DETAILED ACTION
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 .
Claims 1, 2, 8-13, 15, 17, 18, 22, 25, 26, 30, 31 and 160-166 were previously pending.
Claims 1, 8, 11, 12, 165, and 166 have been amended and claim 167-176 have been added by Applicants’ amendment filed on 09/19/2025.
Therefore, claims 1, 2, 8-13, 15, 17, 18, 22, 25, 26, 30, 31, and 160-176 are pending and under examination in the present Official Action.
Status of Application/Amendments/Claims
Applicant’s response filed on 19 September, 2025 has been considered. Rejections and/or objections not reiterated from the previous office action mailed 20 March, 2025 are hereby withdrawn.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Priority
Applicant’s claim for the benefit of a prior-filed application PRO 62/883,319 and PRO 62/947,228 filed on 06 August, 2019 and 12 December, 2019, respectively, under 35 U.S.C 119(e) or under 35 U.S.C 120, 121 or 365(c) is acknowledged.
Accordingly, the effective priority date of the instant application is granted as 06 August, 2019.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 22 September, 2025, and 17 November, 2025 were received. The submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Drawings
The drawings submitted on 21 December, 2020 are accepted by the Examiner.
Withdrawn Objections/Rejections in view of Applicant’s Arguments or Amendments
35 U.S.C. 112, (d)
The rejection of claims 8-10 under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends is withdrawn in view of Applicant’s amendments to the claims.
Claim Rejections - 35 USC § 103
The rejection of claims 1-2, 8-13, 15, 17-18, 22, 25, 30-31, and 162-166 under 35 U.S.C. 103 as being unpatentable over Kojima et al. (Nature communications 9.1 (2018): 1305 ; hereinafter “Kojima”, reference of record) in view of Glorieux et al. (Free Radical Biology and Medicine 87 (2015): 84-97., hereinafter “Glorieux”), Huber et al., (US 2014/0193408 (Published: 10 July, 2014; hereinafter “Huber”), Rodriguez, et al. (Science 339.6122 (2013): 971-975. (hereinafter “Rodriguez”), Spicer et al. (Chemical society reviews 47.10 (2018): 3574-3620; hereinafter “Spicer”, reference of record), and Steel et al. (Trends in pharmacological sciences 33.1 (2012): 35-41., hereinafter “Steel”) is withdrawn in view of Applicant’s arguments.
Applicant argues that one would not have been motivated to use the CD47 of Huber in a membrane-bound context because Huber teaches soluble fusobodies and does not teach insertion of said fusobodies in the membrane. Remarks, at 13. Applicant continues that the solubility is a stated advantage in Huber, thus, a person having ordinary skill in the art would not be motivated to remove said stated advantage by inserting the soluble fusobody of Huber into the membrane of an exosome, nor would they have had a reasonable expectation of success. This argument is found to be persuasive and the prima facie obviousness in view of Huber is withdrawn.
The rejection of claims 26 and 160-161 under 35 U.S.C. 103 as being unpatentable over Kojima et al. Nature communications 9.1 (2018): 1305 (hereinafter “Kojima”, reference of record), Glorieux et al. (Free Radical Biology and Medicine 87 (2015): 84-97., hereinafter “Glorieux”), US 2014/0193408 (Published: 10 July, 2014) (hereinafter “Huber”), Rodriguez, Pia L., et al. Science 339.6122 (2013): 971-975. (hereinafter “Rodriguez”), as applied to claim 1 above in further view of Boukany et al. (Nature nanotechnology 6.11 (2011): 747-754 ;hereinafter “Boukany”, reference of record) is withdrawn in view of Applicant’s arguments.
Applicant argues that one would not have been motivated to use the CD47 of Huber in a membrane-bound context because Huber teaches soluble fusobodies and does not teach insertion of said fusobodies in the membrane. Remarks, at 13. Applicant continues that the solubility is a stated advantage in Huber, thus, a person having ordinary skill in the art would not be motivated to remove said stated advantage by inserting the soluble fusobody of Huber into the membrane of an exosome, nor would they have had a reasonable expectation of success. This argument is found to be persuasive and the prima facie obviousness in view of Huber is withdrawn.
Maintained Grounds of Objection/Rejections in Response to Applicant’s Arguments or Amendments
Claim Rejections - 35 USC § 112b
Claims 1-2, 8-13, 15, 17-18, 22, 25-26, 30-31 and 160-166 remain rejected and claims 167-176 are newly 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. This rejection is necessitated by Applicant’s amendments to the claims
Claim 1 is indefinite in its recitation of “said extracellular vesicle released from said extracellular donor cell” in 12th and 13th lines of the claim. Applicant amended claim 1 to recite “said” in place of “an” before “extracellular vesicle”. This rendered the claim indefinite because there is insufficient antecedent basis for “said extracellular vesicle” in the claim. Claims 2, 8-13, 15, 17, 18, 22, 25, 26, 30, 31, and 160-176 are further rejected for their dependency on a rejected base claim. It is noted that, since claim 1 is the independent claim from which all other claims depend, any other claim which recites “said extracellular vesicle” necessarily also lacks sufficient antecedent basis in the claims.
Claim 12 depends indirectly from claim 1 and recites “extracellular vesicles” in the second line of the claim and “said extracellular vesicles” in the third line of the claim. There is not proper antecedent bases for the recitation of “extracellular vesicles” in the claim. The parent claim recites “said extracellular vesicle released from said extracellular vesicle donor cell” which also lacks antecedent basis. The metes and bounds of the claim are indefinite.
Claim 25 is also rejected for being indefinite because “said extracellular vesicle” lacks antecedent basis in claim 25 or within claim 1 from which it depends.
Claim 170 is indefinite in its recitation of “substantially intact messenger RNA” . The term " substantially " in claim 170 is a relative term which renders the claim indefinite. The term " substantially " is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Appropriate action is required.
Nonstatutory Double Patenting
Applicant’s request for abeyance is acknowledged. However, until allowable claims are identified, or a terminal disclaimer is filed, the following rejection will continue to apply.
Claims 1-2, 8-13, 15, 17-18, 22, 25-26, 30-31 and 160-166 remain rejected and new claims are 167-176 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-26 of US Patent No. 11674130 in view of Huber and Rodriguez, Although the claims at issue are not identical, they are not patentably distinct from each other because the patented claims would render obvious the instant claims if they were available as prior art.
This rejection has been modified.
Claim 1 of US Patent 11674130 is directed to:
A method of producing extracellular vesicles (EVs) comprising at least one RNA transcribed from DNA, comprising:
(a) providing an electroporation biochip, the electroporation biochip comprising: (i) donor cells in contact with a first surface of the electroporation biochip and secreting a baseline amount of secreted extracellular vesicles (EVs);(ii) a buffer comprising the DNA, wherein the buffer comprising the DNA is in contact with a second surface of the electroporation biochip; and (iii) a plurality of channels that connect the first surface of the electroporation biochip with the second surface of the electroporation biochip, wherein the plurality of channels are positioned such that individual channels of the plurality of channels contacts individual donor cells of the donor cells in contact with the first surface of the electroporation biochip;
(b) applying a pulsed electric field to the electroporation biochip wherein the pulsed electric field is applied as a plurality of pulses wherein each pulse is at least one millisecond in length and such that the pulsed electric field delivers the DNA to the donor cells to produce transfected donor cells, wherein the pulsed electric field causes the transfected donor cells to secrete 10-fold to 100-fold more extracellular vesicles (EVs) compared to the baseline amount of secreted extracellular vesicles (EVs) and wherein the transfected donor cells release extracellular vesicles (EVs) comprising the at least one RNA transcribed from the DNA; and (c) collecting the extracellular vesicles (EVs) comprising the at least one RNA transcribed from the DNA.
Claim 1 of the invention is directed to a method of producing an extracellular vesicle, said method comprising:
a) electroporating an extracellular vesicle donor cell with at least one polynucleotide, wherein said at least one polynucleotide encodes a hybrid targeting polypeptide that comprises: (i) an adapter polypeptide comprising a transmembrane domain and an extracellular domain, wherein said adapter polypeptide is a CD47 polypeptide having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 1; and (ii) a heterologous targeting domain that is covalently linked to said extracellular domain of said adapter polypeptide;
b) incubating said extracellular vesicle donor cell under conditions such that (i) said hybrid targeting polypeptide is expressed in said extracellular vesicle donor cell and (ii) said hybrid targeting polypeptide is incorporated into said extracellular vesicle released from said extracellular vesicle donor cell such that said transmembrane domain of said adapter polypeptide is incorporated in a membrane of said extracellular vesicle; and
c) collecting said extracellular vesicle released from said extracellular vesicle donor cell, wherein said extracellular vesicle comprises said hybrid targeting polypeptide,
wherein said heterologous targeting domain is a cell surface marker binding domain; and wherein said transmembrane domain of said adapter polypeptide is at least 90% identical to a transmembrane domain of said CD47 polypeptide, wherein said transmembrane domain of said CD47 polypeptide corresponds to amino acid positions of 142-162, 177-197, 208-228, 236-256, or 269-289 of SEQ ID NO: 1; and
wherein said extracellular domain of said adapter polypeptide is at least 90% identical to a domain corresponding to amino acid positions 19-141, 198-207, or 257-268 of SEQ ID NO: 1.
Claim 1 of the invention essentially differs from claim 1 of the Patent No. 11674130 by not requiring a plurality of pulses wherein each pulse is at least one millisecond in length and wherein the pulsed electric field causes the transfected donor cells to secrete 10-fold to 100-fold more extracellular vesicles (EVs) compared to the baseline amount of secreted extracellular vesicles (EVs). In relation to these limitations, the method of claim 1 of the Patent No. 11674130 is species of the instant claim 1 and anticipates claim 1.
In relation to the recitation of a transmembrane domain of being at least 90% identical to a transmembrane domain of a CD47 polypeptide wherein said transmembrane domain of said CD47 polypeptide corresponds to amino acid positions of 142-162, 177-197, 208-228, 236-256, or 269-289 of SEQ ID NO: 1 and wherein said extracellular domain of said adapter polypeptide is at least 90% identical to a domain corresponding to amino acid positions 19-141, 198-207, or 257-268 of SEO ID NO: l in claim 1, claim 1 of US Patent 11674130, does not required the claimed sequences.
However, Huber and Rodriguez render obvious the claimed (i) an adapter polypeptide comprising a transmembrane domain and an extracellular domain; and (ii) a heterologous targeting domain that is covalently linked to said extracellular domain of said adapter polypeptide of instant claim 1.
Huber teaches a sequence that is 100% identical to a domain corresponding to amino acid positions 19-141 of instant SEQ ID NO: 1 (Huber, SEQ ID NO: 3; Table 7B).
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Huber teaches that the sequence is the extracellular domain of human CD47 and also discloses a sequence 100% identical to the full length human CD47 containing the CD47 transmembrane domain as in instant claims 1 and 165 (Huber, SEQ ID NO: 2; Table 7B; Table 7A; [0080]-[0085]). Huber teaches “fusobodies” which are fusion proteins comprised of human CD47 fused to various antibody domains via the C-terminus of CD47 (Huber, Table 7A; [0070]). Huber teaches that using the CD47 extracellular domain is useful for cell transplantation through evasion of phagocytosis (Huber, [0010]). Huber also teaches that an advantage of the fusobodies containing full length CD47 is that they possess specificity for multiple antigens (Huber, [0021]). Huber, thus, discloses the use of human CD47 covalently linked to a heterologous targeting domain and teaches that such a fusion polypeptide is advantageous for targeting multiple antigens and that CD47 in particular is advantageous for use in fusion proteins for evading phagocytosis. Likewise, Rodriquez teaches that human CD47 is a putative marker of self in mammals (Rodriguez, page 971, second full paragraph) and that human CD47 is advantageous for expression on nanoparticles because it prevents clearance which prolongs circulation of the nanoparticles and can allow for increased accumulation in tumor cells when the nanoparticles are also engineered to target tumors (Rodriguez, Fig. 1; Fig. 2).
Thus, a person having ordinary skill in the art before the effective filing date of the claimed invention would have been motivated by the teachings of Huber and Rodriguez to express a human CD47 fusion proteins comprised of amino acid sequences 100% identical to those claimed in instant claim 1 as the RNA transcribed from DNA in claim 1 of claim 1 of the Patent No. 11674130 to decrease uptake and clearance of the secreted extracellular vesicles (EVs) by non-target cells and increase targeting of the exosomes to target cells.
The applicant has not provided arguments traversing the instant grounds of rejection, but instead has asked that the rejections be held in abeyance until there is an indication of allowable subject matter. Applicant’s request is not a proper response to the rejections of record as it neither traverses the grounds of rejection by providing specific arguments, nor indicates that a terminal disclaimer has or will be filed to overcome the rejection. As such, the rejections of record stand.
Claim Rejections - 35 USC § 112a
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 1-2, 8-13, 15, 17-18, 22, 25-26, 30-31 and 160-166 remain rejected and claims 167-176 are newly 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 claims contain 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 claimed invention.
The instant claims are broadly directed to an extracellular vesicle comprising a polynucleotide which encodes a hybrid targeting polypeptide wherein the hybrid targeting polypeptide comprises a heterologous targeting domain and an adapter polypeptide which is a CD47 polypeptide having at least 90% identity to an amino acid sequence set forth in SEQ ID NO: 1, and wherein the adapter polypeptide comprises (1) a genus of transmembrane polypeptides that are at least 90% identical to a transmembrane domain of a CD47 polypeptide wherein said transmembrane domain of said CD47 polypeptide corresponds to amino acid positions of 142-162, 177-197, 208-228, 236-256, or 269-289 of SEQ ID NO: 1 and (2) a genus of extracellular domains that are at least 90% identical to a domain corresponding to amino acid positions 19-141, 198-207, or 257-268 of SEQ ID NO: 1 with the function that the targeting polypeptide that is covalently linked to said extracellular domain of said adapter polypeptide (e.g., a CDX peptide (FKESWREARGTRIERG (SEQ ID NO: 104)) for U87 targeting, and a CREKA for GL261 targeting) is expressed in extracellular vesicles released from an extracellular vesicle donor cell. Thus, the instant claims are broadly directed to a genus of extracellular domain of said adapter polypeptide that are functionally capable of expressing targeting polypeptide in extracellular vesicle donor cell and in secreted extracellular vesicles. Applicants have disclosed fusion proteins comprising a single species of CD47 that has the functional property of expression on secreted exosomes (Specification, [00188]-[00189]; [00195]-[00197]; SEQ ID NO: 1; [0081]). It is noted that the only disclosed species is full-length human CD47 and no species are disclosed having anything less than 100% identity to human CD47, let alone having either just the transmembrane domain or just the extracellular domain of human CD47.
Applicants are claiming an undefined number of polypeptides having an adapter polypeptide which has 90% sequence identity to “an amino acid sequence set forth in SEQ ID NO: 1”. This amended language reads on any polypeptide having 9 out of any 10 amino acid long stretch within SEQ ID NO: 1 itself. The polypeptide of amended claim 1 also must encode (1) a genus of transmembrane polypeptides that are at least 90% identical to a transmembrane domain of a CD47 polypeptide wherein said transmembrane domain of said CD47 polypeptide corresponds to amino acid positions of 142-162, 177-197, 208-228, 236-256, or 269-289 of SEQ ID NO: 1 and (2) a genus of extracellular domains that are at least 90% identical to a domain corresponding to amino acid positions 19-141, 198-207, or 257-268 of SEQ ID NO: 1 (taken together, claim 1 reads on a polypeptide having a sequence having 90% identity to just amino acids 142-162 and just amino acids 198-207 of SEQ ID NO: 1). The specification prophetically discloses that such an undefined genus will have the function of exosome expression (Specification, [0082]). However, the specification is silent as to what portions of the CD47 polypeptide are responsible for the functional property of exosome expression observed when full length SEQ ID NO: 1 is used. The Specification teaches that the CD47 can be purchased and cell transfection with the CDX-CD47, CREKA-CD47 plasmid (paragraph [0198]). The specification teaches that two different peptides, a CDX peptide (FKESWREARGTRIERG (SEQ ID NO: 104)) for U87 targeting, and a CREKA for GL261 targeting, and a FLAG epitope, were inserted into the N-terminal of CD47, separately, and that the N-terminal of CD47 was localized to the external exosomal surface (FIG. 8B).(para [0189]). Moreover, “The addition of targeting peptide dramatically increased the CD47-exosome (Exo-T) uptake in U87 and GL261 cells, as well as translation of PTEN protein (FIG. 8C-F, FIG. 9, and FIG. 10A-D).” (paragraph [189]). This disclosure is not deemed to be descriptive of the complete structure of a representative number of polypeptide sequences encompassed by the instant claims as one of skill in the art cannot envision all the fragments of the transmembrane domain and extracellular domain of CD47 functionally able to enable expression of fusion proteins on secreted exosomes. The specification does not teach regions or domains of CD47 or the specific SEQ ID NO: 1 for that matter that are essential for the claimed activity. The specification describes five transmembrane domains within SEQ ID NO: 1 but does not describe which are essential for enabling exosome expression (Specification, [0081]). Further, the extracellular domains span the transmembrane domains and the specification fails to teach any fragment exclusively expressing the extracellular domain or exclusively expressing a transmembrane domain without their respective flanking transmembrane/extracellular domains (Specification, [0081]). Hence, there is no structure/function relationship taught at all for the amino acid sequence of SEQ ID NO: 1 and a heterologous targeting domain that is covalently linked (e.g, a CDX peptide (FKESWREARGTRIERG (SEQ ID NO: 104)) for U87 targeting, and a CREKA for GL261 targeting) that dramatically increased the CD47-exosome (Exo-T) uptake in U87 and GL261 cells. To the extent that a structure/function relationship can be gleaned from the instant specification, it is with respect to full length CD47 only and one polypeptide of 100% identity to SEQ ID NO: 1 where the N-terminal of CD47 is functionally linked to a heterologous targeting domain.
The written description requirement for a claimed genus 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 a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the inventor was in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. See Juno Therapeutics, Inc. v. Kite Pharma, Inc., 10 F.4th 1330, 1337, 2021 USPQ2d 893 (Fed. Cir. 2021). Further, A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that "only describe[d] one type of structurally similar antibodies" that "are not representative of the full variety or scope of the genus."). The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure "indicates that the patentee has invented species sufficient to constitute the gen[us]." See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004) ("[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated."). See MPEP 2163(II)(A)(3)(a)(ii).
In disclosing only a single CD47 polypeptide (SEQ ID NO: 1) where the N-terminal of CD47 is functionally linked to a heterologous targeting domain , applicant has not disclosed a representative number of species for the entire genus claimed because the genus claimed covers species in which the transmembrane domain (residues 142-162, 177-197, 208-228, 236-256, or 269-289 of SEQ ID NO: 1) has as many as 10 of its 105 amino acid residues, or 2 of its 20 amino acid residues depending on the fragment replaced with any amino acid (including bend-introducing residues like proline and residues containing large aliphatic side chains like tryptophan) and species in which an extracellular domain (residues 19-141, 198-207, or 257-268 of SEQ ID NO: 1) has as many as 12 of its 123 amino acid residues, 1 of its 10 amino acid residues, or 1.1 of its 11 amino acid residues depending on the fragment replaced with any amino acid (including bend-introducing residues like proline and residues containing large aliphatic side chains like tryptophan). A skilled artisan would understand that replacing all of these residues with proline would significantly impact the functional ability of the targeting protein to be expressed on secreted exosomes. Hence, the structure/function correlation of a polypeptide is unpredictable and a skilled artisan would recognize that the vast genus claimed encompasses species whose function would be hindered if not abolished by specific amino acid substitutions.
The skilled artisan understands that one nucleotide change in a DNA molecule or one amino acid change in the polypeptide encoded by the DNA molecule could result in loss of its biological activity as demonstrated in the generation of sickle-cell anemia wherein one specific amino acid mutation gives rise to the inherited disease (Voet et al., Biochemistry, John Wiley and Sons, 1990, p. 126-129). Further, the skilled artisan also understands that the significance of particular amino acids within a peptide cannot be predicted a priori but must be determined from case to case by painstaking experimental study (Rudinger, J., Peptide Hormones. Palgrave, London, 1976. 1-7. (Page 6, “Conclusions”)) and that it is not known whether there exists an algorithm for predicting the structure of a given protein from its amino acid sequence alone (Ngo, J. Thomas, Joe Marks, and Martin Karplus., The protein folding problem and tertiary structure prediction. Boston, MA: Birkhäuser Boston, 1994. 433-506. (page 492, second full paragraph)). The specification prophetically discloses that an undefined genus of 90% identity to a CD47 transmembrane domain or of 90% identity to amino acid positions 19-141, 198-207, or 257-268 of SEQ ID NO: 1 will have the function of exosome expression (Specification, [0082]). However, the specification is silent as to what portions of the CD47 polypeptide linked to a heterologous targeting domain are responsible for the functional property of exosome expression observed when full length SEQ ID NO: 1 is used. Thus, a skilled artisan would understand from the teachings of Voet, Rudinger, and Ngo that the results of changing any given amino acid within SEQ ID NO: 1 where the N-terminal of CD47 is functionally linked to a heterologous targeting domain would be unpredictable in relation to dramatically increasing the CD47-exosome (Exo-T) uptake in U87 and GL261 cells and that it would require significant experimentation to determine which variants of SEQ ID NO: 1 would still possess the desired function.
Response to Arguments
Applicant argues that because CD47 is a known protein at the time of filing, and because the claims are now directed to 90% identity which is higher than the 85% identity exemplified in the USPTO written description training materials circa 2008, the amended claim 1 satisfies the written description requirement (Remarks, at 10-11). This argument has been fully considered but has not been found persuasive for the following reasons.
First, the training materials Applicant references cannot be located and have not been provided by Applicant. In any event, the Examiner’s most recent guidance regarding archived 2008 materials is the following: “The archived training materials are outdated and should not be relied upon as reflecting the current state of the law regarding 35 U.S.C. [sections] 101 and 112.” See Clarification of Written Description Guidance For Claims Drawn to Antibodies and Status of 2008 Training Materials. The Examiner has complied with the most recent guidance on examining claims for satisfaction of the Written Description requirement of 35 U.S.C. 112(a) found in MPEP 2163. Accordingly, this argument is not found to be persuasive. In addition, Applicant’s amendments have further complicated the issues of written description for the pending claims (see rejection above).
Furthermore, it is noted that the instant claims are not merely directed to methods comprising a polypeptide with at least 90% sequence identity to the amino acid of SEQ ID NO:1. The instant claims are directed to an amino acid sequence set forth in SEQ ID NO: 1, and require fragments of SEQ ID NO:1 including extracellular domains that are functionally linked to a heterologous targeting domain. The Specification merely teaches one example of CD47 adapter polypeptide having the amino acid sequence of SEQ ID NO:47 where the N-terminal of CD47 is functionally linked to a heterologous targeting domain and wherein the transmembrane domain of the amino acid of SEQ ID NO:1 is incorporated in a membrane of said extracellular vesicle (e.g., dramatically increasing the CD47-exosome (Exo-T) uptake in U87 and GL261 cells) . There is no teaching regarding which 20 % of the amino acids will vary from SEQ ID NO: 1 when linked to a heterologous targeting domain to result in the required function. There are no functional characteristics disclosed for any polypeptide having 90% structural identity to SEQ ID NO: 1.
New Rejections in view of Applicant’s Amendments and Arguments
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 171-172 are newly 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.
Claims 171 and 172 are unclear insofar as they claim the method of claim 1 which is directed to a method of making an exosome while attempting to further claim steps directed to a method of using the exosomes produced by claim 1. This is unclear as it is unclear whether Applicant intends claims 171-172 to encompass a method of making or a method of using. For the purpose of compact prosecution, these claims are interpreted as encompassing the same claim scope as claim 1 from which they depend because claims 171-172 themselves impart no further structural limitations by the recitation of their steps, consequently, the products made through claim 1 and claims 171-172 are the same.
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 175-176 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 claimed invention. This is a new matter rejection.
The amendments to the claims added claims 175 and 176 which attempt to further specify “covalent” as either “direct” or “indirect” covalent linkage respectively. This is neither supported by the art or the specification. The MPEP teaches, “New or amended claims which introduce elements or limitations which are not supported by the as-filed disclosure violate the written description requirement. See, e.g., In re Lukach, 442 F.2d 967, 169 USPQ 795 (CCPA 1971) (subgenus range was not supported by generic disclosure and specific example within the subgenus range); In re Smith, 458 F.2d 1389, 1395, 173 USPQ 679, 683 (CCPA 1972) (a subgenus is not necessarily described by a genus encompassing it and a species upon which it reads). (see e.g. MPEP 2105).
In the instant case, “covalent” appears in the specification 28 times. In none of those recitations is “covalent” further specified as either direct or indirect. As stated above, a subgenus is not necessarily described by a genus encompassing it. The skilled artisan understands that peptide bonds, such as those that occur between amino acids, are covalent linkages. The skilled artisan does not typically further break the term “covalent” down to either indirect or direct when referencing linkages between amino acids. Accordingly, the skilled artisan would not conclude that Applicant was in possession of fusion peptides comprising both direct and indirect covalent linkages.
Other Relevant Prior Art
Pachuk et al. US2010/0323001, published 12/23/2010 (of record) = mRNA transfection of cells using electroporation.
Kalluri et al. US 2019/0117570, published 4/25/2019 (of record) = Electroporation of exosomes.
Chang et al. "3D nanochannel electroporation for high-throughput cell transfection with high uniformity and dosage control." Nanoscale 8.1 (2016): 243-252 (of record) = electroporation apparatus.
Yang et al. "Large-scale generation of functional mRNA-encapsulating exosomes via cellular nanoporation." Nature biomedical engineering 4.1 (2020): 69-83 (of record) = authors work.
Zhang, Ying, et al. "Recent advances in exosome-mediated nucleic acid delivery for cancer therapy." Journal of nanobiotechnology 20.1 (2022): 279. = Current state of the art for exosome-mediated cancer therapies.
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRENDAN THOMAS TINSLEY whose telephone number is (703)756-5906. The examiner can normally be reached Mon-Fri 8:00-5:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, MARIA G LEAVITT can be reached at 571-272-1085. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/BRENDAN THOMAS TINSLEY/Examiner, Art Unit 1634
/MARIA G LEAVITT/Supervisory Patent Examiner, Art Unit 1634