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 .
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
DETAILED ACTION
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 12/9/25 has been entered.
Applicant’s election of Group II, ARPE-19 cells, the elected chemical structure, the compound is part of the enclosing component, alginate, FVII-BDD (Seq 1), and SEQ 15 in the reply filed 9/12/22 remains in effect.
Claims 46-48, 50-51, 53, 55-59, 62-64 are pending. Claims 51 and 59 are withdrawn as being drawn to non-elected subject matter. Election was made without traverse on 9/12/22.
Claims 46-48, 50, 53, 55-58, and 62-64 are under examination.
Priority
Applicant “strongly contests” the priority determination but does not state any specific reason in support of this protest. Applicant’s mere assertion does not amount to objective evidence nor a specific criticism of the determination. As such, Applicant’s response to the priority determination is insufficient on its face because Applicant does not point to any alleged deficiency.
Note that Applicant also did not provide any support nor articulate any alleged deficiency in the response filed 5/21/25 (see final action 9/17/25). For the Office’s analysis of Applicant’s most recent response which addressed the merits of the determination, see Office action mailed 2/21/25.
Claim Objections
Claim 50 is objected to because of the following informalities: there is no terminal conjunction (e.g., “or” or “and”) prior to the last element in line 7. Appropriate correction is required.
Current Rejections
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 46, 47, 53, 55, 56, 62, 63, and 64 is/are rejected under 35 U.S.C. 103 as being unpatentable over Vegas in view of Fjord-Larsen (Fjord) and Kitchen.
Regarding claim 46, claim 46 recites an implantable element comprising an engineered cell that produces or releases a therapeutic agent wherein the engineered active cell comprises a human retinal pigment epithelial cell (RPE) or a cell derived therefrom, wherein the therapeutic is a polypeptide which is FVII-BDD, wherein the implantable element comprises an enclosing component surrounding the engineered active cell or plurality of engineered active cells, wherein the enclosing component comprises an alginate, wherein the alginate is modified with a compound selected from a compound of Formulas (II-a), (II-d), and (IV-a) which is described in the instant application.
Vegas teaches an element comprising encapsulated cells which secrete a therapeutic factor (paragraph [0152]). Vegas also teaches that this element has an enclosing component comprised of alginate and is implantable (claims 1, 16, 18). Vegas further teaches that the enclosing alginate is modified with triazole-thiomorpholine dioxide, a compound equivalent to compound no. 101 of the instant application and is thus within the scope of Formulas (II-a), (II-d), and (IV-a) (Fig. 13).
Fjord teaches that genetically engineered ARPE-19 cells have been successfully encapsulated in bio-delivery devices implanted into the forebrain of model animals to deliver a therapeutic polypeptide, NGF, in vivo (Materials and Methods – Cell culture and transfection). Furthermore, the implantable element of Vegas may contain cells which produce insulin, a therapeutic polypeptide (claims 1, 16, 18, 21). The ARPE-19 cells of Fjord and the instant application fall within the scope of "cells" as
described by Vegas (claim 18).
Kitchen teaches that FVIII is deficient in hemophilia A and that recombinant (produced in cells) FVIII is used in the treatment of hemophilia A (page 331). Kitchen further teaches that B-domain deleted
recombinant FVIII is an effective FVIII replacement (page 332). Kitchen also teaches efforts to increase the longevity of FVIII activity are crucial for hemophilia care to reduce prophylactic injections of FVIII and/or to increase the trough level prior to injections (abstract).
It would have been obvious at the time of filing to combine the ARPE-19 cells of Fjord with the implantable element of Vegas because ARPE-19 cells were known to be combinable with bio-delivery devices such as the element of Vegas. It would have been obvious to combine the ARPE-19 cells of Fjord with the FVIII-BDD of Kitchen with the element Vegas in order to create an implantable element which secretes FVIII-BDD because implantable bio-delivery devices were known at the time of filing to be combined with ARPE-19 cells which secrete therapeutic polypeptides and FVIII-BDD was a known treatment for hemophilia A. The substitution of pancreatic islet cells with ARPE-19 cells and insulin for FVIII-BDD had a reasonable expectation of success based on the state of the art at the time of filing.
Regarding claim 47, claim 47 further specifies the implantable element of 46 wherein the engineered active cell is a human engineered ARPE-19 cell and the therapeutic agent is encoded by an exogenous nucleic acid in the ARPE-19 cell. The condition of the engineered active cell being an engineered ARPE-19 cell is taught by Fjord as above. Fjord also teaches genetically engineered ARPE-19 cells which express polypeptides encoded by exogenous nucleic acids (Materials and Methods - Cell
culture and transfection). Fjord teaches that genetically engineered ARPE-19 cells can be used as a source for therapeutic polypeptides, such as NGF (Materials and Methods - Western blotting). Vegas teaches that the implantable element with encapsulated human cells achieves long-term therapeutic production over 170 days (paragraph [0303]). This long-term production of therapeutics provides motivation to combine the implantable element with ARPE-19 cells, and FVIII-BDD. Combining the implantable element of Vegas, the ARPE-19 cells of Fjord, and the FVIII-BDD polypeptide of Kitchen would person of ordinary skill in the art at the time of filing because Vegas provides the basic structure of the element, the cells, and a therapeutic polypeptide.
Regarding claim 53, claim 53 further specifies the implantable element of 46, wherein the compound of Formulas (II-a), (II-d), or (IV-a) is compound no. 101. As described above, Vegas teaches the implantable element of 46 modified with compound 101.
Regarding claim 55, claim 55 further specifies the implantable element of claim 46, which comprises at least about 10,000 of the engineered ARPE-19 cell. Fjord teaches 75,000 engineered ARPE-19 cells which are encapsulated in an implantable biodelivery device (Materials and Methods -
Encapsulation of NGC-0295 in experimental devices) and would have made instant claim 55 obvious.
Regarding claim 56, claim 56 further specifies a pharmaceutical composition comprising a plurality of the implantable element of claim 46 in a pharmaceutically acceptable carrier. Vegas specifies that the object of the invention described is to provide polymers for coating devices where the polymers
have increased biocompatibility following implantation of the device (paragraph [0012]). The implantable device of Vegas is coated in a modified alginate which enhances pharmaceutical acceptability and thus meets the limitations of claim 56.
Claim 62 further specifies the implantable element of claim 55, wherein the ARPE-19
cells are disposed on a microcarrier. The instant disclosure specifies that a bead or matrix which can comprise cells of interest is an example of a microcarrier. Vegas teaches that cells of interest can be
suspended in a hydrogel matrix (paragraph [0407]) and thus meets the limitations of instant claim 62.
Claim 63 further specifies the implantable element of claim 46, wherein the implantable
element has a mean diameter that is between 1 mm and 2 mm. Vegas teaches implantable elements which have a mean diameter from about 150 µm to about 5 cm, preferably greater than 1 mm and specifies size ranges of said elements which encompass the 1 mm to 2 mm specified in instant claim 63
(paragraph [0298]).
Claim 64 further specifies the implantable element of 46, wherein the compound of
Formulas (II-a), (II-d), or (IV-a) is compound no. 101. As described above, Vegas, Fjord-Larsen, and Kitchen teach the implantable element of claim 47 and Vegas specifically teaches the modification of the element with compound no. 101.
Therefore, claims 46, 47, 53, 55, 56, 62, 63, and 64 would have been obvious.
Claim(s) 48 is/are rejected under 35 U.S.C. 103 as being unpatentable over Vegas in view of Fjord-Larsen (Fjord) and Kitchen, as applied to claims 46, 47, 53, 55, 56, 62, 63, and 64 above, and further in view of Widdowson (AU2018248651).
Regarding claim 48, the claim further specifies the implantable element of claim 47, wherein the exogenous nucleic acid is a transcription unit which comprises a promotor sequence operably linked to a
coding sequence for the polypeptide, wherein the promoter sequence consists essentially of, or
consists of SEQ ID NO:23 or has at least 95% or greater sequence identity with SEQ ID NO:23. Note that Applicant defines “consists essentially of” on page 10 of the specification, defining the phrase as including “similar or different” elements that do not materially change the basic or novel properties. The specification at this point describes explicitly non-limiting examples. As per MPEP §2111, “absent a clear indication in the specification or claims of what the basic and novel characteristics actually are, ‘consisting essentially of’ will be construed as equivalent to ‘comprising.’” The examples include reference to the “relevant” biological activities; this could be referring to any number of biological activities and the specification does not indicate which activities are relevant. In another example, the characteristics of the promoter are the amount of transcription determined by quantifying RNA or protein levels. The use of “e.g.” indicates there is some other, unnamed relevant biological activity as well as leaving doubt as to whether quantification in some form is required or if the activity can be changed so long as it is not measured. As the specification gives examples of these characteristics which are explicitly non-limiting, this in not considered a “clear” indication of what these characteristics are for evaluation of the phrase. As such, the phrase is being interpreted as “comprising”.
Claims 46 and 47 are obvious over Vegas, Fjord-Larsen, and Kitchen as above and incorporated herein. Widdowson teaches a promoter comprised of a sequence identical to instant SEQ ID NO:23 operably linked to a coding sequence (SEQ ID NO: 2, claims 1,3). It would have been obvious to combined the promoter sequence of Widdowson with the implantable element of claim 47 because Widdowson discloses the promoter sequence to initiate transcription of the RNA necessary to produce polypeptides (“The promoter of the construct may be used to ensure that the agonist and the receptor are…expressed”; “promoter operably linked to a first coding sequence, which encodes the tyrosine kinase receptor B”) and a person of ordinary skill in the art would have recognized at the time of filing that this promoter could be used to promote expression of another protein/peptide, such as the one discussed above and now claimed.
Therefore, claim 48 would have been obvious.
Claim(s) 50 is/are rejected under 35 U.S.C. 103 as being unpatentable over Vegas in view of Fjord-Larsen (Fjord) and Kitchen, as applied to claims 46, 47, 53, 55, 56, 62, 63, and 64 above, and further in view of Donovan (CA3189640).
Regarding claim 50, the claim specifies the implantable element of 47, wherein the therapeutic agent is a FVIII-BDD of polypeptide which comprises, consists essentially of, or consists of SEQ ID NO: 1
and the exogenous nucleic acid comprises a coding sequence which comprises, consists
essentially of, or consists of SEQ ID NO: 15; note that “consists essentially of” has the same meaning as “comprising” as set forth above and incorporated herein.
Claims 46 and 47 are obvious over Vegas, Fjord, and Kitchen as above and incorporated herein. Donovan teaches a sequence of FVIII-BDD which corresponds to SEQ ID NO: 1 (SEQ ID NO: 12) and a nucleic acid sequence of SEQ ID NO: 15 (SEQ ID NO: 15). It would have been obvious to a person of ordinary skill in the art at the time of filing to utilize the nucleic acid and amino acid sequences of FVIII-BDD taught by Donovan because one would have found the incorporation of FVIII-BDD obvious as described above (e.g., as disclosed by Kitchen) and Donovan teaches functional sequences of those proteins.
Therefore, claim 50 would have been obvious.
Claim(s) 58 is/are rejected under 35 U.S.C. 103 as being unpatentable over Vegas in view of Fjord-Larsen (Fjord), Kitchen and Widdowson, as applied to claims 46-48, 53, 55, 56, 62, 63, and 64 above, and further in view of Donovan (CA3189640).
Regarding instant claim 58, this claim depends from claim 48 and includes the limitations of claim 50. Claims 46 and 47 would have been obvious over Vegas, Fjord, and Kitchen as above and incorporated herein. Claim 48 would have been obvious as described above and incorporated herein. Claim 50 would have been obvious over Donovan as described above and incorporated herein. Widdowson and Donovan teach separate elements of the composition and so would have been obvious to incorporate for the same reasons as above.
Claim(s) 57 is/are rejected under 35 U.S.C. 103 as being unpatentable over Vegas in view of Fjord-Larsen (Fjord) and Kitchen, as applied to claims 46, 47, 53, 55, 56, 62, 63, and 64 above, and further in view of Little (WO2018213886).
Regarding claim 57, the claim specifies the implantable element of claim 48, wherein the transcription unit further comprises a polyA sequence that consists essentially of, or consists of, SEQ ID NO: 24 or a nucleotide sequence that is at least 95% or more identical to SEQ ID NO: 24. Claim 48 would have been obvious as described above and incorporated herein. Little teaches a polyA sequence that is identical to instant SEQ ID NO: 24 (SEQ ID NO: 20). It would have been obvious to a person of ordinary skill in the art at the time of filing to combine the polyA sequence of Little with the implantable element of claim 48 because Little teaches that polyadenylation sequences are regulator sequences and these sequences are known to increase translational efficiency of mRNA.
Therefore, claim 57 would have been obvious.
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.
Claims 46-48, 50, 53, 55-58, and 62-64 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-27 of U.S. Patent No. 12161760 (reference patent) in view of Kitchen and Donovan and Little (WO2018213886). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Regarding claim 46, the reference claims a first compartment comprising a cell or plurality of cells (claims 1, 6), where the cell is an RPE cell (claim 8) and the cell expresses a therapeutic agent (claim 10). The therapeutic agent is Factor VIII (claim 11). The cell (first compartment) is surrounded (enclosed) by a second compartment (claim 1, 6), which meets the limitations of an “enclosing component”. The second compartment—the enclosing component—comprises an alginate polymer (claim 1), which is “an alginate” and is modified in the same way (claim 1); compare both instant and reference compound 101 as well as reference claim 18 compared to instant claim 53. There is nothing in reference claim 1 to suggest the particle is not implantable and so meets the limitations of “an implantable element”. Thus, instant claim 46 differs from reference claim 1 only in that the reference claim does not specify the FVIII is an FVIII-BDD.
Nevertheless, it would have been obvious to incorporate FVIII-BDD into the reference particle/element. First, those portions of the specification which provide support for the patent claims may also be examined and considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the patent. In re Vogel, 422 F.2d 438, 441-42, 164 USPQ 619, 622 (CCPA 1970). In this case, in support of the explicitly claimed “variant” of Factor VIII in claim 11, the reference document discloses the preferred FVIII-BDD (figure 2A; figure 17A+; C4-6). Further, Kitchen teaches that B-domain deleted recombinant FVIII is an effective FVIII replacement (page 332). It would have been obvious to substitute FVIII with FVIII-BDD because the art explicitly teaches this is an effective substitution.
The claims also differ in that the instant claim specifies the RPE cell is human. However, the reference specification may be used as a dictionary to learn the meaning of a term in a patent claim; see also Toro Co. v. White Consol. Indus., Inc., 199 F.3d 1295, 1299, 53 USPQ2d 1065, 1067 (Fed. Cir. 1999), Renishaw PLC v. Marposs Societa' per Azioni, 158 F.3d 1243, 1250, 48 USPQ2d 1117, 1122 (Fed. Cir. 1998), and MPEP 2111.01. The reference specification explicitly defines “RPE cell” to be “from a human or other mammal” (C18), making a human cell an obvious variation.
Regarding claim 47, reference claim 22 claims the cell is from ARPE-19 and comprises an exogenous nucleotide.
Regarding claim 48, reference claim 22 claims SEQ ID NO: 23
Regarding claim 50, reference claim 22 claims SEQ ID NO: 17 and exemplifies SEQ ID NO: 1 for the FVIII-BDD, which would have been obvious as above. See also Donovan’s disclosure of SEQ ID NO: 1 which would have been obvious as above.
Regarding claim 53, this modification would have been obvious as above, e.g., reference claim 18.
Regarding claim 55, ARPE-19 cells would have been obvious as above. Reference claim 21 claims a minimum of 50 million cells/mL as well as other concentrations. Where the number of cells is recognized as a result-effective variable, such as it is in reference claim 21, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP §2144.05(II).
Regarding claim 56, the first compartment comprises an alginate polymer separate from the alginate encapsulating the cell (claim 1), i.e., a pharmaceutically acceptable carrier.
Regarding claim 57, Little would have made obvious the poly A sequence as described in the §103 rejection above and incorporated herein.
Regarding claim 58, these limitations would have been obvious as above.
Regarding claim 62, the first compartment comprises an alginate polymer separate from the alginate encapsulating the cell (claim 1), e.g., a matrix or microcarrier. The cells are also disclosed as being “attached to a microcarrier”, which meets the definition of “disposed on”.
Regarding claim 63, the reference claims the particle (i.e., the implantable element) has a diameter (largest linear dimension) of 1.5-2mm (claim 4).
Regarding claim 64, this compound would have been obvious as above.
Therefore, claims 46-48, 50, 53, 55-58, and 62-64 would have been obvious.
Claims 46-48, 50, 53, 55-58, and 62-64 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, 8-10, 12, 14, 28, 31-32, 41, and 42 of copending Application No. 17280802 (reference application) in view of Donovan and Little and Vegas. Although the claims at issue are not identical, they are not patentably distinct from each other because:
Regarding claim 46, the reference claims a hydrogel comprising a “cell-containing compartment” which comprises a plurality of engineered RPE cells where the RPE produces or releases a therapeutic agent (claim 1). The therapeutic agent is Factor VIII (claim 9). The cell is surrounded (enclosed) by a barrier compartment (claim 1), which meets the limitations of an “enclosing component”. The second compartment—the barrier component—comprises a modified alginate (claim 1), which is “an alginate” and is modified in the same way (claims 1; 8); compare both instant and reference compound 101 as well as reference claim 8 compared to instant claim 53. There is nothing in reference claim 1 to suggest the hydrogel is not implantable and so meets the limitations of “an implantable element”. Reference claim 31 claims the FVIII is an FVIII-BDD.
The claims differ in that the instant claim specifies the RPE cell is human. However, the reference specification may be used as a dictionary to learn the meaning of a term in a patent claim; see also Toro Co. v. White Consol. Indus., Inc., 199 F.3d 1295, 1299, 53 USPQ2d 1065, 1067 (Fed. Cir. 1999), Renishaw PLC v. Marposs Societa' per Azioni, 158 F.3d 1243, 1250, 48 USPQ2d 1117, 1122 (Fed. Cir. 1998), and MPEP 2111.01. The reference specification explicitly defines “RPE cell” to be “from a human or other mammal” (paragraph 129), making a human cell an obvious variation.
Regarding claim 47, reference claim 10 claims the cell is from ARPE-19 and claim 1 states the cells comprise an exogenous nucleotide.
Regarding claim 48, reference claim 14 claims a promoter sequence. In looking to the specification for support (Vogel), paragraph 313 discloses only two: SEQ ID NO: 23 and 26. This would have made SEQ ID NO: 23 an obvious variation.
Regarding claim 50, reference claim 32 claims SEQ ID NO: 15 and, in support of the claim to FVIII-BDD, discloses SEQ ID NO: 1 (paragraph 45). See also Donovan’s disclosure of SEQ ID NO: 1 which would have been obvious as above.
Regarding claim 53, this modification would have been obvious as above, e.g., reference claim 8.
Regarding claim 55, ARPE-19 cells would have been obvious as above. Reference claim 32 claims a minimum of 35 million cells/mL as well as other concentrations. Where the number of cells is recognized as a result-effective variable, such as it is in reference claim 32, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP §2144.05(II).
Regarding claim 56, the first compartment comprises an alginate polymer separate from the alginate encapsulating the cell (claim 1), i.e., a pharmaceutically acceptable carrier.
Regarding claim 57, reference claim 14 claims the polyA sequence. Little would have made obvious the specific poly A sequence as described in the §103 rejection above and incorporated herein.
Regarding claim 58, these limitations would have been obvious as above.
Regarding claim 62, the first compartment comprises an alginate polymer separate from the alginate encapsulating the cell (claim 1), e.g., a matrix or microcarrier. The cells are also claimed as in the same compartment as a cell-binding peptide as well as in a hydrogel, meeting the limitations of “disposed on”.
Regarding claim 63, the reference does not claim a size of the hydrogel. Vegas also teaches encapsulation in a hydrogel matrix and specifies size ranges of said elements which encompass the 1 mm to 2 mm.
Regarding claim 64, this compound would have been obvious as above.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Applicant's arguments filed 12/9/25 have been fully considered but they are not persuasive.
Applicant argues that “specifically, nothing in Vegas provides that the secreted factor is a FVIII-BDD”. This is not persuasive because Vegas is not relied on for this teaching.
Applicant argues there are “tens of thousands of proteins encoded in the human genome, any of which could have therapeutic potential”. While true, this does not address the teachings of Kitchen, which is specifically that FVIII-BDD is an effective therapeutic.
Applicant argues there is no motivation to include FVIII-BDD when reading Vegas. First, such motivation need not be found in Vegas alone. One cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Second, there is no requirement for a strict motivation. In this case, KSR establishes as one potential avenue of obviousness the “simple substitution”, e.g., substituting one known therapeutic protein for another. The claims are not a method of treatment and so the obviousness analysis, including for substitution, is whether or not that substitution was within the ordinary skill and knowledge at the time of filing; note that KSR uses the word “could”—not “would”—when setting forth the steps of the analysis. No specific effect of the claimed “element” needs to result and MPEP 2141(II)(C) states "a person of ordinary skill in the art is also a person of ordinary creativity, not an automaton." KSR, 550 U.S. at 421, 82 USPQ2d at 1397. "[I]n many cases a person of ordinary skill will be able to fit the teachings of multiple patents together like pieces of a puzzle." Id. at 420, 82 USPQ2d at 1397. Office personnel may also take into account "the inferences and creative steps that a person of ordinary skill in the art would employ." Id. at 418, 82 USPQ2d at 1396. A person of ordinary skill in the art could have made the above combinations with a reasonable expectation that the protein would still be expressed, as RPE has been used to express therapeutic proteins and FVIII-BDD has been expressed by cells.
Applicant argues there is no reasonable expectation of success to produce a peptide even if the cell was used to produce other peptides. Applicant provides no evidence of this assertion. Applicant is reminded that “arguments of counsel cannot take the place of factually supported objective evidence" (MPEP§2415).
Applicant argues that Fjord’s device is “irrelevant”. This does not point to any specific deficiencies in the articulated reasons Fjord is considered relevant in the rejection of record. Applicant reiterates Fjord does not teach FVIII-BDD and other elements which Fjord was not relied on for teaching. As above, an argument that an individual reference does not teach the whole of the claim is not a persuasive argument when the rejection is based on multiple references.
Similarly, Applicant argues Kitchen does not teach RPE cells, implantable elements, encapsulated cells, etc., none of which were teachings Kitchen was relied on for. Applicant argues impermissible hindsight but does not point to any aspect of the combination that could only be gleaned from Applicant’s specification. It must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
Applicant argues the combinations would never be combined because there is no common thread. This argument is not persuasive because it does not address the rationale set forth in the rejection. Vegas teaches encapsulated cells where the cells express a therapeutic. Fjord teaches aspects of those cells which can be used to express therapeutics and Kitchen teaches an alternate therapeutic to be expressed. The end result would be the predictable outcome of modified alginate encapsulated cells expressing a therapeutic, which would have been obvious given the teachings as described. That there are differences, e.g., that Fjord uses membrane tubes, is not persuasive because the test of obviousness is not whether one reference may be bodily incorporated into another (MPEP §2145). Applicant’s mere assertion that there would be significant experimentation or not be possible without any objective evidence in support of those assertions is not deemed persuasive.
Applicant’s arguments against the inclusion of Widdowson are similar. Applicant argues Widdowson does not teach every element, which is not a proper argument against a rejection based on multiple references. Applicant argues there is no “guarantee” of success; absolute predictability is not the bar of obviousness but rather reasonable expectation of success and Applicant has provided no objective evidence to undermine the assertions of the rejection. Applicant argues impermissible hindsight without pointing to a specific fact gleaned only from Applicant’s disclosure.
Applicant’s arguments against Little are similar and are not persuasive for the same reasons. It is noted that Applicant agrees the addition of polyA is “commonly added to recombinant expression constructs” (12/9/25 p.10).
Regarding the double patenting rejections, Applicant argues the two reference documents do not disclose “particularly RPE cells”. This is not persuasive because both have explicit claims to RPE cells. A mere allegation of “due to many distinctions” or the broad assertion that the references do not disclose “all the features” is an incomplete response as it does not attempt to point to any specific deficiency in the rejection.
It is noted that Applicant has requested a telephone call if the application is not in condition for allowance. An interview prior to reading the instant office action would be premature and not deemed likely to advance prosecution. Once Applicant has had a chance to review the Office Action, Applicant may make a formal request for an interview at that time.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ADAM M WEIDNER whose telephone number is (571)272-3045. The examiner can normally be reached M-T 9-18; W-R 9-15.
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/Adam Weidner/ Primary Examiner, Art Unit 1675