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
Claims 1-5, 11, 12, 15, 17, 21, 26, 34, 38, 40, 41, 47, 51, and 55-62 are pending.
Claim 27 is canceled.
Claims 15, 26, 51, 55, and 59 are currently amended.
Claims 1-5, 11, 12, 15, 17, 21, 26, 27, 34, 38, 40, 41, 47, 51, and 55-62 are under examination on the merits.
Rejections Maintained
35 U.S.C. 103
The rejection of claims 21, 34, 38, and 60-62 under 35 U.S.C. 103 as being unpatentable over Fikes et al. (WO 01/41741, international publication date: 06/14/2001) is maintained.
The rejection of claims 26, 27, 40, 41, and 47 under 35 U.S.C. 103 as being unpatentable over Fikes et al. (WO 01/41741, international publication date: 06/14/2001), as applied to claims 21, 34, 38, and 60-62, and further in view of Chan et al. (WO 2016/081947, international publication date: 05/26/2016, in IDS from 12/06/2021) is maintained.
Response to Arguments
In Applicant Arguments, dated 01/08/2026, Applicant asserts that “Fikes' teachings are inapposite of the claimed subject matter - Fikes actually treats subjects who lost heterozygosity. Fikes describes vaccine compositions having at least one peptide from an oncogene (e.g., CEA, HER2/neu, MAGE2, MAGE3, or p53). See, Fikes at Abstract. As quoted by the Examiner, Fikes states that ‘[o]ne of the most common types of alterations in class I molecules is the selective loss of certain alleles in individuals heterozygous for HLA.’ See, Fikes at page 39, lines 31-32, emphasis added. Therefore, Fikes describes a formerly heterozygous patient becoming homozygous through the loss of an HLA allele. Fikes describes that this loss of heterozygosity is a tumor adaptation in response to immune pressure, and that ‘[t]his type of alteration allows the tumor to retain class I expression and thus escape NK cell recognition.’ See, Fikes at page 39, lines 34-35. However, Fikes describes their invention as taking advantage of this HLA allele loss, such that the cancers are ‘still [] susceptible to a CTL-based vaccine in accordance with the invention which comprises epitopes corresponding to the remaining HLA type.’ See, Fikes at page 39, lines 34-36, emphasis added. A person skilled in the art would clearly recognize that Fikes is describing the advantages of methods of treating a subject with a loss of heterozygosity. In sharp contrast, the claimed method recites, in relevant part, administering an immunotherapy agent to a subject with a tumor who displays HLA class I heterozygosity.”
These arguments have been fully considered but are not deemed persuasive. At p. 41, Fikes et al. teach that “[t]he frequency of alterations in class I expression is the subject of numerous studies... Rees and Mian estimate allelic loss to occur overall in 3-20% of tumors, and allelic deletion to occur in 15-50% of tumors. It should be noted that each cell carries two separate sets of class I genes, each gene carrying one HLA-A and one HLA-B locus. Thus, fully heterozygous individuals carry two different HLA-A molecules and two different HLA-B molecules. Accordingly, the actual frequency of losses for any specific allele could be as little as one quarter of the overall frequency. They also note that, in general, a gradient of expression exists between normal cells, primary tumors and tumor metastasis. In a study from Natali and coworkers…, solid tumors were investigated for total HLA expression, using W6/32 antibody, and for allele-specific expression of the A2 antigen, as evaluated by use of the BB7.2 antibody. Tumor samples were derived from primary cancers or metastasis, for 13 different tumor types, and scored as negative if less than 20%, reduced if in the 30-80% range, and normal above 80%. All tumors, both primary and metastatic, were HLA positive with W6/32. In terms of A2 expression, a reduction was noted in 16.1 % of the cases, and A2 was scored as undetectable in 39.4 % of the cases. Garrido and coworkers … emphasize that HLA changes appear to occur at a particular step in the progression from benign to most aggressive. Jiminez et al … have analyzed 118 different tumors (68 colorectal, 34 laryngeal and 16 melanomas). The frequencies reported for total loss of HLA expression were 11% for colon, 18% for melanoma and 13 % for larynx. Thus, HLA class I expression is altered in a significant fraction of the tumor types, possibly as a reflection of immune pressure, or simply a reflection of the accumulation of pathological changes and alterations in diseased cells.”
Based upon these teachings, one of ordinary skill in the art would appreciate that in many cancers, the expression of certain HLA alleles, such as the A2 antigen, is reduced, and it is thought that these “[a]llele-specific alterations might reflect the tumor adaptation to immune pressure, exerted by an immunodominant response restricted by a single HLA restriction element. This type of alteration allows the tumor to retain class I expression and thus escape NK cell recognition.” See p. 39 of Fikes et al. Natali and colleagues demonstrated that for several different cancer types, expression of A2 was reduced (16.1% of cases) or undetectable (39.4% of cases). As such some cancer types will demonstrate a loss of HLA class I hererozygosity, while other cancer types will not demonstrate a loss of HLA class I hererozygosity; however one of ordinary skill in the art would appreciate that, in either case, cancer therapy is warranted. Therefore Applicant’s assertion that “Fikes' teachings are inapposite of the claimed subject matter” is not deemed persuasive.
Allowable Subject Matter
Claims 51 and 59 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
Claims 1-5, 11, 12, 15, 17, and 55-58 are allowed.
THIS ACTION IS MADE FINAL. 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 extension fee 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.
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/NELSON B MOSELEY II/Primary Examiner, Art Unit 1642