Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
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.
DETAILED ACTION
Claims 4-5, 7-11, and 18-29 are pending in the instant application.
Priority
This application is a Continuation of Application 17/007415 (now US11859015), filed on 8/31/2020, which is a Div of 15/920335 filed on 3/13/2018, which is a CIP of 14/760997 filed on 7/14/2015, which claims priority to PCT/US14/11711 filed on 1/15/2014 and on the provisional application 61752799 filed on 1/15/2013.
Objections to the Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code on pg 26, para 0082; and pg 66, para 0246; . Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Correction is required. See MPEP § 608.01(b).
Objections to the Claims
Claim 4 uses language that is inconsistent with the other claims (e.g. claims 7-8). Please replace “sequence selected from among SEQ ID NO:” with “selected from the group consisting of SEQ ID NO:”.
Claim 10’s inclusion of multiple conjunctions within option (a) adds confusion to the claim. Please replace “(a) one or more isolated peptides of claim 4 or a pharmaceutical composition thereof, and (b) an adjuvant” with “(a) one or more isolated peptides of claim 4; and (b) an adjuvant”. Note the semicolon greatly reduces confusion regarding what selections are to be made.
Claim 11 lacks an explanation for the acronym “BCG”. Please replace “BCG” with “BCG (Bacille Calmette Guerin)” according to the definition supplied in the instant specification on pg 63, para 0232.
Claim 18, in order to delineate list items, please replace “cell and (b)” with “cell; and (b)”.
Correction is required. See MPEP § 608.01(m).
Claim Rejections – 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 19-21, 22-24, and 25-27 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for:
(i) a method of treating a WT1-expressing cancer; (ii) reducing incidence of a WT1-expressing cancer; or (iii) reducing relapse of a WT1-expressing cancer using any peptide consisting of SEQ ID NOs: 8-9, 12-13, 18, 21, 30-33, 35-39, 41-44, 46-50, 55, and 63;
It does not reasonably provide enablement for:
(i) a method of treating a WT1-expressing cancer; (ii) reducing incidence of a WT1-expressing cancer; or (iii) reducing relapse of a WT1-expressing cancer using any peptide comprising SEQ ID NOs: 8-9, 12-13, 18, 21, 30-33, 35-39, 41-44, 46-50, 55, and 63.
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
Claims 19-21, 22-24, and 25-27
Attention is directed to In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 where the court set forth the eight factors to consider when assessing if a disclosure would have required undue experimentation. Citing Ex parte Forman, 230 USPQ 546 (BdApls 1986) at 547 the court recited eight factors: (1) the nature of the invention; (2) the state of the prior art; (3) the relative skill of those in the art; (4) the predictability or unpredictability of the art; (5) the breadth of the claims; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary.
All of the Wands factors have been considered with regard to the instant claims, with the most relevant factors discussed below.
Nature of the invention/Breadth of claims:
The claims are drawn to (i) a method of treating a WT1-expressing cancer; (ii) reducing incidence of a WT1-expressing cancer; or (iii) reducing relapse of a WT1-expressing cancer using any peptide comprising SEQ ID NOs: 8-9, 12-13, 18, 21, 30-33, 35-39, 41-44, 46-50, 55, and 63.
State of the prior art/Predictability or unpredictability of the art:
The structure of antigenic peptides is unpredictable and suspected candidates must be screened in order to determine which are effective in treating cancer. Nguyen (US11421016, SEQ ID NOs: 1-1,408,729) teaches small cancer neoepitopes which are able to be presented by major histocompatibility complex class I (MHC-I) molecules (col 4, para 2) in order to elicit an immune response toward cancer cells of a subject. Importantly, Nguyen teaches that not every peptide elicits an immune response (col 3, para 1), thus to arrive at effective neoantigen peptides, several screens were performed to select peptides with sufficient binding affinity, sufficient strength of expression, and proper sub-cellular location (col 2, para 5).
Similarly, Engelhard (doi: 10.1146/annurev.iy.12.040194.001145) teaches MHC class I/II molecules bind a wide variety of peptides (pg 186, para 1). Engelhard teaches the structural features commonly exhibited in antigenic peptides that bind class I molecules, however the structural irregularities make prediction difficult (pg 188, para 2; pg 189, Table 1). Engelhard teaches most antigenic peptides are 12-19 residues in length, whereas a range of 10-30 has been observed (pg 194, para 1).
Amount of guidance/Existence of working examples:
In order to verify which of the antigenic peptides (a) bound to an MHC molecule and (b) producing an anti-cancer antigenic effect, applicant conducted a series of screens (Examples 2-6). Applicant performed computational studies to find peptides that were most likely to bind to an MHC molecule (Examples 7-9). Only in Example 10, did applicant test whether the peptide induced the desired response. In applicant’s own words:
“While many sequences can be predicted by the algorithms, these models do not predict binding to MHC when tested on live cells in 30% of cases (Gomez-Nunez et al. Leuk Res. 2006;30(10): 1293-8), therefore in vitro testing is necessary. In addition, even if binding is demonstrated, a cytotoxic T cell response may not occur, requiring additional in vitro study.” (instant spec; pg 66-67, para 0246).
Quantity of experimentation:
Given the unpredictability of which peptides can (a) bind to an MHC molecule AND (b) produce an anti-cancer antigenic effect sufficient for a treatment and vaccine, one of skill in the art, in undertaking the experimentation necessary to determine which of the claimed peptide variants could achieve (a) and (b) would have no reasonable expectation that the majority of peptide claimed would be successful in treating WT1-expressing cancers. One of skill in the art would have to undergo undue experimentation to verify which permutations of peptides that comprise these sequences are able to be used as an effective anti-cancer vaccine.
Lack of a working example is a critical factor to be considered, especially in a case involving an unpredictable and undeveloped art. See MPEP § 2164.
See the decision in Rasmusson v. SmithKline 413 F.3d 1318, 1325 (Fed. Cir. 2005) which stated: “Thus, at the end of the day, the specification, even read in the light of the knowledge of those skilled in the art, does no more than state a hypothesis and propose testing to determine the accuracy of that hypothesis. That is not sufficient. [Citation omitted.] ‘If mere plausibility were the test for enablement under §112, applicants could obtain patent rights to “inventions” consisting of little more than respectable guesses as to the likelihood of their success. When one of the guesses later proved true, the “inventor” would be rewarded the spoils instead of the party who demonstrated that the method actually worked.’”
Therefore, in view of the Wands factors as discussed above, e.g., the amount of guidance provided, the predictability of the art and the lack of working examples, to practice the full scope of the claimed invention herein, a person of ordinary skill in the art would have to engage in undue experimentation, with no assurance of success.
Claim Rejections – 35 USC § 102/103
The following is a quotation of the appropriate paragraphs of pre-AIA 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) the invention was known or used by others in this country, or patented or described in a printed publication in this or a foreign country, before the invention thereof by the applicant for a patent.
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter 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 pre-AIA 35 U.S.C. 103(a) 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.
Claims 4-5, 7-11, and 18-29 rejected under pre-AIA 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under pre-AIA 35 U.S.C. 103(a) as obvious over Brix (US20110318380).
Claim 4-5, 8
Regarding claims 4-5 and 8, Brix teaches an isolated peptide consisting of the sequence SEQ ID NO: 8 (SEQ ID NO: 18845), shown below.
instant_8 CMTWNQMNLGATLKG 15
Brix_18845 CMTWNQMNLGATLKG 15
***************
Brix teaches the peptide is a cancer antigenic peptide that binds to an MHC class I/II molecule (pg 1, para 0010). Because the structure of Brix’s peptide (SEQ ID NO: 18845) satisfies the same structural requirements as instantly claimed, it must necessarily bind an MHC class II molecule, as a chemical composition and its properties are inseparable. See MPEP § 2112.01(II). Brix teaches administering the peptide or peptide composition to an individual in need thereof an effective amount of the peptide or peptide composition as a means of vaccinating said individual against cancer (pg 3, para 0034).
Claim 7
Regarding claim 7, Brix teaches an antigenic peptide that binds to an MHC class I/II molecule comprising SEQ ID NO: 42 (SEQ ID NO: 18293), shown below.
instant_42 QFPNHSFKHEDPM- 13
Brix_18293 QFPNHSFKHEDPMG 14
*************
Because the structure of Brix’s peptide (SEQ ID NO: 18293) satisfies the same structural requirements as instantly claimed, it must necessarily bind an MHC class I molecule, as a chemical composition and its properties are inseparable. See MPEP § 2112.01(II).
Claim 9
Regarding claim 9, Brix teaches a composition comprising the peptide and a pharmaceutically acceptable carrier (pg 62, para 1087-1088).
Claim 10-11
Regarding claims 10-11, Brix teaches a vaccine composition comprising the peptide and an adjuvant, such as alum (pg 59, para 1007-1012).
Claim 18
Regarding claim 18, Brix teaches generating a cancer vaccine composition comprising antigen presenting cells presenting the antigenic peptides of the invention (pg 64, para 1123-1126).
Claim 19-21
Regarding claims 19-20, Brix teaches the peptides or compositions thereof are effective in treating acute myeloid leukemia and Wilm’s Tumor (pg 41, para 0708-0709) which expresses WT1 (Wilms Tumor 1). As an evidentiary reference, Sugiyama (doi: 10.1093/jjco/hyp194) teaches WT1 was isolated as the gene responsible for Wilm’s tumor (pg 377, col 1, para 1). Sugiyama also teaches that WT1 is highly expressed in the majority of acute myeloid leukemias (pg 377, col 1, para 2).
Claim 22-24
Regarding claims 22-24, Brix teaches the vaccine composition comprising the peptide of the invention can prevent the cancer from occurring when administered prophylactically (pg 57, para 0934-0936; pg 39, para 0686). Thus satisfying the limitation of “reducing an incidence of a WT1-expressing cancer”.
Claims 25-27
Regarding claims 25-27, Brix teaches the vaccine composition comprising the peptide of the invention can prevent the cancer from recurring (pg 57, para 0936; pg 39, para 0682). Thus satisfying the limitation of “reducing relapse of a WT1-expressing cancer”.
Claim 28
Regarding claim 28, Brix teaches the cancer is Wilms’ tumor (pg 41, para 0708-0709).
Claim 29
Regarding claim 29, Brix teaches the cancer is mesothelioma (pg 41, para 0708).
No Double Patenting Rejections Made
The instant application is a Continuation of Application 17/007415 (now US11859015), which is a Div of 15/920335 (now US10815273), which is a CIP of 14/760997 (now US9919037). No double patenting rejections were made because:
The instant application is drawn to SEQ ID NOs: 8-9, 12-13, 18, 21, 30-33, 35-39, 41-44, 46-50, 55, 63;
US11859015 claims peptides comprising SEQ ID NOs: 7, 10-11, 19-20, 23;
US10815273 claims a nucleic acid encoding SEQ ID NOs: 6, 14-17, 22; and
US9919037 claims peptides consisting of SEQ ID NOs: 6, 14-17, 22.
Because the claims do not encompass overlapping subject matter, no double patenting rejection was made.
Relevant Prior Art
Pietersz (doi: 10.2174/092986706777441922) teaches methods of generating antigenic peptides and suitable adjuvants to be used as anti-cancer vaccines.
Not Allowable Over the Prior Art
The isolated peptides consisting of SEQ ID NOs: 8, 39, and 49-50 were found in the prior art (see US20110318380), thus are not allowable as described in the 102/103 rejection above.
Allowable Subject Matter
The isolated peptides comprising or consisting of the sequences of SEQ ID NOs: 18, 30-33, 35-37, 41, 43, 46-48, 55, and 63 were not found in the prior art. However note that sequences comprising these sequences are not allowable in (i) a method of treating a WT1-expressing cancer; (ii) reducing incidence of a WT1-expressing cancer; or (iii) reducing relapse of a WT1-expressing cancer due to the unpredictability of anti-cancer antigenic peptides as described in the 112(a) rejection above.
The isolated peptides consisting of the sequences of SEQ ID NOs: 9, 12-13, 21, 39, 42, and 44 were not found in the prior art.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAURA ANN ESSEX whose telephone number is 571-272-1103. The examiner can normally be reached Mon - Fri 8:30-5:00.
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/L.A.E./
Examiner, Art Unit 1675
/JEFFREY STUCKER/
Supervisory Patent Examiner, Art Unit 1675
