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 .
Claim Status
Claims 1-4, 6, 10-16, 25-30 and 36-37 are currently pending in this application.
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-4, 6 and 10-15, and the species of membrane protein NDST1 in the reply filed 5/1/26 is acknowledged. Claims 4, 6, 16, 25-30 and 36-37 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected subject matter, there being no allowable generic or linking claim. Claims 1-3 and 10-15 have been considered on the merits.
Priority
Acknowledgement is made of applicant’s claim for the benefit of the prior-filed applications US 63/301,233. The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosures of the prior-filed applications, fail to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. Entitlement to priority to Jan 20, 2022 does not apply to the subject matter of claims 1-4, 6 and 10-15 due to a lack of support for every membrane protein specifically recited in claim 1 or 6, therefore the earliest effective filing date of claims 1-4, 6 and 10-15 is Jan. 17, 2023 based on the filing date of PCT/US2023/010915.
Claim Interpretation
Regarding claim 1, the phrase “vesicle prepared from a mammalian cell line genetically modified to overexpress a membrane protein” is interpreted as a product-by-process limitation to the claimed composition. However, the recited process does not necessarily imply any additional structural limitation to the composition beyond the vesicles being derived from a mammalian cell type, e.g., whether synthetically formed or naturally secreted as extracellular vesicles or nanovesicles as in dependent claim 15. Furthermore, dependent claims 2-3 and 10-13 merely narrower the scope of this process of making. Note for patentability over the prior art purposes, product-by-process claims are treated outrightly as products, while for patent infringement purposes, product-by-process claims are treated exclusively as process claims. See Abbott v. Sandoz, 566 F.3d 1282 (Fed. Cir. 2009). While the recited process used in making the claimed product may comprise isolating vesicles from specifically recited cell types, there is no unrecited structural feature(s) clearly implied in the vesicles of these claims. A chemical composition and its properties are inseparable (see MPEP 2112.01). Further, “[w]hen the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990) (MPEP 2112(V)).
Regarding claims 11-13, the recited limitations to the process of making the product does not necessarily imply any additional structural limitation to the composition despite requiring the vesicles be derived from a specific mammalian cell type, e.g., HEK293, CHO, or stem cell (e.g., embryonic stem cell, primary stem cell, induced pluripotent stem cell, hematopoietic stem cell, neuronal stem cell, mesenchymal stem cell, muscle stem cell or skin stem cell).
In claim 1, the phrase “wherein the vesicles when administered to a subject reduces the levels of at least one proinflammatory cytokine in the subject” merely recites an intended use of the product generated by the claimed method; however this intended language is not interpreted as adding any implied structural limitation to the claimed product not expressly recited in the claim. Similarly, claim 14 merely narrows the scope of this intended use.
Claim 1 is interpreted as encompassing vesicles having any amount of NDST1 and regardless of whether the NDST1 is membrane bond and/or internal to the vesicle (see 112(b) rejection below).
The term “cell line” is not defined (in either the claims or instant specification) and is interpreted as being mutually exclusive with the term “primary cell” (i.e., a cell isolated freshly from a tissue of a subject) whereas a “cell line” is permanently established cell population propagated in laboratory, e.g., an immortal cell line. Note, the term “pharmaceutically acceptable carrier” is defined in the instant application as encompassing a diluent (e.g., saline), vehicle (e.g., buffered saline comprising serum albumin), excipient, salt, buffer or buffering agent, antioxidant, preservative, emulsifying agent, suspending agent, dispersing agent, solvent, filler, bulking agent, detergent, and/or adjuvant (e.g., a virosome or vector system) (see instant pg. 18).
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 1-3 and 10-15 are rejected under 35 U.S.C. 101 because the claimed invention is not directed to patent eligible subject matter. Based upon an analysis with respect to the claim as a whole, claims do not recite something significantly different than a judicial exception. The rationale for this determination is explained below.
The claims are interpreted as explained in a previous section.
Claims 1-3 and 10-15 are directed to a composition product comprising (1) mammalian cell vesicles comprising bifunctional heparan sulfate N-deacetylase/N-sulfotransferase 1 (NDST1) and (2) a pharmaceutically acceptable carrier (such as water), which can be made, e.g., by a process comprising a genetically modified mammalian cell line overexpressing NDST1. As defined in the instant specification, the term “bifunctional heparan sulfate N-deacetylase/N-sulfotransferase 1” encompasses naturally occurring proteins (e.g., UniProt Acc. No. P52848) (pg. 13, lines 16-25); and the term “vesicle” encompasses naturally secreted vesicles (i.e., extracellular vesicles) (pg. 3, lines 4-7; pg. 4, lines 1-3).
The prior art teaches of naturally occurring mammalian extracellular vesicles (EVs) comprising NDST1 in a composition comprising the pharmaceutical carrier water (Vesiclepedia (Vesiclepedia database, http://microvesicles.org/; last accessed 6/18/2026; N-deacetylase and N-sulfotransferase 1 or Ndst1; for example, extracellular vesicles from human mesenchymal stem cells, human cancer cells, human urine-derived cells, mouse cardiomyocytes or mouse melanoma cells. Thus, the claimed vesicle composition necessarily involves a product of nature.
It is only the recited structural limitations in the claims that are examined under 101 and not aspects such as how the claimed composition product is made or what the product is intended to be used for. In this case, only a composition comprising (1) mammalian cell vesicles comprising NDST1 and (2) a pharmaceutically acceptable carrier is examined with respect to its status as judicial exceptions. The phrases (1) “prepared from a mammalian cell line genetically modified to overexpress a membrane protein” and (2) “wherein the vesicles when administered to a subject reduces the levels of at least one proinflammatory cytokine in the subject” do not further limit the composition claimed as a product.
Regarding Step 2A, the claims encompass compositions using only nature-based products (e.g., mammalian vesicles and water) even if the vesicles are highly-purified/enriched compared to a natural state and/or in an in vitro aqueous carrier. In this regard, the claims encompass compositions existing in nature.
As interpreted in a previous section, claim 1 lacks any recitation of any structural feature(s) that would distinguish the claimed product beyond the implication that the vesicles may be isolated and placed in an in vitro composition related to pharmaceuticals, which encompasses natural carriers. There is no evidence in the instant application that the entire scope of the claimed product necessarily has any markedly different from certain naturally occurring extracellular vesicles. Thus, the claimed cell culture product is directed a “product of nature” exception. In re Roslin Institute (Edinburgh), 750 F.3d 1333, 1338-39 (Fed. Cir. 2014).
Regarding claim 15, there is no evidence that this claimed composition necessarily has any markedly different from certain naturally occurring compositions comprising extracellular vesicles nanovesicles or extracellular nanovesicles. Accordingly, the claimed invention of claim 15 is directed to an exception.
Thus, an examination of Step 2A prong 1 in the revised 101 guidance, with respect to the claimed invention, the answer is yes because the claimed invention comprises one or more naturally occurring products (judicial exceptions). In the instant case, these naturally occurring products are a plurality of vesicles any markedly different characteristic from certain naturally occurring mammalian cell vesicles.
When examining the claimed invention with regards to Step 2A prong 2, the answer is ‘no’ because the claimed invention does not integrate the judicial exception in the instant case into a practical application. Changing the purity and/or concentration of a natural product from that which exists in a nature does not necessarily integrate the mammalian cell vesicle comprising composition into a practical application (see October 2019 Patent Eligibility Guidance Update at Example 44: Denveric Acid, claim 1; Ass’n for Molecular Pathology v. Myriad Genetics, Inc., 569 U.S. 576 (2013) (isolated BRCA polynucleotides held ineligible)). In the instant case, if the vesicles are both removed away from cells and possibly increased in concentration without any recited alteration to the structure of said vesicles, this does not necessarily introduce any markedly different characteristic in the absence of evidence.
An examination of Step 2B, the answer is ‘no’ with respect to the claimed invention of claims 1-3 and 10-15. There are no other additional elements recited in the claims that would amount to significantly more than the judicial exception.
The only factors which can be examined under 101 in the claimed composition are those that are recited in the claims, i.e. a vesicle composition. How the vesicle composition was obtained and the knowledge of using them are not considered with respect to a such a composition claim, it is only the judicial exceptions themselves that are analyzed under 101 and in this case all of the components in the claimed composition are naturally-occurring products and thus qualifies as a judicial exception. Note, the fact that the claimed product may comprise in vitro isolated vesicles or a more concentrated form does not change the vesicles in a significant or meaningful way to amount to more than the judicial exception. Moreover, purifying exosomes away from naturally occurring biological samples is well-understood, routine, and conventional for use in increasing the purity and concentration of desired vesicles in an in vitro container. Similarly, culturing purified cells in vitro is well-understood, routine, and conventional for use in increasing the concentration of desired vesicles in an in vitro container. Because the claimed invention does not include any additional features that could add significantly more to the exceptions, the so called cell culture products claimed do not qualify as eligible subject matter, and should be rejected under 35 U.S.C. § 101.
Claim Rejections - 35 USC § 112(a), Written Description
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 1-3 and 10-15 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 and under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter. 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.
The claimed invention as a whole is not adequately described if the claims require essential or critical elements that are not adequately described in the specification and that is not conventional in the art as of applicant’s effective filing date. Possession may be shown by actual reduction to practice, clear depiction of the invention in a detailed drawing, or by describing the invention with sufficient relevant identifying characteristics such that a person skilled in the art would recognize that the inventor had possession of the claimed invention. Pfaff v. Wells Electronics, Inc., 48 USPQ2d 1641,1646 (1998).
In making a determination of whether the application complies with the written description requirement under 35 U.S.C. 112(a) or 35 U.S.C. 112, first paragraph, it is necessary to understand what Applicant is claiming and what Applicant has possession of. The elected invention of claim 1 is a composition comprising (1) vesicles derived from a mammalian cell(s) and comprising bifunctional heparan sulfate N-deacetylase/N-sulfotransferase 1 (NDST1) and (2) a pharmaceutically acceptable carrier; and “wherein the vesicles when administered to a subject reduces the levels of at least one proinflammatory cytokine in the subject.” Claims 11-13 further limit the composition as being somehow derived from a specifically recited subgenus of mammalian cell. Moreover, only dependent claim 14 further limits the claim 1 wherein clause recited above to specifically recited cytokines.
The prior art teaches that NDST1 has proinflammatory functions by generating N-sulfated glucosamine residues on heparan sulfate (HS) chains and thus is generally stimulating as to proinflammatory cytokine secretions, or at least exert diverse and unpredictable effects on different cytokines (see Collins and Troeberg (2018) at Fig. 1, pg. 82-84). Nowhere does the instant specification describe any example of a composition of claim 1 capable of reducing the levels of a single proinflammatory cytokine in the subject. This lack of description in view of contrary evidence in the prior art, is insufficient to establish possession. Therefore, the skilled artisan cannot envision any composition encompassed by claim 1 wherein the composition is capable, upon administration to a subject, of reducing the level of a proinflammatory cytokine in the subject. Claims 2-3 and 10-15 are included in this rejection for having the same deficiencies as claim 1.
The claimed invention as a whole is not adequately described if the claims require essential or critical elements that are not adequately described in the specification and that is not conventional in the art as of applicants effective filing date, such as structures/functions to (1) provide for the ability to reduce the level of a proinflammatory cytokine in a subject upon administration of the claimed composition to the subject.
Claim Rejections - 35 USC § 112(b)
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 1-3 and 10-15 are 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 pre-AIA the applicant regards as the invention.
Claim 1 recites the membrane protein has been “overexpressed” during the process used to make the claimed composition, which is a relative term. The term “over” as used is indefinite for not being anchored to any reference (e.g., a reference value or wild-type specimen) because neither the claim nor the specification provides a standard or means for determining a boundary for overexpression versus mere expression to inform the skilled artisan of the metes and bounds of this limitation regarding any vesicle composition derived therefrom. All membrane proteins are overexpressed compared to something else, if that something else is unlimited. If the scope of the structure of the vesicles in the claimed composition are to be limited, then such a limitation must be definite. Claim 1 was interpreted as encompassing vesicles having any amount of the NDST1 as any reference point for having more NDST1 than normal is indefinite. Claims 2-3 and 10-15 are included in this rejection for depending from indefinite claim 1.
Claim 1 recites the term “carrier” or “pharmaceutically acceptable carrier” which as defined by the instant application encompasses an adjuvant, such as an aluminum salt, poly-ICLC, 1018 ISS, Amplivax, AS15, BCG, CP-870,893, CpG7909, CyaA, dSLIM, GM-CSF, IC30, IC31, Imiquimod, ImuFact IMP321, IS Patch, ISS, ISCOMATRIX, JuvImmune, LipoVac, MF59, monophosphoryl lipid A, Montanide IMS 1312, Montanide ISA 206, Montanide ISA 50V, Montanide ISA-51, OK-432, OM-174, OM-197-MP-EC, ONTAK, PEPTEL, vector system, PLGA microparticle, resiquimod, SRL172, virosomes, virus-like particle, YF-17D, VEGF trap, R848, beta-glucan, Pam3Cys, acrylic or methacrylic polymer, or copolymer of maleic anhydride and Aquila's QS21 stimulon (pg. 18, lines 1-27). However the ordinary and customary meaning of “carrier” in the pharmaceutical formulary field is limited to excipients, i.e., inactive ingredients/substances; while adjuvants are defined as being immunologically active. If the applicant acts as her own lexicographer to redefine a term of a claim contrary to its ordinary meaning, the written description must clearly define the claim term and set forth the uncommon definition so as to put one reasonably skilled in the art on notice that the applicant intended to so redefine that claim term. Process Control Corp. v. HydReclaim Corp., 190 F.3d 1350, 1357, 52 USPQ2d 1029, 1033 (Fed. Cir. 1999). In the instant case, there is no such clear redefinition of “carrier” or “pharmaceutically acceptable carrier.” Furthermore, this carrier term is being used to encompass any adjuvant “vector system.” Thus, claim 1 is indefinite because the scope of the term pharmaceutically acceptable carrier is incoherent and unclear. Claims 2-3 and 10-15 are included in this rejection for depending from indefinite claim 1.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 14 is rejected 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.
The claims are interpreted as provided in a previous section.
Claim 14 is interpreted as an intended use limitation that does not limit the scope of claim 1 in absence of evidence to the contrary. Thus without more, claim 14 prima facie fails to further limit the subject matter of claim 1.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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 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 1-3 and 10-15 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Steenbeek (Steenbeek et al., EMBO J 37: e98357 (2018)).
The claims are interpreted as provided in a previous section.
Regarding claim 1, Steenbeek discloses a composition (extracellular vesicle composition derived from B16 cells) comprising mammalian cell line vesicles comprising NDST1 and a pharmaceutically acceptable carrier (water or PBS) (pg. 4, last para., to pg. end of 5; pg. 14, right col., para. 3-4; Suppl. Peptide Table at Q3UHN9, Q3UHN9-2, and Q3UHN9-3).
For purposes of applying prior art, intended language is not given patentable weight unless the intended language imparts an implied limitation to the method step(s). A recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. The phrases “wherein the vesicles when administered to a subject reduces the levels of at least one proinflammatory cytokine in the subject” is an intended use limitation, which does not contain any further structural limitations with respect to the claimed composition made by the active steps of the process recited in the claims (see MPEP §2114). Thus, claim 14 is anticipated for the same reasons set forth for claim 1 above (see 112(d) rejection above).
Regarding claims 2-3 and 10-13, there is no unrecited structural feature(s) clearly implied in the vesicles of these claims, such as distinguishing a vesicle from a mouse embryonic stem cell line, iPSC, or skin stem cell from ones from a B16 cell, especially as recited at a high generality of “prepared from” (i.e., somehow derived from). Furthermore regarding claims 10 and 12-13, Steenbeek discloses wherein the mammalian cell line (B16F1 or B16F10) is from a parental cell (B16), which was a primary cell isolated from a subject and from a parental cell line comprising skin cancer stem cells.
Therefore, claims 1-3 and 10-14 is each anticipated by Steenbeek for the same reasons set forth fully above for claim 1. To the extent any such characteristic is argued to be absent from the method taught by the prior art as laid out above, then the active methods steps as recited in the claims may lack sufficient written description to ensure the implied characteristic(s) would predictably be present (see 112(a) rejection above).
For the aforementioned reasons, Steenbeek anticipates the claimed invention.
Conclusion
No claim is allowed.
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 ERIC J ROGERS whose telephone number is (571)272-8338. The examiner can normally be reached Monday - Friday 9:00-6:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Tracy Vivlemore, can be reached on 571-272-2914. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ERIC J ROGERS/Examiner, Art Unit 1638
/Tracy Vivlemore/Supervisory Primary Examiner, Art Unit 1638
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