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 .
Detailed Action
This action is in response to the papers filed December 17, 2025.
Amendments
Applicant's response and amendments, filed December 17, 2025, to the prior Office Action are acknowledged.
Applicant has cancelled Claims 2 and 9, amended Claim 1, and withdrawn Claims 5-8, and 10-13, and added new claims, Claims 14-17.
Claims 1, 3-8, and 10-17 are pending.
Election/Restriction
Applicant's election without traverse of Group I, claims 1-4, directed to an extracellular vesicle comprising an exogenous therapeutic component, in Applicants’ response filed on March 22, 2024 is acknowledged.
Claims 1, 3-8, and 10-17 are pending.
Claims 5-8 and 10-13 are withdrawn from further consideration by the Examiner, pursuant to 37 CFR 1.142(b), as being drawn to non-elected inventions, there being no allowable generic or linking claim. Claims that were drawn to a non-elected invention would have been withdrawn, as being directed to a non-elected invention. Reinstatement of claims drawn to non-elected inventions will be withdrawn during prosecution.
Claims 1, 3-4, and 14-17 are under examination.
Priority
The present application is a 35 U.S.C. 371 national stage filing of International Application No. PCT/US2019/043172, filed July 24, 2019. Applicants’ claim for the benefit of prior-filed parent provisional application 62/702,882 filed on July 24, 2018 is acknowledged.
Thus, the earliest possible priority for the instant application is July 24, 2018.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
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.
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.
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.
1. The prior rejections of Claims 1 and 3-4 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, and 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, are withdrawn in light of Applicant’s amendments to Claim 1 to cancel recitation of “purified exosome product (PEP)” and “having their native spherical or spheroid structure”.
2. Claims 1, 3-4, and 14-17 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as failing to set forth 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 1 recites a composition comprising:
i) exosomes; and
ii) a heterologous therapeutic component.
Evidence that Claim 1 fail(s) to correspond in scope with that which the inventor or a joint inventor, or for pre-AIA applications the applicant regards as the invention can be found in the replies filed October 1, 2024 and December 17, 2025.
In the October 1, 2024 paper, the inventor or a joint inventor, or for pre-AIA applications the applicant has stated “these vesicles can be further enhanced by adding [heterologous therapeutic component] to the vesicle” (e.g. pg 6 of 16; citing specification pg 2, line 27 to pg 3, line 6; “extrcellular vesicles can be further enhanced with RNA…..transfection”), “transforming the exosome with the exogenous component augments….. that component within the exosomes” (e.g. pg 8 of 16), and “the exogenous therapeutic component provided in the PEP exosomes” and “the cargo is present” (e.g. pg 9 of 16).
In the December 17, 2025 paper, the inventor or a joint inventor, or for pre-AIA applications the applicant has stated “exosomes that include the heterologous therapeutic component” (e.g. pg 6 of 17) and “exosomes….before being subjected to a transformation procedure” and “exosomes…. amenable to transformation with a heterologous component” (e.g. pg 8 of 17).
These statements indicate that the invention is different from what is defined in the claim(s) because independent Claim 1 fails to recite that the exosomes are transformed to comprise the heterologous therapeutic component as a cargo. Rather, the claim is directed to a compositions comprising exosomes lacking the heterologous therapeutic component as a cargo in the presence of a heterologous therapeutic component external and not associated with the exosomes.
The Examiner suggests amending Claim 1 to recite the exosomes comprise the heterologous therapeutic component.
Claim 1 recites the process step of “reconstituting the exosomes in a liquid comprising a detergent from a lyophilized composition comprising [the exosomes]”.
Evidence that Claim 1 fail(s) to correspond in scope with that which the inventor or a joint inventor, or for pre-AIA applications the applicant regards as the invention can be found in the replies filed December 17, 2025.
In the December 17, 2025 paper, the inventor or a joint inventor, or for pre-AIA applications the applicant has stated that Claim 1 incorporates the lyophilization occurs in the presence of a detergent (e.g. pg 9 of 17).
These statements indicate that the invention is different from what is defined in the claim(s) because while it is clear that the amended Claim 1 step of reconstituting a lyophilized composition comprising exosomes is in a liquid comprising a detergent, instant Claim 1 fails to recite that the step of lyophilizing a composition comprising exosomes occurs in the presence of a detergent.
Dependent claims are included in the basis of the rejection because they do not correct the primary deficiencies of the independent claim(s).
3. Claims 1, 3-4, and 14-17 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites the limitation “the exosomes” (lines 10 and 12, respectively). There is insufficient antecedent basis for this limitation in the claim because it is unclear if “the exosomes” refers back to the exosomes before or after they are modified to comprise the heterologous therapeutic component.
A claim may be rendered indefinite by reference to an object that is variable. (MPEP §2173.05(b)).
If there are multiple different exosomes that are to be referenced in the Product-by-Process limitations, then the claim may be indefinite because it is unclear which exosome is to be present in the Product-by-Process limitations in order to determine infringement.
The instant claims as a whole do not apprise one of ordinary skill in the art of its scope and, therefore, does not serve the notice function required by 35 U.S.C. 112, second paragraph, by providing clear warning to others as to what constitutes infringement of the patent.
Dependent claims are included in the basis of the rejection because they do not correct the primary deficiencies of the independent claim(s).
4. Claims 1, 3-4, and 14-17 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Applicant has amended Claim 1, and newly presented Claims 14-17, to recite Product-by-Process limitations, per the terminal ‘wherein’ clause, which renders the claims indefinite as being incomplete for omitting essential steps, such omission amounting to a gap between the steps. See MPEP § 2172.01. The omitted steps are: transformation of the exosomes to comprise the heterologous therapeutic component.
The instant claims as a whole do not apprise one of ordinary skill in the art of its scope and, therefore, does not serve the notice function required by 35 U.S.C. 112, second paragraph, by providing clear warning to others as to what constitutes infringement of the patent.
Dependent claims are included in the basis of the rejection because they do not correct the primary deficiencies of the independent claim(s).
5. Claims 1, 3-4, and 14-17 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The term “residual starting material protein” in Claim 1 is a relative term which renders the claim indefinite. The term “residual starting material protein” 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.
The specification is silent to “residual starting material protein”, nor “residual, nor “starting”. The term “material” is disclosed in the context of the “heterologous materials” that are introduced into the exosomes via transformation (e.g. pg 2, Figure 1 legend).
However, Applicant argues support for this limitation is found in the specification (pg 11, lines 4-7), referring to Example 1 in which the purified exosomes are reconstituted in a solution comprising heparin sulfate (pg 11, line 3). While lines 5-7 disclose a DNA encoding a reporter gene protein luciferase that is to be electroporated into the exosomes, the luciferase protein itself is not present, and thus cannot be the “residual starting material protein”.
The specification Example 1 refers back to WO 19/118817 (e.g. pg 11, exosomes prepared as previously described in WO 19/118817).
However, WO 19/118817 discloses “reconstituted” in the context of different exosome preparations, for example:
i) simply formulating the exosomes with a pharmaceutically acceptable carrier (e.g. pg 12, lines 5-6);
ii) solubilizing an exosome product (e.g. pg 14, line 6);
iii) solubilizing a dried exosome product (e.g. pg 14, line 7);
iv) exosomes sorted via affinity separation, magnetic bead separation or flow separation based on the presence or absence of a surface marker (pg 19, lines 21-22);
v) exosomes isolated using ultracentrifugation and/or tangential flow filtration (e.g. pg 21, lines 1-2); and
vi) the exosome product is modified to comprise one or more of a genus of structurally different ingredients, e.g. collagen, thrombin, gelatin, alginate, hyaluronic acid (e.g. pg 13, lines 26-29), or PLGA (e.g. pg 14, line 18).
Example 1 of instant application fails to disclose with particularity and specificity the referenced exosome composition of WO 19/118817 that is being reconstituted with sterile water and heparin sulfate in the instant specification.
There is insufficient antecedent basis for this limitation in the claim because it is unclear to which protein the Product-by-Process limitation refers back to.
A claim may be rendered indefinite by reference to an object that is variable. (MPEP §2173.05(b)).
If there are multiple reference proteins from which “starting material protein” is to be determined, yet each yields a different result, to wit, the heterologous therapeutic polypeptide or some other source of protein, then the claim may be indefinite because it is unclear which protein is to be referenced in order to determine infringement.
The instant claims as a whole do not apprise one of ordinary skill in the art of its scope and, therefore, does not serve the notice function required by 35 U.S.C. 112, second paragraph, by providing clear warning to others as to what constitutes infringement of the patent.
Dependent claims are included in the basis of the rejection because they do not correct the primary deficiencies of the independent claim(s).
6. Claims 15-16 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 15 recites wherein 95% of the exosomes have a diameter that falls within a distribution range of 100nm.
Claim 16 recites wherein 90% of the exosomes have a diameter that falls within a distribution range of 60nm.
As a first matter, where applicant acts as his or her own lexicographer to specifically define a term of a claim contrary to its ordinary meaning, the written description must clearly redefine 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). The phrases “distribution range of 100nm” and “distribution range of 60nm” are indefinite because the specification does not clearly redefine the term.
Instant value 100nm is not a range. It is a single value.
Instant value 60nm is not a range. It is a single value.
As a second matter, while Example 1 of instant specification refers back to WO 19/118817 (e.g. pg 11, exosomes prepared as previously described in WO 19/118817), WO 19/118817 discloses several different distribution ranges that encompass the 100nm value (e.g. Figure 14), ranges from 0-600nm, 0-300nm, or 100-200nm.
A claim may be rendered indefinite by reference to an object that is variable. (MPEP §2173.05(b)).
If there are multiple reference distribution ranges from which “95% of the exosomes have a diameter that falls within” and/or “90% of the exosomes have a diameter that falls within” is to be determined, then the claim may be indefinite because it is unclear which distribution range is to be referenced in order to determine infringement.
The instant claims as a whole do not apprise one of ordinary skill in the art of its scope and, therefore, does not serve the notice function required by 35 U.S.C. 112, second paragraph, by providing clear warning to others as to what constitutes infringement of the patent.
7. Claims 14-17 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.
Claim 14 recites the step of freezing material comprising cells comprising the exosomes under conditions effective to disrupt the cells but not disrupt the exosomes. The claim suffers from a gap in the method step “under conditions effective”, recited at a high level of generality, in order to necessarily and predictably achieve the functional property/method result “disrupt the cells but not disrupt the exosomes”.
Claim 15 recites wherein the preparation process step(s) produce a population of exosomes in which 95% of the exosomes have a diameter that falls within a distribution range of 100nm. The claim suffers from a gap in the method step “are prepared produces”, recited at a high level of generality, in order to necessarily and predictably achieve the functional property/method result “95% of the exosomes have a diameter that falls within a distribution range of 100nm”.
Claim 16 recites wherein the preparation process step(s) produce a population of exosomes in which 90% of the exosomes have a diameter that falls within a distribution range of 60nm. The claim suffers from a gap in the method step “are prepared produces”, recited at a high level of generality, in order to necessarily and predictably achieve the functional property/method result “90% of the exosomes have a diameter that falls within a distribution range of 60nm”.
Claim 17 recites wherein the lyophilized composition has a shelf life of up to four years without refrigeration. The claim suffers from a gap in the method step/functional property nexus for failing to recite the method step that necessarily and predictably achieves the functional property/method result of the lyophilized composition has a shelf life of up to four years without refrigeration.
Without a correlation between structure and function, the claim does little more than define the claimed invention by function. That is not sufficient to satisfy the written description requirement. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406 (“definition by function ... does not suffice to define the genus because it is only an indication of what the gene does, rather than what it is’).
In analyzing whether the written description requirement is met for genus claims, it is first determined whether a representative number of species have been described by their complete structure. To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof. The disclosure of a single species is rarely, if ever, sufficient to describe a broad genus, particularly when the specification fails to describe the features of that genus, even in passing. (see In re Shokal 113USPQ283(CCPA1957); Purdue Pharma L.P. vs Faulding Inc. 56 USPQ2nd 1481 (CAFC 2000).
The court explained that “reading a claim in light of the specification, to thereby interpret limitations explicitly recited in the claim, is a quite different thing from ‘reading limitations of the specification into a claim,’ to thereby narrow the scope of the claim by implicitly adding disclosed limitations which have no express basis in the claim.” The court found that applicant was advocating the latter, i.e., the impermissible importation of subject matter from the specification into the claim.). See also In re Morris, 127 F.3d 1048, 1054-55, 44 USPQ2d 1023, 1027-28 (Fed. Cir. 1997).
The Examiner incorporates herein the above 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, rejections.
Applicant argues that support for these limitations are found in the instant specification, pg 11, lines 4-7.
The specification Example 1 refers back to WO 19/118817 (e.g. pg 11, exosomes prepared as previously described in WO 19/118817).
United States Court of Appeals for the Federal Circuit, Regents of the University of Minnesota v. Gilead Sciences, Inc (Case 21-2168; decided March 6, 2023).
Written description of a broad genus requires description not only of the outer limits of the genus but also of either a representative number of members of the genus or structural features common to the members of the genus, in either case with enough precision that a relevant artisan can visualize or recognize the members of the genus. See Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1350−52 (Fed. Cir. 2010) (en banc). A broad outline of a genus’s perimeter is insufficient. See id.
Original disclosure may not be relied upon unless it “constitute[s] a full, clear, concise and exact description” of the invention claimed in the patent to one of ordinary skill. In re Wertheim, 646 F.2d 527, 538–39 (CCPA 1981).
For genus claims, which are present here, we have looked for blaze marks within the disclosure that guide attention to the claimed species or subgenus. In re Ruschig, 379 F.2d 990, 994–95 (CCPA 1967); Fujikawa v. Wattana-sin, 93 F.3d 1559, 1571 (Fed. Cir. 1996); see also Purdue Pharma L.P. v. Faulding Inc., 230 F.3d 1320, 1326–27 (Fed. Cir. 2000).
Following this maze-like path, each step providing multiple alternative paths, is not a written description of what might have been described if each of the optional steps had been set forth as the only option. This argument calls to mind what Yogi Berra, the Yankee catcher, was reported to have said: “when one comes to a fork in the road, take it.” That comment was notable because of its indeterminacy, its lack of direction. Similarly, here, all those optional choices do not define the intended result of the instant combination of specific method step parameters.
Clearly, however, just because a moiety is listed as one possible choice for one position does not mean there is ipsis verbis support for every species or sub-genus that chooses that moiety. Were this the case, a “laundry list” disclosure of every possible moiety for every possible position would constitute a written description of every species in the genus. This cannot be because such a disclosure would not “reasonably lead” those skilled in the art to any particular species.
Indeed, the listings of possibilities are so long, and so interwoven, that it is quite unclear how many compounds actually fall within the described genera and subgenera.
As explained by the Board, “[t]hese blaze marks must be clear because ‘it is easy to bypass a tree in the forest, even one that lies close to the trail.’” Decision at *10 (citing Fujikawa, 93 F.3d at 1571).
The Board concluded that, “[i]n this case, we find the point at which one must leave the trail to find the tree is not well marked in [WO 19/118817]. Thus, [WO 19/118817] do not provide sufficient written description support for the sub-genus of challenged claim 1.” Decision at *10.
However, WO 19/118817 discloses “reconstituted” in the context of different exosome preparations, for example:
i) simply formulating the exosomes with a pharmaceutically acceptable carrier (e.g. pg 12, lines 5-6);
ii) solubilizing an exosome product (e.g. pg 14, line 6);
iii) solubilizing a dried exosome product (e.g. pg 14, line 7);
iv) exosomes sorted via affinity separation, magnetic bead separation or flow separation based on the presence or absence of a surface marker (pg 19, lines 21-22);
v) exosomes isolated using ultracentrifugation and/or tangential flow filtration (e.g. pg 21, lines 1-2); and
vi) the exosome product is modified to comprise one or more of a genus of structurally different ingredients, e.g. collagen, thrombin, gelatin, alginate, hyaluronic acid (e.g. pg 13, lines 26-29), or PLGA (e.g. pg 14, line 18).
Example 1 of instant application fails to disclose with particularity and specificity the referenced exosome composition of WO 19/118817 that is being reconstituted with sterile water and heparin sulfate in the instant specification.
Instant value 100nm is not a range. It is a single value.
Instant value 60nm is not a range. It is a single value.
WO 19/118817 discloses several different distribution ranges that encompass the 100nm value (e.g. Figure 14), ranges from 0-600nm, 0-300nm, or 100-200nm.
The claimed “lyophilized composition is recited at a high level of generality, and encompasses an enormous genus of structurally different exosome compositions, per WO 19/118817, including:
i) simply formulating the exosomes with a pharmaceutically acceptable carrier (e.g. pg 12, lines 5-6);
ii) solubilizing an exosome product (e.g. pg 14, line 6);
iii) solubilizing a dried exosome product (e.g. pg 14, line 7);
iv) exosomes sorted via affinity separation, magnetic bead separation or flow separation based on the presence or absence of a surface marker (pg 19, lines 21-22);
v) exosomes isolated using ultracentrifugation and/or tangential flow filtration (e.g. pg 21, lines 1-2); and
vi) the exosome product is modified to comprise one or more of a genus of structurally different ingredients, e.g. collagen, thrombin, gelatin, alginate, hyaluronic acid (e.g. pg 13, lines 26-29), or PLGA (e.g. pg 14, line 18).
WO 19/118817 discloses an enormously broad genus of process step temperatures [parameter 1], freezing rate steps [parameter 2], and vacuum pressures [parameter 3] by which to generate a lyophilized product (e.g. pg 8, line 10-pg 9, line 24), whereby the process may further comprise additional drying steps [parameter 4] and/or terminal temperature changes [parameter 5] (e.g. pg 9, lines 25-pg 10, line 21).
Instant claims fail to recite, and the specifications of instant application and WO 19/118817 fail to disclose, the nexus between the process step(s) parameters 1, 2, 3, 4, and 5 above, individually and/or in combinations and/or subcombinations thereof, that necessarily and predictably achieve the recited functional property of “the lyophilized composition has a shelf life of up to four years without refrigeration” , for example.
Instant claims fail to recite, and the specifications of instant application and WO 19/118817 fail to disclose, the nexus between:
the process step(s) that don’t disrupt the cells and don’t disrupt the exosomes, as opposed to
the process step(s) that disrupt the cells and disrupt the exosomes, as opposed to
necessarily and predictably achieving the recited functional property of “disrupt the cells but not disrupt the exosomes”, for example.
Instant claims fail to recite, and the specifications of instant application and WO 19/118817 fail to disclose, the nexus between:
the process step(s) that don’t yield at least 95% of the exosomes having a diameter that falls within a distribution range of 100nm, as opposed to
the process step(s) that necessarily and predictably yield at least 95% of the exosomes having a diameter that falls within a distribution range of 100nm, for example.
Instant claims fail to recite, and the specifications of instant application and WO 19/118817 fail to disclose, the nexus between:
the process step(s) that don’t yield at least 90% of the exosomes having a diameter that falls within a distribution range of 60nm, as opposed to
the process step(s) that necessarily and predictably yield at least 90% of the exosomes having a diameter that falls within a distribution range of 60nm, for example.
Instant claims fail to recite, and the specifications of instant application and WO 19/118817 fail to disclose, the nexus between:
the process step(s) that don’t yield at least 95% of the exosomes having a diameter that falls within a distribution range of 100nm, of which at least 90% of said exosomes have a diameter that falls within a distribution range of 60nm, as opposed to
the process step(s) that necessarily and predictably yield at least 95% of the exosomes having a diameter that falls within a distribution range of 100nm of which at least 90% of said exosomes have a diameter that falls within a distribution range of 60nm, for example.
While WO 19/118817 does disclose “the purified exosome product has a shelf life of at least six months but as long as four years without refrigeration” (e.g. pg 14, lines 2-3), such is devoid of the process steps that is/are necessary and sufficient to achieve the functional properties.
The disclosure of WO 19/118817 fails to provide ipsis verbis support nor sufficient blaze marks to guide the skilled artisan to the instant claims.
Thus, for the reasons outlined above, it is concluded that the claims do not meet the requirements for written description under 35 U.S.C. 112, first paragraph.
MPEP 2163 - 35 U.S.C. 112(a) and the first paragraph of pre-AIA 35 U.S.C. 112 require that the “specification shall contain a written description of the invention ....” This requirement is separate and distinct from the enablement requirement. Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1340, 94 USPQ2d 1161, 1167 (Fed. Cir. 2010) (en banc)
8. Claims 14-17 are 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.
Claims 14-17 recite Product-by-Process limitations.
However, Claim 1 is directed to a product, to wit, “A composition comprising” an exosome and a heterologous therapeutic component.
Claim 1 is not directed to a method of making a product.
The recitation of a process limitations in Claims 1 and 14-17 is/are not viewed as positively limiting the claimed product absent a showing that the process of making recited in Claims 1 and 14-17 imparts a novel or unexpected property to the claimed product of exosomes comprising a heterologous therapeutic component as it is assumed that equivalent products are obtainable by multiple routes. The burden is placed upon the applicants to establish a patentable distinction between the claimed and referenced products. The method in which the exosomes comprising a heterologous therapeutic component were produced is immaterial to their patentability.
Applicant fails to provide objective evidence as to how the exosomes produced by the instantly recited process step(s) recited in Claims 14, 15, 16, and/or 17, individually and/or in combination and/or subcombination(s) thereof, is/are materially, structurally, and/or functionally different from the claimed exosome product produced by the process step(s) recited in Claim 1.
Dependent Claims 14, 15, 16, and/or 17 fail to recite a structural change to the exosome composition of Claim 1.
The claims fail to recite, and the specification fails to disclose, a first composition comprising an exosome and a heterologous therapeutic component that is/was not produced by the process step(s) recited in Claim 17 that is/are materially, structurally, and/or functionally different from a second composition comprising an exosome and a heterologous therapeutic component that is/was produced by the process step(s) recited in Claim 17.
Rather, as discussed above, while WO 19/118817 does disclose “the purified exosome product has a shelf life of at least six months but as long as four years without refrigeration” (e.g. pg 14, lines 2-3), such is devoid of the process steps that is/are necessary and sufficient to achieve the functional properties.
The claims fail to recite, and the specification fails to disclose, a first composition comprising an exosome and a heterologous therapeutic component that is/was not produced by the process step(s) recited in Claims 15 and/or 16 that is/are materially, structurally, and/or functionally different from a second composition comprising an exosome and a heterologous therapeutic component that is/was produced by the process step(s) recited in Claims 15 and/or 16.
Instant claims fail to recite, and the specifications of instant application and WO 19/118817 fail to disclose, the nexus between:
the process step(s) that don’t disrupt the cells and don’t disrupt the exosomes, as opposed to
the process step(s) that disrupt the cells and disrupt the exosomes, as opposed to
necessarily and predictably achieving the recited functional property of “disrupt the cells but not disrupt the exosomes”, for example.
Instant claims fail to recite, and the specifications of instant application and WO 19/118817 fail to disclose, the nexus between:
the process step(s) that don’t yield at least 95% of the exosomes having a diameter that falls within a distribution range of 100nm, as opposed to
the process step(s) that necessarily and predictably yield at least 95% of the exosomes having a diameter that falls within a distribution range of 100nm, for example.
Instant claims fail to recite, and the specifications of instant application and WO 19/118817 fail to disclose, the nexus between:
the process step(s) that don’t yield at least 90% of the exosomes having a diameter that falls within a distribution range of 60nm, as opposed to
the process step(s) that necessarily and predictably yield at least 90% of the exosomes having a diameter that falls within a distribution range of 60nm, for example.
Instant claims fail to recite, and the specifications of instant application and WO 19/118817 fail to disclose, the nexus between:
the process step(s) that don’t yield at least 95% of the exosomes having a diameter that falls within a distribution range of 100nm, of which at least 90% of said exosomes have a diameter that falls within a distribution range of 60nm, as opposed to
the process step(s) that necessarily and predictably yield at least 95% of the exosomes having a diameter that falls within a distribution range of 100nm of which at least 90% of said exosomes have a diameter that falls within a distribution range of 60nm, for example.
The claims fail to recite, and the specification fails to disclose, a first composition comprising an exosome and a heterologous therapeutic component that is/was not produced by the process step(s) recited in Claim 14 that is/are materially, structurally, and/or functionally different from a second composition comprising an exosome and a heterologous therapeutic component that is/was produced by the process step(s) recited in Claim 14.
As discussed above, the claimed lyophilized composition is recited at a high level of generality, and encompasses an enormous genus of structurally different exosome compositions, per WO 19/118817, including:
i) simply formulating the exosomes with a pharmaceutically acceptable carrier (e.g. pg 12, lines 5-6);
ii) solubilizing an exosome product (e.g. pg 14, line 6);
iii) solubilizing a dried exosome product (e.g. pg 14, line 7);
iv) exosomes sorted via affinity separation, magnetic bead separation or flow separation based on the presence or absence of a surface marker (pg 19, lines 21-22);
v) exosomes isolated using ultracentrifugation and/or tangential flow filtration (e.g. pg 21, lines 1-2); and
vi) the exosome product is modified to comprise one or more of a genus of structurally different ingredients, e.g. collagen, thrombin, gelatin, alginate, hyaluronic acid (e.g. pg 13, lines 26-29), or PLGA (e.g. pg 14, line 18).
WO 19/118817 discloses an enormously broad genus of process step temperatures [parameter 1], freezing rate steps [parameter 2], and vacuum pressures [parameter 3] by which to generate a lyophilized product (e.g. pg 8, line 10-pg 9, line 24), whereby the process may further comprise additional drying steps [parameter 4] and/or terminal temperature changes [parameter 5] (e.g. pg 9, lines 25-pg 10, line 21).
See also discussions above per 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, and 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, rejections.
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.
9. Claims 1, 3-4, and 14-17 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Seow et al (U.S. 2013/0053426; of record).
With respect to Claim 1, Seow et al disclosed exosomes loaded with genetic material comprising nucleic acids for gene therapy and gene silencing (e.g. [0006]), wherein said exosomes are purified (e.g. [0092], “to purify the exosomes”; [0122], “then purified the exosomes”).
Seow et al successfully demonstrated the ability to introduce a heterologous therapeutic molecule into exosomes, e.g. transfecting the host cell with a nucleic acid expressing said therapeutic molecule, or electroporating said exosome (e.g. [0017-18, 90, 92]).
Seow et al disclosed wherein the exosomes have a diameter between 30nm and 100nm, or as large as 200nm (e.g. [0025]), with a size distribution peaking at 80nm (e.g. [0077]).
The recitation of a process limitation in Claims 1 and 14-17 is/are not viewed as positively limiting the claimed product absent a showing that the process of making recited in Claims 1 and 14-17 imparts a novel or unexpected property to the claimed product of exosomes comprising a heterologous therapeutic component as it is assumed that equivalent products are obtainable by multiple routes. The burden is placed upon the applicants to establish a patentable distinction between the claimed and referenced products. The method in which the exosomes comprising a heterologous therapeutic component were produced is immaterial to their patentability.
"Even though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 227 USPQ 964, 966 (Fed. Cir. 1985). See also MPEP §2113.
See also discussions above per the 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, and 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, rejections.
With respect to Claim 3, Seow et al disclosed examples of heterologous nucleic acids such as plasmid DNA and RNAi molecules (paragraphs [0033], [0037]). The nucleic acids are considered to be “native”, in that they are not required to be chemically modified, as per instant specification (pg 4, lines 15-16). Seow et al disclosed, for example, a working example of transfecting or electroporating exosomes with a chemically unmodified plasmid [0112-113].
With respect to Claim 4, Seow et al disclosed the heterologous nucleic acids for gene therapy include treatment of hemophilia B, cystic fibrosis or spinal muscular atrophy [0035], and thus the ordinary artisan would have reasonably inferred the gene therapy nucleic acid to encode a therapeutic protein such as Factor IX, CFTR, or SMN-1.
Thus, Seow et al anticipate the claims.
10. Claims 1, 3-4, and 14-17 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Wood et al (U.S. 2014/0348904; of record).
With respect to Claim 1, Wood disclosed cells for production of exosomes that are transfected with a polynucleotide construct encoding a fusion protein such that exosomes produced by the cells target the desired tissue/cell ([0075]), wherein said exosomes are purified (e.g. [0025], “exosome preparation that has already been isolated from cells”).
Wood et al successfully demonstrated the ability to introduce a heterologous therapeutic molecule into exosomes, e.g. transfecting the host cell with a nucleic acid expressing said therapeutic molecule (e.g. [0075]; Exampled 1-2), or electroporating said exosome (e.g. [0040]; Example 2).
Wood et al disclosed wherein the exosomes have a diameter between 30nm and 100nm, or as large as 200nm (e.g. [0017]).
The recitation of a process limitation in Claims 1 and 14-17 is/are not viewed as positively limiting the claimed product absent a showing that the process of making recited in Claims 1 and 14-17 imparts a novel or unexpected property to the claimed product of exosomes comprising a heterologous therapeutic component as it is assumed that equivalent products are obtainable by multiple routes. The burden is placed upon the applicants to establish a patentable distinction between the claimed and referenced products. The method in which the exosomes comprising a heterologous therapeutic component were produced is immaterial to their patentability.
"Even though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 227 USPQ 964, 966 (Fed. Cir. 1985). See also MPEP §2113.
See also discussions above per the 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, and 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, rejections.
With respect to Claim 3, Wood et al disclosed examples of heterologous nucleic acids such as plasmid DNA and RNAi molecules ([0025]). The nucleic acids are considered to be “native”, in that they are not required to be chemically modified, as per instant specification (pg 4, lines 15-16). Wood et al disclosed, for example, a working example of exosomes loaded with a chemically unmodified siRNA (Example 2, [0094-95]).
With respect to Claim 4, Wood et al disclosed the heterologous nucleic acids for gene therapy include treatment of hemophilia B, cystic fibrosis or spinal muscular atrophy [0030], and thus the ordinary artisan would have reasonably inferred the gene therapy nucleic acid to encode a therapeutic protein such as Factor IX, CFTR, or SMN-1.
Thus, Wood et al anticipate the claims.
11. Claims 1, 3-4, and 14-17 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Larocca et al., (U.S. Pub 2016/010368; of record).
With respect to Claim 1, Larocca et al disclosed exosomes derived from progenitor cells (paragraph [0002]), comprising therapeutic molecules such as nucleic acids, proteins, peptides, small molecules such as drugs and the like ([0127]), wherein the exosomes are purified (e.g. [0244], “The purified exosomes”; [0249], “exosome particles in a purified preparation of exosomes”).
Larocca et al disclosed the ability to introduce a heterologous therapeutic molecule into exosomes, e.g. transfecting the host cell with a nucleic acid expressing said therapeutic molecule (e.g. [0050-52]).
Larocca et al disclosed wherein the exosomes have a diameter between 80nm and 110nm, with a predominant peak around 85-91nm (e.g. [0226]).
The recitation of a process limitation in Claims 1 and 14-17 is/are not viewed as positively limiting the claimed product absent a showing that the process of making recited in Claims 1 and 14-17 imparts a novel or unexpected property to the claimed product of exosomes comprising a heterologous therapeutic component as it is assumed that equivalent products are obtainable by multiple routes. The burden is placed upon the applicants to establish a patentable distinction between the claimed and referenced products. The method in which the exosomes comprising a heterologous therapeutic component were produced is immaterial to their patentability.
"Even though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 227 USPQ 964, 966 (Fed. Cir. 1985). See also MPEP §2113.
See also discussions above per the 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, and 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, rejections.
With respect to Claim 3, Larocca et al disclosed exosomes comprising therapeutic molecules such as small molecules, nucleic acids such as DNA, RNA, include mRNA and miRNA ([0127];[0128]; [0146]). The nucleic acids are considered to be “native”, in that they are not required to be chemically modified, as per instant specification (pg 4, lines 15-16).
With respect to Claim 4, Larocca et al disclosed exosomes comprising therapeutic nucleic acid molecules such as mRNA, whereby those of ordinary skill in the art immediately recognize mRNA to encode peptides or proteins.
Thus, Larocca et al anticipate the claims.
12. Claims 1, 3, and 14-17 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Law et al (U.S. 2017/0252379; of record).
With respect to Claim 1, Law et al disclosed compositions comprising placenta-derived adherent cell exosomes ([0003, 35]) comprising one or more nucleic acids comprising a small interfering RNA (siRNA) or an miRNA or one or more gene-modifying components, e.g. gRNA ([0031]-[0032]) loaded into said exosomes (e.g. [0247]), whereby said exosomes are purified (e.g. [0260], “The purified exosomes”; Example 3).
Law et al disclosed the ability to introduce a heterologous therapeutic molecule into exosomes e.g. by electroporation of the exosomes (e.g. [0029]).
Law et al disclosed wherein the exosomes have a diameter between 50nm and 200nm, with a predominant peak around 108-116nm (e.g. Figure 2B) or a diameter between 50-150nm or 70-150nm (e.g. [0182, 205]).
The recitation of a process limitation in Claims 1 and 14-17 is/are not viewed as positively limiting the claimed product absent a showing that the process of making recited in Claims 1 and 14-17 imparts a novel or unexpected property to the claimed product of exosomes comprising a heterologous therapeutic component as it is assumed that equivalent products are obtainable by multiple routes. The burden is placed upon the applicants to establish a patentable distinction between the claimed and referenced products. The method in which the exosomes comprising a heterologous therapeutic component were produced is immaterial to their patentability.
"Even though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 227 USPQ 964, 966 (Fed. Cir. 1985). See also MPEP §2113.
See also discussions above per the 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, and 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, rejections.
With respect to Claim 3, Law et al disclosed that “e.g., pharmaceutical agent, loaded into the placenta-derived adherent cell exosomes described herein comprises one or more nucleic acids. In specific embodiments, the one or more nucleic acids comprise a siRNA or a miRNA” ([0033]). The nucleic acids are considered to be “native”, in that they are not required to be chemically modified, as per instant specification (pg 4, lines 15-16).
Thus, Law et al anticipate the claims.
Response to Arguments
Applicant argues that the none of Seow, Wood, Larocca, or Law teach/disclose the Product-by-Process steps.
Applicant’s argument(s) has been fully considered, but is not persuasive. The recitation of a process limitation in Claims 1 and 14-17 is/are not viewed as positively limiting the claimed product absent a showing that the process of making recited in Claims 1 and 14-17 imparts a novel or unexpected property to the claimed product of exosomes comprising a heterologous therapeutic component as it is assumed that equivalent products are obtainable by multiple routes. The burden is placed upon the applicants to establish a patentable distinction between the claimed and referenced products. The method in which the exosomes comprising a heterologous therapeutic component were produced is immaterial to their patentability.
"Even though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 227 USPQ 964, 966 (Fed. Cir. 1985). See also MPEP §2113.
See also discussions above per the 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, and 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, rejections.
Applicant fails to provide objective evidence as to how the exosomes produced by the instantly recited process steps is/are materially, structurally, and/or functionally different from the prior art exosomes modified to comprise a heterologous therapeutic component.
Applicant argues that the lyophilization occurs in the presence of a detergent.
Applicant’s argument(s) has been fully considered, but is not persuasive. While it is clear that the amended Claim 1 step of reconstituting a lyophilized composition comprising exosomes is in a liquid comprising a detergent, instant Claim 1 fails to recite that the step of lyophilizing a composition comprising exosomes occurs in the presence of a detergent.
Claim Rejections - 35 USC § 103
13. The prior rejections of Claims 1 and 3-4 under 35 U.S.C. 103(a) over Seow et al (U.S. 2013/0053426; of record), Wood et al (U.S. 2014/0348904; of record), Larocca et al (U.S. 2016/010368; of record), and Law et al (U.S. 2017/0252379; of record), respectively, are withdrawn in light of Applicant’s amendments to independent Claim 1, and newly presented Claims 14-17. See new grounds of rejections above.
Double Patenting
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. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); 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); 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) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
14. Claims 1, 3-4, and 14-17 on the ground of nonstatutory double patenting as being unpatentable over claims 24-27 of U.S. Patent No. 10,596,123 in view of Seow et al (U.S. 2013/0053426; of record) and Law et al (U.S. 2017/0252379; of record).
‘123 claims a composition comprising microvesicles according to the method of claim 1, said composition further comprising a carrier. ‘123 claims wherein the microvesicles comprising platelet exosome material and an encapsulant.
‘123 does not claim wherein the exosomes are loaded with a heterologous therapeutic molecule.
However, prior to the effective filing date of the instantly claimed invention, Seow et al disclosed exosomes loaded with genetic material comprising nucleic acids for gene therapy and gene silencing (e.g. [0006]), wherein said exosomes are purified (e.g. [0092], “to purify the exosomes”; [0122], “then purified the exosomes”).
Seow et al successfully demonstrated the ability to introduce a heterologous therapeutic molecule into exosomes, e.g. transfecting the host cell with a nucleic acid expressing said therapeutic molecule, or electroporating said exosome (e.g. [0017-18, 90, 92]).
Similarly, Law et al disclosed compositions comprising placenta-derived adherent cell exosomes ([0003, 35]) comprising one or more nucleic acids comprising a small interfering RNA (siRNA) or an miRNA or one or more gene-modifying components, e.g. gRNA ([0031]-[0032]) loaded into said exosomes (e.g. [0247]), whereby said exosomes are purified (e.g. [0260], “The purified exosomes”; Example 3).
Law et al disclosed the ability to introduce a heterologous therapeutic molecule into exosomes e.g. by electroporation of the exosomes (e.g. [0029]).
‘123 does not recite the Product-by-Process steps of the instant claims.
However, the recitation of a process limitation in Claims 1 and 14-17 is/are not viewed as positively limiting the claimed product absent a showing that the process of making recited in Claims 1 and 14-17 imparts a novel or unexpected property to the claimed product of exosomes comprising a heterologous therapeutic component as it is assumed that equivalent products are obtainable by multiple routes. The burden is placed upon the applicants to establish a patentable distinction between the claimed and referenced products. The method in which the exosomes comprising a heterologous therapeutic component were produced is immaterial to their patentability.
"Even though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 227 USPQ 964, 966 (Fed. Cir. 1985). See also MPEP §2113.
See also discussions above per the 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, and 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, rejections.
The instantly claimed Product-by-Process steps are recited at a high level of generality, and Applicant fails to provide objective evidence as to how the exosomes produced by the instantly recited process steps is/are materially, structurally, and/or functionally different from the prior art exosomes, including the ‘123 exosomes, modified to comprise a heterologous therapeutic component.
It would have been obvious to one of ordinary skill in the art to modify the exosomes of ‘123 to further comprise a heterologous therapeutic molecule with a reasonable expectation of success because those of ordinary skill in the art had long-recognized and successfully reduced to practice the ability to modify exosomes to comprise the artisan’s therapeutic molecule of interest.
It is proper to "take account of the inferences and creative steps that a person of ordinary skill in the art would employ." KSR Int'l Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741,82 USPQ2d 1385, 1396 (2007). See also Id. At 1742, 82 USPQ2d 1397 ("A person of ordinary skill is also a person of ordinary creativity, not an automaton.").
It should be noted that the KSR case forecloses the argument that a specific teaching, suggestion, or motivation is required to support a finding of obviousness. See the recent Board decision Ex parte Smith, —USPQ2d—, slip op. at 20, (Bd. Pat. App. & Interf. June 25, 2007) (citing KSR, 82 USPQ2d at 1396) (available at http: www. uspto.gov/web/offices/dcom/bpai/prec/fd071925 .pdf).
With respect to Claim 3, Seow et al disclosed examples of heterologous nucleic acids such as plasmid DNA and RNAi molecules (paragraphs [0033], [0037]). The nucleic acids are considered to be “native”, in that they are not required to be chemically modified, as per instant specification (pg 4, lines 15-16). Seow et al disclosed, for example, a working example of transfecting or electroporating exosomes with a chemically unmodified plasmid [0112-113].
Law et al disclosed that “e.g., pharmaceutical agent, loaded into the placenta-derived adherent cell exosomes described herein comprises one or more nucleic acids. In specific embodiments, the one or more nucleic acids comprise a siRNA or a miRNA” ([0033]). The nucleic acids are considered to be “native”, in that they are not required to be chemically modified, as per instant specification (pg 4, lines 15-16).
With respect to Claim 4, Seow et al disclosed the heterologous nucleic acids for gene therapy include treatment of hemophilia B, cystic fibrosis or spinal muscular atrophy [0035], and thus the ordinary artisan would have reasonably inferred the gene therapy nucleic acid to encode a therapeutic protein such as Factor IX, CFTR, or SMN-1.
The cited prior art meets the criteria set forth in both Graham and KSR, and the teachings of the cited prior art provide the requisite teachings and motivations with a clear, reasonable expectation of success. Thus, the invention as a whole is prima facie obvious.
15. Claims 1, 3-4, and 14-17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 35-37 of U.S. Patent No. 12,036,325 in view of Seow et al (U.S. 2013/0053426; of record) and Law et al (U.S. 2017/0252379; of record).
‘325 claims a composition comprising a purified exosome product, wherein said exosomes are spherical or spheroidal.
‘325 does not claim wherein the exosomes are loaded with a heterologous therapeutic molecule.
However, prior to the effective filing date of the instantly claimed invention, Seow et al disclosed exosomes loaded with genetic material comprising nucleic acids for gene therapy and gene silencing (e.g. [0006]), wherein said exosomes are purified (e.g. [0092], “to purify the exosomes”; [0122], “then purified the exosomes”).
Seow et al successfully demonstrated the ability to introduce a heterologous therapeutic molecule into exosomes, e.g. transfecting the host cell with a nucleic acid expressing said therapeutic molecule, or electroporating said exosome (e.g. [0017-18, 90, 92]).
Similarly, Law et al disclosed compositions comprising placenta-derived adherent cell exosomes ([0003, 35]) comprising one or more nucleic acids comprising a small interfering RNA (siRNA) or an miRNA or one or more gene-modifying components, e.g. gRNA ([0031]-[0032]) loaded into said exosomes (e.g. [0247]), whereby said exosomes are purified (e.g. [0260], “The purified exosomes”; Example 3).
Law et al disclosed the ability to introduce a heterologous therapeutic molecule into exosomes e.g. by electroporation of the exosomes (e.g. [0029]).
‘325 does not recite the Product-by-Process steps of the instant claims.
However, the recitation of a process limitation in Claims 1 and 14-17 is/are not viewed as positively limiting the claimed product absent a showing that the process of making recited in Claims 1 and 14-17 imparts a novel or unexpected property to the claimed product of exosomes comprising a heterologous therapeutic component as it is assumed that equivalent products are obtainable by multiple routes. The burden is placed upon the applicants to establish a patentable distinction between the claimed and referenced products. The method in which the exosomes comprising a heterologous therapeutic component were produced is immaterial to their patentability.
"Even though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 227 USPQ 964, 966 (Fed. Cir. 1985). See also MPEP §2113.
See also discussions above per the 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, and 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, rejections.
The instantly claimed Product-by-Process steps are recited at a high level of generality, and Applicant fails to provide objective evidence as to how the exosomes produced by the instantly recited process steps is/are materially, structurally, and/or functionally different from the prior art exosomes, including the ‘325 exosomes, modified to comprise a heterologous therapeutic component.
It would have been obvious to one of ordinary skill in the art to modify the exosomes of ‘123 to further comprise a heterologous therapeutic molecule with a reasonable expectation of success because those of ordinary skill in the art had long-recognized and successfully reduced to practice the ability to modify exosomes to comprise the artisan’s therapeutic molecule of interest.
It is proper to "take account of the inferences and creative steps that a person of ordinary skill in the art would employ." KSR Int'l Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741,82 USPQ2d 1385, 1396 (2007). See also Id. At 1742, 82 USPQ2d 1397 ("A person of ordinary skill is also a person of ordinary creativity, not an automaton.").
It should be noted that the KSR case forecloses the argument that a specific teaching, suggestion, or motivation is required to support a finding of obviousness. See the recent Board decision Ex parte Smith, —USPQ2d—, slip op. at 20, (Bd. Pat. App. & Interf. June 25, 2007) (citing KSR, 82 USPQ2d at 1396) (available at http: www. uspto.gov/web/offices/dcom/bpai/prec/fd071925 .pdf).
With respect to Claim 3, Seow et al disclosed examples of heterologous nucleic acids such as plasmid DNA and RNAi molecules (paragraphs [0033], [0037]). The nucleic acids are considered to be “native”, in that they are not required to be chemically modified, as per instant specification (pg 4, lines 15-16). Seow et al disclosed, for example, a working example of transfecting or electroporating exosomes with a chemically unmodified plasmid [0112-113].
Law et al disclosed that “e.g., pharmaceutical agent, loaded into the placenta-derived adherent cell exosomes described herein comprises one or more nucleic acids. In specific embodiments, the one or more nucleic acids comprise a siRNA or a miRNA” ([0033]). The nucleic acids are considered to be “native”, in that they are not required to be chemically modified, as per instant specification (pg 4, lines 15-16).
With respect to Claim 4, Seow et al disclosed the heterologous nucleic acids for gene therapy include treatment of hemophilia B, cystic fibrosis or spinal muscular atrophy [0035], and thus the ordinary artisan would have reasonably inferred the gene therapy nucleic acid to encode a therapeutic protein such as Factor IX, CFTR, or SMN-1.
The cited prior art meets the criteria set forth in both Graham and KSR, and the teachings of the cited prior art provide the requisite teachings and motivations with a clear, reasonable expectation of success. Thus, the invention as a whole is prima facie obvious.
Conclusion
16. Claims 1, 3-4, and 14-17 are rejected.
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 KEVIN K. HILL whose telephone number is (571)272-8036. The examiner can normally be reached 12pm-8pm EST.
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KEVIN K. HILL
Examiner
Art Unit 1638
/KEVIN K HILL/Primary Examiner, Art Unit 1638