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 .
Restrictions/Elections
Applicant’s election of the following invention/species without traverse, as set forth in the Reply filed 07 July 2025, is acknowledged:
Group 14: claim 14 and claim 16(n) directed to an isolated anti-RET monoclonal antibody or antigen binding fragment thereof comprising the HCVR/LCVR sequence pair of SEQ ID NO: 210/218, and claim 15(n) directed to the HCDR1-3 of SEQ ID NOs: 212, 214, and 216, respectively, and the LCDR1-3 of SEQ ID NOs: 220, 222, and 224.
Status of the Claims
Claims 14-16 and 18-42 are currently pending and are subject to this Office Action. This is the first Office Action on the merits of the claims.
Information Disclosure Statement
The references cited on the information disclosure statement(s) were considered and have been made of record.
Claim Interpretation
The recitation of “the RET receptor tyrosine kinase gene, or a rearranged form thereof” is interpreted as including any isoform of RET protein.
Withdrawn Claim Rejections
In view of Applicant’s claim amendments, the rejection of claims 21-33 and 36-40 under 35 U.S.C. 112(a) are hereby withdrawn.
Maintained 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 14-16 and 18-20 stand/are rejected under 35 U.S.C. 101 because the claimed invention is directed to a product of nature without significantly more.
The claims recite an antibody with the sequences of clone H4H8079P with HCVR and LCVR sequences set forth in SEQ ID NOs: 210 and 218, and VL-CDR1-3 and HCDR1-3 set forth in SEQ ID NOs: 212, 214, and 216, LCDR1-3 set forth in SEQ ID NOs: 220, 222, and 224. Clone H4H8079P was isolated directly from antigen-positive B cells without fusion to myeloma cells1. Therefore, the sequences which bind to RET that are obtained from clone H4H8079P are a product of nature (MPEP 2106.04(b)(II), Step 2A, prong one).
When a law of nature or natural phenomenon is claimed as a physical product, the courts have often referred to the exception as a "product of nature". For example, the isolated DNA of Myriad and the primers of Ambry Genetics were described as products of nature by the courts. Ass’n for Molecular Pathology v. Myriad Genetics, Inc., 569 U.S. 576, 580, 106 USPQ2d 1972, 1975 (2013); University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 758-59, 113 USPQ2d 1241, 1243 (Fed. Cir. 2014).
As the Supreme Court made clear, neither naturally occurring compositions of matter, nor synthetically created compositions that are structurally identical to the naturally occurring compositions, are patent eligible."). Thus, a synthetic, artificial, or non-naturally occurring product such as a cloned organism or a human-made hybrid plant is not automatically eligible because it was created by human ingenuity or intervention. See, e.g., In re Roslin Institute (Edinburgh), 750 F.3d 1333, 1337, 110 USPQ2d 1668, 1671-72 (Fed. Cir. 2014) (cloned sheep); cf. J.E.M. Ag Supply, Inc. v. Pioneer Hi-Bred Int’l, Inc., 534 U.S. 130-132, 60 USPQ2d 1868-69 (2001) (hybrid plant).
In Myriad, the Supreme Court also made clear that not all changes in characteristics will rise to the level of a marked difference, e.g., the incidental changes resulting from isolation of a gene sequence are not enough to make the isolated gene markedly different. Myriad, 569 U.S. at 580, 106 USPQ2d at 1974-75. Therefore, the acts of generating antibodies from a clone directly isolated from antigen-positive B cells without fusion to myeloma cells, even if providing incidental changes resultant from isolation, cloning, and selection, do not produce markedly different characteristics over the naturally occurring antibody sequences.
The claims that specifically recite/encompass the natural product of H4H8079P antibody sequences (elected matter) are claims 14-16 and 18-20.
This judicial exception is not integrated into a practical application because there are no additional elements linking the product of nature to a practical application, e.g. to effect a particular treatment or prophylaxis (Step 2A, prong two; MPEP 2106.04(d)).
The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because no additional elements beyond the described product(s) of nature are described in the claims (Step 2B; MPEP 2106.05).
Priority
As stated in the previous Office Action, the earliest effective U.S. filing date afforded the instantly claimed invention has been determined to be 10 April 2019, the filing date of Provisional Application No. 62/832,218, to which Int. Application No. PCT/US2020/027554 claims priority to.
Allowable Subject Matter
Claims 21-42 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.
Response to Arguments
Applicant's arguments, filed 22 December 2025, have been fully considered but they are not persuasive. Applicable arguments pertaining to maintained rejections are addressed below.
It is the Examiner’s understanding that Applicant is alleging that the antibody designated H4H8079P is not the product of natural immunological processes in humans, and thus, is not a product of nature. However, RET is expressed in humans, and has been identified as a potential therapeutic target due to its expression in in human breast cancer cell lines (see instant specification at para. [0003] to [0006]). While the antibodies of the present application were developed through human intervention (i.e., lab-produced in transgenic mice), there is no evidence that the claimed variable region sequences are structurally different to those of naturally occurring anti-RET antibodies directed to RET in the human body. As the Supreme Court made clear, neither naturally occurring compositions of matter, nor synthetically created compositions that are structurally identical to the naturally occurring compositions, are patent eligible."). Thus, a synthetic, artificial, or non-naturally occurring product such as a cloned organism or a human-made hybrid plant is not automatically eligible because it was created by human ingenuity or intervention. See, e.g., In re Roslin Institute (Edinburgh), 750 F.3d 1333, 1337, 110 USPQ2d 1668, 1671-72 (Fed. Cir. 2014) (cloned sheep); cf. J.E.M. Ag Supply, Inc. v. Pioneer Hi-Bred Int’l, Inc., 534 U.S. 130-132, 60 USPQ2d 1868-69 (2001) (hybrid plant).
In response to Applicant’s argument that the genome of this VELOCIMMUNE® transgenic mouse comprises human heavy- and light-chain variable regions operably linked to endogenous mouse constant-region loci, allowing the mouse to produce antibodies with human variable regions and mouse constant regions in response to antigenic stimulation, the claims are drawn to human heavy- and light-chain variable regions.
In response to Applicant’s argument that human heavy- and light-chain variable regions the Office has not provided any evidence that a naturally occurring human antibody to RET exists, nor has it identified any naturally occurring counterpart with the same sequence as the antibody designated H4H8079P, given that the antibody designated H4H8079P binds to human RET and has human variable regions, it would be likely that antibodies with human variable regions that bind human RET would occur naturally. Applicant has not sufficiently demonstrated why naturally occurring antibodies comprising the listed human variable regions would not exist in nature.
Conclusion
Claims 14-16 and 18-20 are rejected. Claims 21-42 are objected to.
THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action. Any inquiry concerning this communication or earlier communications from the examiner should be directed to LEA S O'BRIEN whose telephone number is (703)756-4793. The examiner can normally be reached Monday - Friday 5:00AM - 2:30PM PT.
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/LEA S O'BRIEN/Examiner, Art Unit 1646
/MARK HALVORSON/Primary Examiner, Art Unit 1646
1 See instant specification, para. [0184].