DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
The instant application is a divisional under 35 USC § 121 of US Application No. 16/966406, filed 30 July 2020 (now US Patent 12,038,432 B2, issued 20 May 2025), which is a national stage entry under 35 USC 371 of PCT/US2019/016236, filed 01 February 2019. Acknowledgment is made of Applicant’s claim for benefit under 35 USC 119(e) to US Provisional Application No. 62625628, filed 02 February 2018.
Status of the Claims
Instant claims 1-19, of record 03 June 2024, are pending. Therefore, prosecution on the merits commences for claims 1-19.
Claim Objections
Claim 19 is objected to because of the following informalities:
Regarding claim 19: The instant claim is objected to for reciting “… responsive to contacting the compound of interest to the construct and/or the live tumor cell organoid, determining the growth of the live tumor cells, a decrease in growth of the live tumor cells indicating anti-tumor activity of the compound of interest, and/or determining an immunological response of the immune cell organoid and/or the live tumor cell organoid” instead of “… responsive to contacting the compound of interest to the construct and/or the live tumor cell organoid, determining the growth of the live tumor cells, wherein a decrease in growth of the live tumor cells indicates an anti-tumor activity of the compound of interest, and/or determining an immunological response of the immune cell organoid and/or the live tumor cell organoid”, or the like. The amendment is required to more clearly indicate that the decrease in live tumor cell growth is a possible alternative in the determination of the growth of the live tumor cells.
Appropriate correction is required.
Claim Interpretation
The instant Specification defines the term “take rate” as the percentage of the time a viable organoid or plurality of organoids (e.g., an organoid set) is achieved and/or provided by a method of the present invention. For instance, for a 90% take rate, 9 out of 10 cell samples (e.g., tumor cell samples) yield a viable organoid or plurality of organoids when prepared according to a method of the present invention. See Paragraph [0102] of the published Specification.
With that, instant claim 11 is directed to a product which utilizes product-by-process language. The limitations of the process of production are considered only in so far as the process of production imparts distinct structural or chemical characteristics or properties to the claimed product. Therefore, if the product, as claimed, is the same or obvious over a product of the prior art (i.e. is not structurally or chemically distinct), the claim is considered unpatentable over the prior art, even though the prior art product is made by a different process. See MPEP § 2113.
Claim 11 defines the method in which the tumor cells, the at least one type of live immune cell, and benign cells are prepared, wherein the method has a take rate of at least 50%. In the instant case, there is no evidence that the preparation method imparts any particular structure or significance to the tumor cells, the at least one type of live immune cell, or benign cells other than requiring at least 50% of the produced constructs to be viable.
Therefore, claim 11 will be interpreted as if constructs comprising tumor cells, at least one type of live immune cell, and/or benign cells prepared by any method fulfills the limitation detailed in the instant claim, so long as at least 50% of the produced constructs are viable.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 7 and 11 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.
Regarding claim 7: The instant claim recites the limitation “wherein the live tumor cells and the at least one type of live immune cell are present in the construct in a ratio of about 1:1 to about 100:1 (tumor cells: immune cells)”. The scope of the claim is indefinite, as it is unclear if the parenthetical language is required by the claim, or is instead optional. Therefore, since the recitation of the parenthetical language is being treated as exemplary language, the metes and bounds of the claim cannot be determined.
Appropriate correction is required.
Regarding claim 11: The instant claim recites the limitation "the benign cells" in Line 2. There is insufficient antecedent basis for this limitation in the claim, as there is no prior recitation of “benign cells” within the instant claim or parent claim 1. Therefore, the metes and bounds of the claim cannot be determined, thus rendering the scope of the claim indefinite. See MPEP § 2173.05(e).
Appropriate correction is required.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-16 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a nature-based product without significantly more.
Independent claim 1 is directed to an in vitro cell construct comprising live tumor cells and at least one type of live immune cell. Likewise, independent claim 15 is directed to an in vitro cell construct comprising a plurality of live immune cells.
The test for 101 eligibility of judicial exceptions can be found at MPEP § 2106:
“First, the claimed invention must be to one of the four statutory categories. 35 U.S.C. 101 defines the four categories of invention that Congress deemed to be the appropriate subject matter of a patent: processes, machines, manufactures and compositions of matter.”
“Second, the claimed invention also must qualify as patent-eligible subject matter, i.e., the claim must not be directed to a judicial exception unless the claim as a whole includes additional limitations amounting to significantly more than the exception. The judicial exceptions (also called "judicially recognized exceptions" or simply "exceptions") are subject matter that the courts have found to be outside of, or exceptions to, the four statutory categories of invention, and are limited to abstract ideas, laws of nature and natural phenomena (including products of nature). Alice Corp. Pty. Ltd. v. CLS Bank Int'l, 573 U.S. 208, 216, 110 USPQ2d 1976, 1980 (2014) (citing Ass'n for Molecular Pathology v. Myriad Genetics, Inc., 569 U.S. 576, 589, 106 USPQ2d 1972, 1979 (2013).”
“The Supreme Court in Mayo laid out a framework for determining whether an applicant is seeking to patent a judicial exception itself, or a patent-eligible application of the judicial exception. See Alice Corp., 573 U.S. at 217-18, 110 USPQ2d at 1981 (citing Mayo, 566 U.S. 66, 101 USPQ2d 1961). This framework, which is referred to as the Mayo test or the Alice/Mayo test, is discussed in further detail in subsection III, below. The first part of the Mayo test is to determine whether the claims are directed to an abstract idea, a law of nature or a natural phenomenon (i.e., a judicial exception). Id. If the claims are directed to a judicial exception, the second part of the Mayo test is to determine whether the claim recites additional elements that amount to significantly more than the judicial exception. Id. citing Mayo, 566 U.S. at 72-73, 101 USPQ2d at 1966). The Supreme Court has described the second part of the test as the "search for an 'inventive concept'". Alice Corp., 573 U.S. at 217-18, 110 USPQ2d at 1981 (citing Mayo, 566 U.S. at 72-73, 101 USPQ2d at 1966).”
Examiners should determine whether a claim satisfies the criteria for subject matter eligibility by evaluating the following steps outlined in a flow chart at MPEP 2106(III) and 2106.04(II)(A):
Step 1: is the Claim to a process, machine, manufacture or composition of matter? If Yes, proceed to Step 2A;
Step 2A, prong one: Is the Claim directed to a law of nature, a natural phenomenon (product of nature), or an abstract idea? If Yes, proceed to Step 2A, prong two;
Step 2A, prong two: Does the claim recite additional elements that integrate the judicial exception into a practical application? If No, proceed to Step 2B;
Step 2B: Does the claim recite additional elements that amount to significantly more (an inventive concept) than the judicial exception? If No, the claim is not eligible subject matter under 35 USC 101.
With regard to Step 1: YES, the each of claims 1 and 15 are directed to composition of matters, or products.
With regard to Step 2A, prong one: YES, the claims are directed to cell constructs that comprise live tumor cells and/or at least one type of live immune cell, which are nature-based products. More specifically, the claimed cell construct comprising live tumor cells and at least one type of live immune cell, and the claimed cell construct comprising a plurality of live immune cells are compared to the closest naturally occurring counterpart, which are cell constructs comprising live tumor cells and/or live immune cells, per se. Thus, there is no marked different between the claims and products of nature – which include tumors. See, for example, Pages 1-2, 6-8 and Figures 1, 3 of Racle et al (eLife, 2017).
With regard to Step 2A, prong two: No, the claims do not include any additional elements that integrate the judicial exceptions into a practical application. Integration into a practical application requires additional elements in the claim to apply, rely on, or use the judicial exception in a manner that imposes a meaningful limit on the judicial exception, such that the claim is more than a drafting effort designed to monopolize the exception.
The claims do not modify or transform the naturally occurring tumor cells and/or immune cells, nor apply the cells for a particular treatment or medical condition, nor impose a meaningful limit on the cells recited therein.
With regard to Step 2B: No, the claims do not provide any additional elements that amount to significantly more (an inventive concept) than the judicial exception.
Taken together, the claims encompass natural products. The judicial exceptions are not integrated into practical applications as iterated above. The claims do not include additional elements
that are sufficient to amount to significantly more than the judicial exceptions as iterated above.
Claims 2-14 are included in the rejection because they fully incorporate the limitations of rejected claim 1 and fail to provide any additional elements that are sufficient to amount to significantly more than the judicial exception or integrate the judicial exception into a practical application. It is of note that detectable compounds (claim 9) and hydrogels (claim 13) can be elements that are naturally comprised within a tumor, and the percentage/ratio of viable cells (claims 7, 11-12) does not alter the structure of the cells, per se.
Claim 16 is also included in the rejection because it fully incorporates the limitations of rejected claim 15 and fails to provide any additional elements that are sufficient to amount to significantly more than the judicial exception or integrate the judicial exception into a practical application.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 15-16 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Purwada et al (Nature Protocols, 2016, of record on IDS filed 03 June 2024) as evidenced by Janeway et al (Immunobiology: The Immune System in Health and Disease, 2001, of record on IDS filed 03 June 2024).
Purwada et al disclose the in vitro generation of an immune cell organoid comprised of purified B cells from 6-8 week old C5BL6 mice (Abstract; Pages 171, 174-176).
Accordingly, Purwada et al anticipates the claim as follows:
Regarding claim 15: Purwada et al disclose the in vitro generation of an immune cell organoid comprised of purified B cells. As an organoid is a cell construct, this therefore reads on the in vitro cell construct of the instant claim.
Regarding claim 16: As aforementioned in the discussion of claim 15, Purwada et al disclose that the immune cell organoid is comprised of purified B cells. As these B cells are inherently derived from bone marrow, this therefore reads on the construct of the instant claim. See Janeway et al: Page 3, 1-2. Lymphocytes mature in the bone marrow or the thymus; Page 6, Summary.
Claims 1-6, 8-11, and 13-19 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Neal et al (US 2018/0119107 A1, of record on IDS filed 03 June 2024) as evidenced by Janeway et al (Immunobiology: The Immune System in Health and Disease, 2001, of record on IDS filed 03 June 2024), National Cancer Institute (NCI Dictionary of Cancer Terms, 2018), and Caliari et al (Nat Methods, 2016, of record on IDS filed 03 June 2024). Neal et al has an effective filing date of 28 October 2016.
Neal et al disclose in vitro culture systems of human solid tumors as three-dimensional patient derived organoids (PDO) that recapitulate the cellular architecture and ultrastructure of the tumor sample from which they were derived, and include immune cells, parenchymal and stromal elements (Paragraphs [0010], [0020], [0028], [0090]-[0095]).
As such, Neal et al disclose that the PDO culture is initiated with a solid tumor sample obtained via needle biopsy, wherein there are sufficient stromal and immune cell components to initiate a complex culture comprising these elements, and is subsequently embedded within a gel substrate (Paragraphs [0011]-[0012], [0030]-[0031], [0068]). Neal et al further disclose that the immune cells include lymphocytes, such as B cells and T cells; natural killer cells; myeloid cells, such as monocytes, macrophages, eosinophils, mast cells, basophils, and granulocytes, and that the tumor cells include benign and malignant cells (Paragraphs [0010], [0013], [0017], [0063], [0029]).
Neal et al further disclose that the PDO is cultured within growth medium for up to 28 days (Paragraphs [0017], [0073]-[0075], [0094]).
Neal et al further disclose a plurality of PDOs in culture are contacted with a candidate agent of interest for a period of time sufficient to allow an effect on the immune cells, and the effect on the tumor and/or immune cells associated with the tumor to be assessed (Paragraphs [0011]-[0012], [0036], [0078]-[0089]). Neal et al note that in some embodiments the candidate agent is screened for activity that is anti-tumorigenic or anti-tumoral (Paragraph [0088]).
Consequently, Neal et al anticipate the claims as follows:
Regarding claims 1-2, 4, and 15: Neal et al disclose three-dimensional human patient derived organoids (PDO) that comprise a plurality of immune cells and tumor cells obtained via a single needle biopsy of the patient’s tumor (claims 2, 4). This therefore reads on the constructs of instant claims 1 and 15.
Regarding claims 3 and 16: Following the discussion of claims 1 and 15, Neal et al further disclose that the plurality of immune cells comprised within the PDO include lymphocytes, such as B cells. As these lymphocytes are inherently derived from bone marrow (claims 3, 16), this therefore reads on the constructs of the instant claims. See Janeway et al: Page 3, 1-2. Lymphocytes mature in the bone marrow or the thymus; Page 6, Summary.
Regarding claim 5: Following the discussion of claim 1, Neal et al further disclose that the PDO comprises a plurality of immune cells including B cells, T cells, and myeloid cells. This therefore reads on the construct of the instant claim.
Regarding claim 6: Following the discussion of claim 1, Neal et al further disclose that the plurality of immune cells comprised within the PDO include lymphocytes, such as B cells. As B cells are inherently a type of white blood cell, this therefore reads on the construct of the instant claim. See the National Cancer Institute reference: Page 1.
Regarding claim 8: Following the discussion of claim 1, Neal et al further disclose that the PDO can comprise benign cells. This therefore reads on the construct of the instant claim.
Regarding claim 9: Following the discussion of claim 1, Neal et al further disclose that the immune cells comprised within the PDO are positive for PD-1 (Paragraph [0094]; Figure 3A). As PD-1 is a detectable compound, this therefore reads on the construct of the instant claim.
Regarding claim 10: Following the discussion of claim 1, Neal et al further disclose that the PDO is in culture for up to 28 days. As 28 days is longer than 1 week, this therefore reads on the construct of the instant claim.
Regarding claim 11: Following the discussion of claim 1, Neal et al further disclose the successful propagation of 128 unique PDOs, wherein blinded histological analysis of a subset of PDO cultures by a clinical pathologist identified the tumor subtype and grade of the original tumors with a 90% success rate (Paragraphs [0091]-[0092]). This success rate indicates that 90% of the original tumor cells within the PDOs are viable, meaning that the PDO tumor cells have a take rate of 90%. This therefore reads on the construct of the instant claim.
Regarding claim 13: Following the discussion of claim 1, Neal et al further disclose that tumor and immune cells of the PDO are embedded within a gel substrate. Neal et al note that the gel substrate is Matrigel (Paragraph [0024]), which is inherently a hydrogel. See Caliari et al, Page 8. This therefore reads on the construct of the instant claim.
Regarding claim 14: Following the discussion of claim 1, Neal et al further disclose that the tumor samples utilized to form the PDO have a total of 10 million cells (Paragraph [0030]). As this is comprised within the claimed range, this therefore reads on the construct of the instant claim. See MPEP § 2131.03.
Regarding claims 17-19: Following the discussion of claims 1 and 15, Neal et al further disclose that a plurality of PDOs in culture are contacted with a candidate agent of interest for a period of time sufficient to allow an effect on the cells within the PDO to be assessed, including an immunological response (claim 17) or anti-tumoral activity (claim 18). As the plurality of PDOs are cultured within growth medium prior to be contacted with the candidate agent (claim 19), this therefore reads on the methods of the instant claims.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 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.
Claims 1-6 and 8-19 are rejected under 35 U.S.C. 103 as being unpatentable over Neal et al (US 2018/0119107 A1, of record on IDS filed 03 June 2024) as evidenced by Janeway et al (Immunobiology: The Immune System in Health and Disease, 2001, of record on IDS filed 03 June 2024), National Cancer Institute (NCI Dictionary of Cancer Terms, 2018), and Caliari et al (Nat Methods, 2016, of record on IDS filed 03 June 2024).
The discussion of Neal et al regarding claim 1 can be observed above and is relied upon herein, the content of which is incorporated in its entirety. Neal et al as evidenced by Janeway et al, National Cancer Institute, and Caliari et al anticipate claims 1-6, 8-11, and 13-19.
Regarding claim 12: Following the discussion of claim 1 above, Neal et al further disclose that the PDO is cultured within growth medium for up to 28 days, and that the comprised tumor infiltrating lymphocytes survive for that time (Paragraphs [0017], [0073]-[0075], [0094]).
Neal et al do not disclose that the PDO comprises at least 75% live cells based on the average number of cells in the PDO at two weeks of culture, as required by instant claim 12.
However, it would have been prima facie obvious to have modified the PDO of Neal et al such that at least 75% of the cells are viable at two weeks of culture. One of ordinary skill in the art before the effective filing date of the invention would have been motivated to have a two-week PDO comprising at least 75% live cells, as it allows for a functional PDO that can be utilized for downstream assays, and would have recognized that it would have been a matter of routine optimization of the culture parameters to allow for such cell viability (Paragraphs [0012], [0092]; Figures 1E, 3A). See MPEP § 2144.05(II). Furthermore, the ordinary artisan would have had a reasonable expectation of success given that Neal et al provide culturing protocols to enhance the viability of the cells (Paragraph [0012]), and disclose that the PDOs can be cultured for at least 14 days. See MPEP § 2143(I)(G).
Consequently, Neal et al render obvious a PDO comprising at least 75% live cells based on the average number of cells in the PDO at two weeks of culture. This therefore renders obvious the construct of the instant claim.
Claims 1-19 are rejected under 35 U.S.C. 103 as being unpatentable over Neal et al (US 2018/0119107 A1, of record on IDS filed 03 June 2024) as evidenced by Janeway et al (Immunobiology: The Immune System in Health and Disease, 2001, of record on IDS filed 03 June 2024), National Cancer Institute (NCI Dictionary of Cancer Terms, 2018), and Caliari et al (Nat Methods, 2016, of record on IDS filed 03 June 2024), in view of Vinogradov et al (Nanomedicine (Lond), 2015, of record on IDS filed 03 June 2024).
The discussion of Neal et al regarding claim 1 can be observed above and is relied upon herein, the content of which is incorporated in its entirety. Neal et al as evidenced by Janeway et al, National Cancer Institute, and Caliari et al anticipate claims 1-6, 8-11, and 13-19. Neal et al as evidenced by Janeway et al, National Cancer Institute, and Caliari et al render obvious claims 1-6 and 8-19. Vinogradov et al is considered prior art under 35 USC 102(a)(1).
Regarding claim 7: As aforementioned in the discussion of claim 1 above, Neal et al disclose that the PDO is generated from a tumor biopsy containing the tumor cells and associated immune cells. Neal et al further disclose that the immune cells include macrophages (Paragraphs [0010], [0013], [0017], [0063], [0029]).
Neal et al do not disclose that the live tumor cells and the at least one type of live immune cell are present in the PDO in a ratio of about 1:1 to about 100:1, as required by instant claim 7.
However, Vinogradov et al disclose that tumor-associated macrophages form approximately 50% of the tumor mass (Abstract).
Therefore, it would have been prima facie obvious to have modified the PDO of Neal et al such that the macrophages are at a ratio of approximately 1:2 when compared to the amount of tumor cells, as taught by Vinogradov et al. One of ordinary skill in the art would have been motivated to generate a PDO that recapitulates tumors in vivo, and would have had a reasonable expectation of success given that Neal et al teach PDOs comprising tumor cells and macrophages. See MPEP § 2173(I)(G).
This consequently renders obvious the construct of the instant claim, as a roughly 2:1 ratio of tumor cell to macrophages lies within the range listed by Applicant and a prima facie case of obviousness exists in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art". In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990); In re Geisler, 116 F.3d 1465, 1469-71, 43 USPQ2d 1362, 1365-66 (Fed. Cir. 1997).
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 15-17 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 21-22 of copending Application No. 16/768963 in view of Neal et al (US 2018/0119107 A1, of record on IDS filed 03 June 2024) as evidenced by Janeway et al (Immunobiology: The Immune System in Health and Disease, 2001, of record on IDS filed 03 June 2024).
Although the claims at issue are not identical, they are not patentably distinct from each other because the copending claims anticipate and/or render obvious the instant claims. More specifically, the copending claims are not identical because no single copending claim discloses all of the limitations of any of the instant claims; however, each of the limitations of the instant claims are disclosed by separate copending claims, or rendered obvious by the accompanying prior art. The fact that each of the elements were claimed in the copending application, just not in a single claim, still renders obvious the instant invention because each of the features, though separately claimed, can be physically combined into a single embodiment.
Copending claim 1 is directed to an artificial mammalian skin construct, comprising: a first layer comprising live mammalian adipocytes and optionally live mammalian endothelial cells in a first hydrogel carrier; a second layer on or directly contacting said first layer, said second layer comprising live mammalian fibroblast cells, live mammalian follicle dermal papilla cells, and optionally live mammalian endothelial cells in combination in a second hydrogel carrier; and a third layer on or directly contacting said second layer, said third layer comprising live mammalian keratinocytes, live mammalian melanocytes, and live mammalian immune cells in combination in a third hydrogel carrier, wherein said construct has visible pigmentation after 3, 4, 5, 6, 7, or 8 weeks in culture.
As copending claim 1 is directed to an in vitro construct that comprises immune cells, this therefore anticipates instant claim 15.
With that, copending claim 21 is directed to a method of screening a compound or composition for activity when applied to the skin of a mammalian subject, comprising: providing the skin construct of claim 1 under conditions which maintain constituent cells of said construct alive; contacting said compound or composition to said construct; and then detecting a response of said skin construct, the presence of such response indicating said compound or composition is potentially active if applied to the skin of a mammalian subject.
As copending claim 22 further defines the response as an immune response, this therefore renders obvious the method of instant claim 17.
Instant claim 16 is known from the prior art and can be further incorporated into the in vitro construct anticipated by copending claim 1:
Neal et al as evidenced by Janeway et al teach the limitation recited in instant claim 16.
This is a provisional nonstatutory double patenting rejection.
Claims 1-19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5, 8-9, and 14 of U.S. Patent No. 11,959,095 B2 in view of Neal et al (US 2018/0119107 A1, of record on IDS filed 03 June 2024) as evidenced by Janeway et al (Immunobiology: The Immune System in Health and Disease, 2001, of record on IDS filed 03 June 2024) and National Cancer Institute (NCI Dictionary of Cancer Terms, 2018).
Although the claims at issue are not identical, they are not patentably distinct from each other
because the patented claims render obvious the instant claims. More specifically, the patented claims are not identical because no single patented claim discloses all of the limitations of any of the instant claims; however, each of the limitations of the instant claims are rendered obvious by the accompanying prior art.
Patent claim 1 is directed to an artificial cell construct comprising: a core comprising glioblastoma cells and a first population of non-cancerous tissue cells that comprises glial cells, wherein the glioblastoma cells and the first population of non-cancerous tissue cells are intermixed with one another; and a shell comprising a second population of non-cancerous tissue cells that comprises endothelial cells, wherein the shell surrounds the core.
Patent claim 1 does not disclose that the artificial cell construct comprises immune cells, as required by instant claim 1.
Neal et al, however, disclose in vitro culture systems of human solid tumors as three-dimensional patient derived organoids (PDO) that recapitulate the cellular architecture and ultrastructure of the tumor sample from which they were derived, and include immune cells, parenchymal and stromal elements (Paragraphs [0010], [0020], [0028], [0090]-[0095]). As such, Neal et al disclose PDOs comprising glioblastoma cancer cells (Paragraph [0063]).
Therefore, it would have been prima facie obvious to have modified the artificial cell construct of patent claim 1 such that it further comprises immune cells, as detailed in Neal et al. One of ordinary skill in the art before the effective filing date of the invention would have been motivated to include immune cells within the artificial cell construct, as it better recapitulates the microenvironment of in vivo tumors (Neal et al: Paragraphs [0004]-[0007], [0019]), and would have had a reasonable expectation of success given that the patented claims and disclosure of Neal et al are concerned with the generation of in vitro cell constructs comprising glioblastoma cells. See MPEP § 2143(I)(G).
Consequently, patent claim 1 as modified by Neal et al render obvious an artificial cell construct comprising glioblastoma cells and immune cells. This therefore renders obvious the in vitro cell construct of instant claims 1 and 15.
With that, instant claims 2-14 and 16-19 are known from the prior art and can be further incorporated into the artificial cell construct rendered obvious by patent claim 1 as modified by Neal et al:
Patent claims 5, 8-9, and 14 teach the limitations recited in instant claims 7, 9, 13, and 17-18.
Neal et al as evidenced by Janeway et al and National Cancer Institute teach the limitations recited in instant claims 2-6, 8, 10-12, 14, 16, and 19.
Conclusion
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/ALYSSA G WESTON/Examiner, Art Unit 1633
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