprises one or more of either a CSPα polypeptide or a functional fragment thereof, or a Dna JC7 polypeptide or a functional fragment thereof.” However, this argument is unpersuasive because previous claim 29 was included in the previous rejection for insufficient written description. The applicants argue “that the claims as amended are supported by the specification, and that the application reasonably conveys to one skilled in the art that, at the time the application was filed, the inventors had possession of the claimed invention”. However, the applicants argument is unpersuasive because it provides no reasoning or evidence to support the argument. The applicants argument is unpersuasive for reasons provided in the body of the rejection above.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 27, 38, 40-42, 44-46, and 48-51 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Deng et al as evidenced by Coppola et al (FEBS Lett. 391, 269-272, 1996; “Widespread expression of human cysteine string proteins” (See attached SCV STIC ID report RESULT 1 S70515).
Regarding claims 27, and 38, Deng et al discloses an extracellular vesicle comprising a DnaJ domain-containing protein chaperone or a fragment thereof and an agent useful for treatment of a CNS disease or disorder, wherein the DnaJ domain-containing protein chaperone comprises a CSPα polypeptide or a functional fragment thereof. (See Abstract, entire article, Fig2). Deng et al disclose the EVs contain contains a cargo of naturally occurring misfolded protein. Such cargo meets the limitation of a polypeptide agent useful for treatment of a CNS disease or disorder because Deng et al disclose that the CSPα -mediated removal of toxic proteins (cargo) via EVs plays a central role in synaptic proteostasis. Deng et al disclose that CSPα polypeptide itself meets the limitation of a polypeptide agent useful for treatment of a CNS disease or disorder. Deng et al describes some species of functional CSPα and includes CSPα as a type of potential agent useful for treatment of a CNS disease or disorder. (See pages 1-12; especially page 5, “CSPα promotes/chaperones export of disease-causing proteins”).
Regarding claims 40-42, and 44-46, these claims recite CSPα polypeptides comprising specific amino acid SEQ ID NO: 1 or where the CSPα polypeptides are encoded by DNA sequence SEQ ID NO: 2. As evidenced by attached STIC SEQ ID report to Coppola et al, the instant SEQ ID NO: 1 is 100% identical to the native human CSPα polypeptides. As noted in the instant specification, the CSPα polypeptide of instant SEQ ID NO:1 meets the limitation of being encoded by instant SEQ ID NO:2. Thus Deng et al inherently anticipates the limitations of instant SEQ ID NOs: 1 and 2 in the claims because these are the naturally occurring human CSPα polypeptide.
Regarding claims 48-50, Deng et al discloses that the EVs contain an agent that is a polypeptide. Regarding claim 49, note that the limitation of “polypeptide” is written in the alternative in claim 48. Regarding claim 50, note that the limitation of “nucleic acid” is written in the alternative in claim 48. Specifically, Deng et al disclose the EVs contain contains a cargo of naturally occurring misfolded protein. Such cargo meets the limitation of a polypeptide agent useful for treatment of a CNS disease or disorder because Deng et al disclose that the CSPα -mediated removal of toxic proteins (cargo) via EVs plays a central role in synaptic proteostasis. Deng et al disclose that CSPα polypeptide itself meets the limitation of a polypeptide agent useful for treatment of a CNS disease or disorder. (See pages 1-12; especially page 5, “CSPα promotes/chaperones export of disease-causing proteins”).
Regarding claim 51, Deng et al discloses that the extracellular vesicle is 180-240 nm. For example, the size of the vesicle being 180-240 nm is the natural size of an extracellular vesicle, especially the type of EV called a microvesicle and Deng et al disclose the EVs were microvesicles. (See instant specification para 0152; and Deng et al especially FIG 2).
Conclusion
No claim is allowed.
Related prior art which may be applied in a future office action:
Polyak et al US 11,644,466 filed on March 15, 2013.
Fernandez-Chacon “The Synaptic Vesicle Protein CSPα Prevents Presynaptic Degeneration” (Neuron Vol 42, No.2, April 22, 2004, pages 237-251; IDS ref). The reference discloses that “cysteine string protein α (CSPα) are an abundant synaptic vesicle protein that contains a DNA-J domain characteristic of Hsp40 chaperones. Fernandez-Chacon discloses that CSPα-deficient mice develop a progressive, fatal sensorimotor disorder. They suggest that CSPα acts as a presynaptic chaperone that maintains continued synaptic function, raising the possibility that enhanced CSPα function could attenuate neurodegenerative diseases.
US 20130337463 to Brunden et al.
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/CATHERINE S HIBBERT/ Primary Examiner, Art Unit 1658