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. Election/Restrictions Applicant’s election without traverse of the species SEQ ID NO: 8 in the reply filed on 2/17/2026 is acknowledged. The Examiner further notes that all other species have now been cancelled. The election species reads on claims 21-40. Claim Status Claims 21-40 are pending and under examination in the instant office action. Claim Rejections - 35 USC § 112(b) 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 appl icant regards as his invention. Claims 24 , 25 , 28, 33 and 40 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. Claims 24 and 25 are rejected for recitation of intended result/effect without conferring some structural, material, or manipulative difference on the scope of the claim. Claims 24 recites the compound “wherein the K D and/or k off is assessed using surface plasmon resonance” and claim 25 recites wherein the SPR uses human FOLR1 as an immobilized ligand. It is unclear whether or not assessing the binding affinity of the antibody via SPR is required for infringement because methodology is implicit but the claims are directed towards a compound but the limitations appear to recite methods steps . Absent specific structure or function that would be conferred by the method , it is unclear how these claims further limit the scope of the parent claim. MPEP 2173.05(g) states: “the use of functional language in a claim may fail ‘to provide a clear-cut indication of the scope of the subject matter embraced by the claim' and thus be indefinite.” It further states: “Examiners should consider the following factors when examining claims that contain functional language to determine whether the language is ambiguous: (1) whether there is a clear cut indication of the scope of the subject matter covered by the claim; (2) whether the language sets forth well-defined boundaries of the invention or only states a problem solved or a result obtained; and (3) whether one of ordinary skill in the art would know from the claim terms what structure or steps are encompassed by the claim” (emphasis added). Since the claims fail to meet all (3) criteria set forth in MPEP 2173.05(g), then Claims 24 and 25 are rejected. Regarding claim 28, the parenthetical “positron-emitting radioisotopes (PET)” and “γ-emitting radioisotopes (SPECT)” renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention; “PET” and “SPECT” are not abbreviations for the limitations positron-emitting radioisotopes or γ-emitting radioisotopes so it is unclear what is meant by the parenthetical. See MPEP § 2173.05(d). It is suggested the applicant delete the limitations in parentheses. Claim 33 recites “wherein said linker comprises N-succinimidyl-4-guanidinomethyl-3-[I-131]iodobenzoate or a derivative thereof”. The metes and bounds of the claim are unclear because the compound already requires an iodine-131 radionuclide as recited in claim 30, and the linker and the radionuclide are distinct as recited in claim 31. Therefore, it is unclear whether two copies of I-131 are required by the claim or if N-succinimidyl-4-guanidinomethyl-3-[I-131]iodobenzoate describes both the linker and radionuclide together. The examiner suggests amending the claim to read “wherein said linker and said radionuclide comprises N-succinimidyl-4-guanidinomethyl-3-[I-131]iodobenzoate ”. Regarding claim 40, the claim is indefinite for the recitation of “a new method”. The term “new” is a relative term and the specification does not provide guidance or definition to determine the newness of the method. It is uncertain if the newness is assessed relative to the patent filing or the moment the claim is being read. The examiner suggests amending the claim to strike the word “new”. Claim Rejections - 35 USC § 112(a) - Written Description 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 21-40 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. Scope of the claimed genus The instant claims are directed towards an antibody or fragment thereof that specifically binds to an epitope of FOLR1 but does not bind to FOLR2 or FOLR3, said VHH being linked to a radionuclide and wherein the VHH comprises an amino acid having at least 63% identity to SEQ ID NO: 8 over the full length of said sequence or over 50% of said sequence . First, the scope is directed towards an antibody or fragment thereof, where both the antibody and the fragment thereof are limited by the functional limitation of specifically binding to FOLR1 but not FOLR2 or FOLR3; however, only the VHH is required to comprise an amino acid sequence having at least 63% identity over 50% or the full length of SEQ ID NO: 8. Regarding fragments, the specification states “Parts, fragments or analogs retaining (at least part of) the functional activity, and/or retaining (at least part of) the binding specificity of the original heavy chain variable domain of an antibody from which these parts, fragments or analogs are derived from are also further referred to herein as ‘functional fragments’ of a heavy chain variable domain” (p. 54 lines 25-29); “For example, the invention provides a number of stretches of amino acid residues (i.e. small peptides), also referred to herein as CDR sequences or part of the antibody fragment as identified as SEQ ID NO, such as sequences having at least 60% identity with at least one of SEQ ID NO: 2, 3, 4,5, 6, 7, 8, 9, 10, 11, 12, 17, 18, 19, 25, 26, 27, 33, 34, 35, 41, 42, 43 of the antibody fragment, preferably VHH’s as disclosed herein” (p. 56 lines 25-29). Therefore, the claims are also directed at smaller fragments of a VHH with 63% identity over 50% of the length of SEQ ID NO: 8, wherein the fragment is does not need to be any particular length, it must only preserve part of the functional limitation s of the parent VHH as claimed . Further, the limitations towards 63% identity over 50% of the length of the VHH allows for changes to the binding-determinant CDR regions of the instant VHH antibodies. Claim 22 is directed towards wherein said VHH comprises SEQ ID NO: 8 or SEQ ID NO: 12. However, the claim still does not require that the fragment comprise all of SEQ ID NO: 8 or SEQ ID NO: 12; additionally, comprising SEQ ID NO: 12 is only directed towards the CDR3 and allows for changes to the other binding-determinant CDRs. Claims 23 through 25 define additional functional limitations in regards to the binding affinity of the VHH or fragment thereof to human FOLR1, but they do not specify a particular structure that conveys the claimed binding-affinity function. Claims 26 through 30 are directed towards particular radionuclides but do not limit the structure of the antibody or antibody fragment. Claims 31 through 33 are directed towards particular linkers linked the VHH and the radionuclide but do not limit the structure of the antibody or antibody fragment. Regarding claim 33, the claim recites that the linker is N-succinimidyl-4-guanidinomethyl-3-[I-131]iodobenzoate or a derivative thereof . Claims 34 through 40 are directed towards pharmaceutical compositions, diagnostic compositions, and methods of treatment comprising the VHH compound or pharmaceutical compositions but do not further limit the structure of the antibody or antibody fragment. State of the Relevant Art It is well established in the art that the formation of an intact antigen-binding site in an antibody usually requires the association of the complete heavy and light chain variable regions of a given antibody, each of which comprises three CDRs (or hypervariable regions) which provide the majority of the contact residues for the binding of the antibody to its target epitope. E.g., Almagro et. al., Front. Immunol. 2018; 8:1751 (see Section “The IgG Molecule” in paragraph 1 and Figure 1). While affinity maturation techniques can result in differences in the CDRs of the antibody compared to its parental antibody (page 3 “The IgG Molecule, second and third paragraphs), those techniques involve trial-and-error testing and the changes that maintain or improve affinity are not predictable a priori . E.g., id. , (page 6 ending paragraph onto page 7). Chiu ML et al. (Antibodies 2019 8, 55, 1-80) taught the antigen binding of antibodies often results in conformational changes in the contact surface areas of both the antibody and the antigen (page 5, first paragraph). Thus, the prediction of CDR binding to the epitope is difficult to predict. Chiu further taught antibody modeling has been shown to be accurate for the framework region sequences, but CDR modeling requires further development and improvements (page 6, second paragraph). Prediction of the structure of HCDR3 could not be accurately produced when given the Fv structures without their CDR-H3s (page 6, second paragraph). Chiu taught the quality of antibody structure prediction, particularly regarding CDR-H3, remains inadequate, and the results of antibody–antigen docking are also disappointing (page 11, paragraph 2) . For a single-domain antibody, the structure of single-domain antibodies and antibody variable domains composed of a single-domain heavy chain (VHH) is known in the art and requires the association of three complete CDRs . As taught by Noël et. al. "Global analysis of VHHs framework regions with a structural alphabet." Biochimie 131 (2016): 11-19 , VHH domains are the variable regions of Heavy Chain Antibodies ( HCAbs ), which are immunoglobulin proteins lacking a light chain and a CH1 domain. Noël et. al. teaches: “ These VHHs are composed of 4 regions whose sequences and structures are defined as conserved (called Framework Regions , FRs ). In addition, VHHs contain three connecting regions showing high variability both in sequence content and structure conformation. These regions are complementary to the antigen surface and are called Complementarity Determining Regions or CDRs). Fig. 1 underlines in 3D (see Fig. 1A [8] , [9] , [10] , HYPERLINK "https://www.sciencedirect.com/science/article/pii/S0300908416301729" \l "bib11" [11] , HYPERLINK "https://www.sciencedirect.com/science/article/pii/S0300908416301729" \l "bib12" [12] , HYPERLINK "https://www.sciencedirect.com/science/article/pii/S0300908416301729" \l "bib13" [13] , HYPERLINK "https://www.sciencedirect.com/science/article/pii/S0300908416301729" \l "bib14" [14] , HYPERLINK "https://www.sciencedirect.com/science/article/pii/S0300908416301729" \l "bib15" [15] , HYPERLINK "https://www.sciencedirect.com/science/article/pii/S0300908416301729" \l "bib16" [16] ) and 2D (see Fig. 1 B) similarities of VHHs to conventional antibodies ” (Introduction, 3 rd para. and Fig. 1). Noël et. al. teaches that the framework regions (FRs) of VHHs are considered to be “constant” regions with a conserved structure, and in some cases a conserved sequence. The FR identity ranged from 76.9% for FR2 to 94.4% for FR4, and the whether there was variation in the amino acids was constrained to particular positions (Fig. 2). In particular, there is a structural pattern that is conserved in the FRs, suggesting that these are not dispensable for antigen-binding function: “ Each of the four FRs is associated to a main structural pattern, which can be considered as canonical, but represents only 40, 84, 63, and 38%, leading to the characterization to variant patterns ranging from 6 to 19. Among some of them, we observe some similarity and the final number of variant patterns could be slightly reduced. However, clearly some are really outliers at more than 1 Å from the main structural pattern and could have strong impact of the proposition of structural models ” (Discussion, 6 th para.). The CDRs of the VHH interact with framework sequences. These interactions would vary between CDR sequences and changes to the framework sequences would change these interactions resulting in changes to the structure and activity of the VHH ( Rouet et. al. Journal of Biological Chemistry. 290(198):11905-11917 (2015) (Abstract, Figures 5-7). Rouet further teaches that variation in the CDR sequences change the stability of VHH when humanizing a VHH so a consensus framework region of a VHH with variation to the CDRs and framework regions , as allowed by the claims, would have varying activity as an antibody (page 11915 in col 1 in par 2-4). Other anti- FOLR1 VHH domains and specific binding peptides are also known in the art. For example, U.S. 20190076524 to May et. al. published 14 March 2019 (Of record, IDS dated 7/11/2023) teaches an anti-FOLR1 of SEQ ID NO: 21 which is 73.1% identical to the instant SEQ ID NO: 8 as shown below: ALIGN ALIGNMENT FROM L-NUMBER L1 Query Length: 119; Sequence Length: 113; Score: 172.2 bits (435), 70.0% of highest possible score 246.1; Expect value: 2.869e-41; Identities: 87 / 118 (73.7%); Positives: 95 / 118 (80.5%); Query Identity: 73.1%; Query Coverage: 99.2%; Subject Identity: 77.0%; Subject Coverage: 100.0%; Alignment Length: 118; Q: 2 VQLVESGGGLVQPGGSLRLSCAASESIFSRNHMSWYRQAPGKQRELAAIITSDGNTNYPD 61 ||||||||||||||||||||||| + || + | ||||||||||| |+ || +||| | S: 2 VQLVESGGGLVQPGGSLRLSCAAPGNTFSISAMGWYRQAPGKQREWVAVTHSDYSTNYAD 61 Q: 62 SVKGRFTISRDNAKNTVYLQMNSLKPEDTAVYYCNTFGRSVAGFYDYWGQGTQVTVSS 119 ||||||||||||+|||+|||||||+ |||||||| +| ||||||| ||||| S: 62 SVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCKHYG------IDYWGQGTLVTVSS 113 WO 2019177854 to Wang et. al. published 19 September 2019 teaches an anti-FOLR1 antibody that is 73.1% identical to the instant SEQ ID NO: 8 as shown below: ALIGNMENT FROM L-NUMBER L12 Query Length: 119; Sequence Length: 118; Score: 166.0 bits (419), 67.4% of highest possible score 246.1; Expect value: 7.931e-40; Identities: 87 / 120 (72.5%); Positives: 96 / 120 (80.0%); Query Identity: 73.1%; Query Coverage: 100.0%; Subject Identity: 73.7%; Subject Coverage: 100.0%; Alignment Length: 120; Q: 1 DVQLVESGGGLVQPGGSLRLSCAASESIFSRNHMSWYRQAPGKQRELAAIITSDGN-TNY 59 +|||+|||||||||||||||||| | || ||| |||||| | | |+| |+ | | S: 1 EVQLLESGGGLVQPGGSLRLSCAVSGFTFSNYGMSWVRQAPGKGLEWVATISSGGSYTYY 60 Q: 60 PDSVKGRFTISRDNAKNTVYLQMNSLKPEDTAVYYCNTFGRSVAGFYDYWGQGTQVTVSS 119 ||||||||||||||+|||+|||||||+ ||||||||+| | | |+ |||||| ||||| S: 61 PDSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCSTQGSS--GYVGYWGQGTLVTVSS 118 Neither May et. al. nor Wang et. al. teach the additional functional limitation of not binding to human FOLR2 or FOLR3, so it is unclear whether these antibodies possess that additional functional limitation. A person of ordinary skill in the art would not be able to discern whether these residues are sufficient to meet the recited negative functional limitations without additional experimental evidence. As described by Noel and Rouet , all of the residues of the CDRs and some of the framework regions are required to form the epitope/paratope binding. Regarding antibodies that have the function of binding to FOLR1 but not to FOLR2 and FOLR3, at least one other anti-FOLR1 antibody with these properties is known in the art. U.S. 20140205610 to Ando et. al. (Of record, IDS dated 7/11/2023) teaches anti-huFOLR1 antibody RA15-7 that binds to FOLR1 but not FOLR2 or FOLR3 (Example 19). This antibody comprises a VH/VL and therefore the structural features that result in meeting the functional limitations as claimed are completely distinct from the structural configuration of the instant antibody. For instance, the heavy chain of the RA15-7 SEQ ID NO: 98 is 58.1% identical to instant SEQ ID NO: 8 as shown below: RESULT 1 AASEQ2_04012026_120541 Query Match 58.1%; Score 364.5; DB 1; Length 124; Best Local Similarity 61.4%; Matches 78; Conservative 12; Mismatches 26; Indels 11; Gaps 3; Qy 1 DVQLVESGGGLVQPGGSLRLSCAASESIFSRNHMSWYRQAPGKQRELAAIITSDGN---T 57 :|||||||||||||||||||||||| |: :|:| || ||| | | : | | Db 1 EVQLVESGGGLVQPGGSLRLSCAASGFTFTDFYMNWVRQPPGKAPEWLGFIRNKANGYTT 60 Qy 58 NYPDSVKGRFTISRDNAKNTVYLQMNSLKPEDTAVYYCNTFGRSVAGF-----YDYWGQG 112 : ||||||||||||:||::|||||||| |||| ||| |:: |: | |||| Db 61 EFNPSVKGRFTISRDNSKNSLYLQMNSLKTEDTATYYC---ARTLYGYAYYYVMDAWGQG 117 Qy 113 TQVTVSS 119 | ||||| Db 118 TLVTVSS 124 For the other known anti-FOLR1 antibodies comprising 63% identity over at least 50% of the length of the VHH, it would not be predictable a prior which will not bind to FOLR2 and FOLR3. Regarding derivates of the linker N-succinimidyl-4-guanidinomethyl-3-[I-131]iodobenzoate , the examiner did not find examples of derivatives of N-succinimidyl-4-guanidinomethyl-3-[I-131]iodobenzoate of record. Because derived does not have a universally accepted meaning or standard in the art, the scope of the derivatives of N-succinimidyl-4-guanidinomethyl-3-[I-131]iodobenzoate is expansive because the genus may include derivatives that do not bear structural resemblance to the original. In summary, absent a recitation requiring both the VHH and the fragment to comprise the particular CDRs , it would not be clear to a person of ordinary skill in the art that the inventors were in possession of a genus of all VHHs or fragments thereof with the functional character of binding to FOLR1 but not FOLR2 and FOLR3 and wherein the VHH comprises 63% identity to at least 50% of SEQ ID NO: 8 . Summary of Species disclosed in the original specification The instant specification discloses two families of variable regions based on VHH antibodies A1-A5 comprising SEQ ID NOs: 8, 9, 24, 32, and 40, respectively (Example 1 p. 82 lines 5-24; Table 6 p. 78). Regarding variants of SEQ ID NO: 8 in the variable and binding determinant region , the application discloses SEQ ID NOs: 70-7 3 which are single amino acid variant D59E, N64E, and N64Q. The specification discloses that these three particular mutants did not disrupt the binding function of the parent antibody (Example 8a p. 111). The examiner notes that although SEQ ID NOs: 9, 24, 32, and 40 comprise entirely different CDRs to SEQ ID NO: 8, as shown in the multiple alignment below (CDRs of SEQ ID NO: 8 are bolded) : CLUSTAL O(1.2.4) multiple sequence alignment 32 DVQLVESGGGLARAGGSLRLSCAASGRAFSSTYAMGWFRQAPGKEREFVADINWSEGSPM 60 24 DVQLVESGGGLVQAGGSLRLSCGVSGNMFS-MNLMGWYRQPPGKERDWVAVI-TKDGSTN 58 40 DVQLVESGGGLVQAGGSLRLSCGVSGNIFS-MNLMGWYRQPPGKEREWVALI-TKDGSTN 58 8 DVQLVESGGGLVQPGGSLRLSCAAS ESIFS-RNH MSWYRQAPGKQRELAAI I-TSDGNT N 58 9 DVQLVESGGGLVQAGGSLRLSCAADEMKFS-NYDLAWYRRAPGKQRELAAII-TSGGSTN 58 ***********.: ********... ** :.*:*: ***:*: .* * . *. 32 YIDSVKDRFTISRDNARNSLYLQMNSLKSEDTAVYYCAARRFG----QGYEYWGQGTQVT 116 24 YADSVKGRFTISRDNAKNTVSLQMNSLKPEDTAVYYCNVQDGSGWIRAWGWDWGQGTQVT 118 40 YEDSVKGRFTISRDNAKNTVSLQMNSLKPEDTAVYYCNAQDGSGWIRAWGWDWGQGTQVT 118 8 YPDSVKGRFTISRDNAKNTVYLQMNSLKPEDTAVYYC NTFGRS-VA-GFYDY WGQGTQVT 116 9 YPDSVKGRFTISRDNAKNTVYLEMNSLKPEDTAVYYCNALR-P-WP-QFSDYWGQGTQVT 115 * ****.*********:*:: *:***** ******** . ******** 32 VSS 119 24 VSS 121 40 VSS 121 8 VSS 119 9 VSS 118 *** The specification states that these VHH antibodies are related by binding the same epitopes of FOLR1, but a person of ordinary skill in the art would not be able to determine which how the sequence and structure of the different VHH antibodies are related and how the sequence may be changed in order to preserve the paratope-epitope interaction of the parent antibody as encompassed by the genus of claimed VHHs. Are the disclosed species representative of the claimed genus? MPEP § 2163 states that a “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. The applicant describes 5 single-domain parent antibody clones capable of binding to FOLR1 but not to FOLR2 and FOLR3 within the scope of the instant claims and 4 variants of the elected species SEQ ID NO: 8 . Regarding claim 33, there are no derivatives of N-succinimidyl-4-guanidinomethyl-3-[I-131]iodobenzoate recited in the specification or guidance on how N-succinimidyl-4-guanidinomethyl-3-[I-131]iodobenzoate is to be derivatized (p. 40 lines 19-24). Given the variability encompassed by the genus of compounds comprising a VHH with the recited binding and non-binding functions that comprise 63% identity to SEQ ID NO: 8 or 63% identity over 50% of the length of SEQ ID NO: 8, an artisan would not understand 5 species to be representative of the entire genus. Identifying characteristics and structure/function correlation In the absence of a representative number of species, the written description requirement for a claimed genus may be satisfied by disclosure of relevant, identifying characteristics; i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. To meet this requirement in the instant case, the specification must describe structural features that the skilled artisan as of the effective filing date would have expected to convey the claimed binding activity. The instant specification teaches that the parent antibodies A1-A5 all compete for binding to overlapping epitopes because they each prevent binding of the others. However, this does show possession of a genus of VHH domains comprising the only 63% of SEQ ID NO: 8 or over 50% of SEQ ID NO: 8 because there is no structure/function correlation that would allow an artisan to understand the relationship between the various structures of A1-A5 variable domains and interaction with the epitope. An artisan must individual screen all undisclosed antibodies comprising sequences as instantly claimed in order to determine which fragments of a parent antibody that has only 63% identity over 50% of the length preserve the instantly claimed functions. Summary A genus of species is not present in the instant specification or prior art that would demonstrate a structure/activity relationship would be known for SEQ ID NO: 8 allowing changes by percent identity as claimed . There is a lack of an appropriate number of species with alternative framework structures or polypeptide contexts to demonstrate which VHH framework residues : i ) are essential for binding; ii) can be changed and still allow protein target binding; or iii) disrupt protein target binding. There is a lack of an appropriate number of derivatives or structure/function guidance on how N-succinimidyl-4-guanidinomethyl-3-[I-131]iodobenzoate is to be derivatized. One of skill in the art would reasonably conclude that the applicant was not in possession of the genus of substitutions and deletions of the polypeptide of claim 21 at the time of filing. Regarding claims 22-40 the claims are ultimately dependent on the rejected claim 2 1 without sufficiently narrowing the claimed subject matter and thus are also rejected. Claim Rejections - 35 USC § 112(a) - Scope of Enablement Claims 21-40 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: A compound comprising a VHH or fragment thereof wherein the VHH or fragment thereof compris es the CDRs of SEQ ID NO : 8, or comprising the CDRs of SEQ ID NO: 8 but for the substitutions D59E, N64E, N64Q, and N64S , respectively ; and wherein the VHH or fragment thereof is linked to a radionuclide A method of treating a cancer expressing human FOLR1 on a cancer cell in a subject (claim 37 and 35) comprising administering the compound of (1) or a pharmaceutical composition does not reasonably provide enablement for : A compound comprising any VHH that specifically binds an epitope of human folate receptor alpha (FOLR1), but does not bind human folate receptor beta (FOLR2) or human folate receptor gamma (FOLR3), said VHH being linked to a radionuclide; and wherein said VHH comprises an amino acid sequence having at least 63% sequence identity with at least one of SEQ ID NO: 8, over the full length of said sequence, or over at least 50% of the length of said sequence . A method of treating any cancer associated with an expression of human FOLR1 The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims. There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is "undue." These factors include, but are not limited to: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. Scope of the claimed genus and nature of the invention As described in the written description rejection above, The instant claims are directed towards an antibody or fragment thereof that specifically binds to an epitope of FOLR1 but does not bind to FOLR2 or FOLR3, said VHH being linked to a radionuclide and wherein the VHH comprises an amino acid having at least 63% identity to SEQ ID NO: 8 over the full length of said sequence or over 50% of said sequence . First, the scope is directed towards an antibody or fragment thereof, where both the antibody and the fragment thereof are limited by the functional limitation of specifically binding to FOLR1 but not FOLR2 or FOLR3; however, only the VHH is required to comprise an amino acid sequence having at least 63% identity over 50% or the full length of SEQ ID NO: 8. Regarding fragments, the specification states “Parts, fragments or analogs retaining (at least part of) the functional activity, and/or retaining (at least part of) the binding specificity of the original heavy chain variable domain of an antibody from which these parts, fragments or analogs are derived from are also further referred to herein as ‘functional fragments’ of a heavy chain variable domain” (p. 54 lines 25-29); “For example, the invention provides a number of stretches of amino acid residues (i.e. small peptides), also referred to herein as CDR sequences or part of the antibody fragment as identified as SEQ ID NO, such as sequences having at least 60% identity with at least one of SEQ ID NO: 2, 3, 4,5, 6, 7, 8, 9, 10, 11, 12, 17, 18, 19, 25, 26, 27, 33, 34, 35, 41, 42, 43 of the antibody fragment, preferably VHH’s as disclosed herein” (p. 56 lines 25-29). Therefore, the claims are also directed at smaller fragments of a VHH with 63% identity over 50% of the length of SEQ ID NO: 8, wherein the fragment is does not need to be any particular length, it must only preserve part of the functional limitations of the parent VHH as claimed. Further, the limitations towards 63% identity over 50% of the length of the VHH allows for changes to the binding-determinant CDR regions of the instant VHH antibodies. Claim 22 is directed towards wherein said VHH comprises SEQ ID NO: 8 or SEQ ID NO: 12. However, the claim still does not require that the fragment comprise all of SEQ ID NO: 8 or SEQ ID NO: 12; additionally, comprising SEQ ID NO: 12 is only directed towards the CDR3 and allows for changes to the other binding-determinant CDRs. Claims 23 through 25 define additional functional limitations in regards to the binding affinity of the VHH or fragment thereof to human FOLR1, but they do not specify a particular structure that conveys the claimed binding-affinity function. Claims 26 through 30 are directed towards particular radionuclides but do not limit the structure of the antibody or antibody fragment. Claims 31 through 33 are directed towards particular linkers linked the VHH and the radionuclide but do not limit the structure of the antibody or antibody fragment. Claims 34 through 40 are directed towards pharmaceutical compositions, diagnostic compositions, and methods of treatment comprising the VHH compound or pharmaceutical compositions but do not further limit the structure of the antibody or antibody fragment. Regarding the methods of treatment , the phrase “associated with” does not limit the instant claim to treating cancers that express or overexpress FOLR1 because there is no art-limiting definition of associated with that does not also include those cancers associated with loss of expression. State of the Relevant Art; level of one of ordinary skill; and level of predictability of the art As described in the written description rejection above, It is well established in the art that the formation of an intact antigen-binding site in an antibody usually requires the association of the complete heavy and light chain variable regions of a given antibody, each of which comprises three CDRs (or hypervariable regions) which provide the majority of the contact residues for the binding of the antibody to its target epitope. E.g., Almagro et. al., Front. Immunol. 2018; 8:1751 (see Section “The IgG Molecule” in paragraph 1 and Figure 1). While affinity maturation techniques can result in differences in the CDRs of the antibody compared to its parental antibody (page 3 “The IgG Molecule, second and third paragraphs), those techniques involve trial-and-error testing and the changes that maintain or improve affinity are not predictable a priori . E.g., id. , (page 6 ending paragraph onto page 7). Chiu ML et al. (Antibodies 2019 8, 55, 1-80) taught the antigen binding of antibodies often results in conformational changes in the contact surface areas of both the antibody and the antigen (page 5, first paragraph). Thus, the prediction of CDR binding to the epitope is difficult to predict. Chiu further taught antibody modeling has been shown to be accurate for the framework region sequences, but CDR modeling requires further development and improvements (page 6, second paragraph). Prediction of the structure of HCDR3 could not be accurately produced when given the Fv structures without their CDR-H3s (page 6, second paragraph). Chiu taught the quality of antibody structure prediction, particularly regarding CDR-H3, remains inadequate, and the results of antibody–antigen docking are also disappointing (page 11, paragraph 2) . For a single-domain antibody, the structure of single-domain antibodies and antibody variable domains composed of a single-domain heavy chain (VHH) is known in the art and requires the association of three complete CDRs. As taught by Noël et. al. "Global analysis of VHHs framework regions with a structural alphabet." Biochimie 131 (2016): 11-19 , VHH domains are the variable regions of Heavy Chain Antibodies ( HCAbs ), which are immunoglobulin proteins lacking a light chain and a CH1 domain. Noël et. al. teaches: “ These VHHs are composed of 4 regions whose sequences and structures are defined as conserved (called Framework Regions , FRs ). In addition, VHHs contain three connecting regions showing high variability both in sequence content and structure conformation. These regions are complementary to the antigen surface and are called Complementarity Determining Regions or CDRs). Fig. 1 underlines in 3D (see Fig. 1A [8], [9], [10], [11] , [12] , [13] , [14] , [15] , [16] ) and 2D (see Fig. 1 B) similarities of VHHs to conventional antibodies ” (Introduction, 3 rd para. and Fig. 1). Noël et. al. teaches that the framework regions (FRs) of VHHs are considered to be “constant” regions with a conserved structure, and in some cases a conserved sequence. The FR identity ranged from 76.9% for FR2 to 94.4% for FR4, and the whether there was variation in the amino acids was constrained to particular positions (Fig. 2). In particular, there is a structural pattern that is conserved in the FRs, suggesting that these are not dispensable for antigen-binding function: “ Each of the four FRs is associated to a main structural pattern, which can be considered as canonical, but represents only 40, 84, 63, and 38%, leading to the characterization to variant patterns ranging from 6 to 19. Among some of them, we observe some similarity and the final number of variant patterns could be slightly reduced. However, clearly some are really outliers at more than 1 Å from the main structural pattern and could have strong impact of the proposition of structural models ” (Discussion, 6 th para.). The CDRs of the VHH interact with framework sequences. These interactions would vary between CDR sequences and changes to the framework sequences would change these interactions resulting in changes to the structure and activity of the VHH ( Rouet et. al. Journal of Biological Chemistry. 290(198):11905-11917 (2015) (PTO-892) (Abstract, Figures 5-7). Rouet further teaches that variation in the CDR sequences change the stability of VHH when humanizing a VHH so a consensus framework region of a VHH with variation to the CDRs, as allowed by the claims, would have varying activity as an antibody (page 11915 in col 1 in par 2-4). Regarding the structure of single-domain antibodies, Wagner HJ et al. Int J Mol Sci. 2018 19(11): 3444 teaches in the context of nanobodies, universal scaffolds have been identified, enabling the generation of robust or humanized VHH variants but, this strategy has only been applied to graft CDRs to acceptor frames obtained from animals of the same taxonomic family (page 2, last paragraph). Wagner taught the design of nanobody grafts with CDRs derived from conventional antibodies requires careful consideration, because both the heavy and light chain variable domain (VH and VL) form the antigen binding site and are involved in the recognition of the antigenic epitope (page 2, last paragraph). Furthermore, the framework plays an important role in CDR conformation and orientation and distinct framework residues often contribute directly to antigen binding (page 2, last paragraph). Thus, single-domain antibodies still require defined CDRs. Other anti-FOLR1 VHH domains and specific binding peptides are also known in the art. For example, U.S. 20190076524 to May et. al. published 14 March 2019 (IDS dated 7/11/2023) teaches an anti-FOLR1 of SEQ ID NO: 21 which is 73.1% identical to the instant SEQ ID NO: 8 as shown below: ALIGN ALIGNMENT FROM L-NUMBER L1 Query Length: 119; Sequence Length: 113; Score: 172.2 bits (435), 70.0% of highest possible score 246.1; Expect value: 2.869e-41; Identities: 87 / 118 (73.7%); Positives: 95 / 118 (80.5%); Query Identity: 73.1%; Query Coverage: 99.2%; Subject Identity: 77.0%; Subject Coverage: 100.0%; Alignment Length: 118; Q: 2 VQLVESGGGLVQPGGSLRLSCAASESIFSRNHMSWYRQAPGKQRELAAIITSDGNTNYPD 61 ||||||||||||||||||||||| + || + | ||||||||||| |+ || +||| | S: 2 VQLVESGGGLVQPGGSLRLSCAAPGNTFSISAMGWYRQAPGKQREWVAVTHSDYSTNYAD 61 Q: 62 SVKGRFTISRDNAKNTVYLQMNSLKPEDTAVYYCNTFGRSVAGFYDYWGQGTQVTVSS 119 ||||||||||||+|||+|||||||+ |||||||| +| ||||||| ||||| S: 62 SVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCKHYG------IDYWGQGTLVTVSS 113 WO 2019177854 to Wang et. al. published 19 September 2019 teaches an anti-FOLR1 antibody that is 73.1% identical to the instant SEQ ID NO: 8 as shown below: ALIGNMENT FROM L-NUMBER L12 Query Length: 119; Sequence Length: 118; Score: 166.0 bits (419), 67.4% of highest possible score 246.1; Expect value: 7.931e-40; Identities: 87 / 120 (72.5%); Positives: 96 / 120 (80.0%); Query Identity: 73.1%; Query Coverage: 100.0%; Subject Identity: 73.7%; Subject Coverage: 100.0%; Alignment Length: 120; Q: 1 DVQLVESGGGLVQPGGSLRLSCAASESIFSRNHMSWYRQAPGKQRELAAIITSDGN-TNY 59 +|||+|||||||||||||||||| | || ||| |||||| | | |+| |+ | | S: 1 EVQLLESGGGLVQPGGSLRLSCAVSGFTFSNYGMSWVRQAPGKGLEWVATISSGGSYTYY 60 Q: 60 PDSVKGRFTISRDNAKNTVYLQMNSLKPEDTAVYYCNTFGRSVAGFYDYWGQGTQVTVSS 119 ||||||||||||||+|||+|||||||+ ||||||||+| | | |+ |||||| ||||| S: 61 PDSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCSTQGSS--GYVGYWGQGTLVTVSS 118 Neither May et. al. nor Wang et. al. teach the additional functional limitation of not binding to human FOLR2 or FOLR3, so it is unclear whether these antibodies possess that additional functional limitation. A person of ordinary skill in the art would not be able to discern whether these residues are sufficient to meet the recited negative functional limitations without additional experimental evidence. As described by Noel and Rouet , all of the residues of the CDRs and some of the framework regions are required to form the epitope/paratope binding. Regarding antibodies that have the function of binding to FOLR1 but not to FOLR2 and FOLR3, at least one other anti-FOLR1 antibody with these properties is known in the art. U.S. 20140205610 to Ando et. al. (Of record, cited in IDS dated 7/11/2023) teaches anti-huFOLR1 antibody RA15-7 that binds to FOLR1 but not FOLR2 or FOLR3 (Example 19). This antibody comprises a VH/VL and therefore the structural features that result in meeting the functional limitations as claimed are completely distinct from the structural configuration of the instant antibody. For instance, the heavy chain of the RA15-7 SEQ ID NO: 98 is 58.1% identical to instant SEQ ID NO: 8 as shown below: RESULT 1 AASEQ2_04012026_120541 Query Match 58.1%; Score 364.5; DB 1; Length 124; Best Local Similarity 61.4%; Matches 78; Conservative 12; Mismatches 26; Indels 11; Gaps 3; Qy 1 DVQLVESGGGLVQPGGSLRLSCAASESIFSRNHMSWYRQAPGKQRELAAIITSDGN---T 57 :|||||||||||||||||||||||| |: :|:| || ||| | | : | | Db 1 EVQLVESGGGLVQPGGSLRLSCAASGFTFTDFYMNWVRQPPGKAPEWLGFIRNKANGYTT 60 Qy 58 NYPDSVKGRFTISRDNAKNTVYLQMNSLKPEDTAVYYCNTFGRSVAGF-----YDYWGQG 112 : ||||||||||||:||::|||||||| |||| ||| |:: |: | |||| Db 61 EFNPSVKGRFTISRDNSKNSLYLQMNSLKTEDTATYYC---ARTLYGYAYYYVMDAWGQG 117 Qy 113 TQVTVSS 119 | ||||| Db 118 TLVTVSS 124 For the other known anti-FOLR1 antibodies comprising 63% identity over at least 50% of the length of the VHH, it would not be predictable a prior which will not bind to FOLR2 and FOLR3. In summary, absent a recitation requiring both the VHH and the fragment to comprise the particular CDRs, it would not be clear to a person of ordinary skill in the art that the inventors were in possession of a genus of all VHHs or fragments thereof with the functional character of binding to FOLR1 but not FOLR2 and FOLR3 and wherein the VHH comprises 63% identity to at least 50% of SEQ ID NO: 8. Regarding the treatment of cancers associated with the expression of FOLR1, FOLR1 is generally known to be expressed or overexpressed in cancer. However, as described in the scope of the claims section above, associated with expression of FOLR1 could include cancers associated with loss of FOLR1 expression. For example, Liang Z, et. al. Tandem CAR-T cells targeting FOLR1 and MSLN enhance the antitumor effects in ovarian cancer. Int J Biol Sci. 2021 Oct 22;17(15):4365-4376. doi : 10.7150/ijbs.63181. PMID: 34803504; PMCID: PMC8579462 teaches a method of treating tumors with CAR-T cells targeting both FOLR1 and MSLN (Abstract). FOLR1 and MSLN were highly expressed in most cancers and were higher in late stage cancers (Fig. 2 A-D), however 11.25% of the cancers were found to be both FOLR1 low and MSLN low (Fig. 2). The tandem CAR targeting both antigens performed better in vivo the single antigen CARs (Fig. 6) . Liang et. al. further state that this the tandem CAR design is likely to be improved by preventing antigen escape (Discussion p. 4374) . Thus, a person of ordinary skill in the art would understand that absent a cancer expressing FOLR1, it would take undue experimentation to determine a method of treating a cancer that has reduced or no expression of FOLR1 with a compound comprising an anti-FOLR1 VHH. Amount of direction provided by the inventor; existence of working examples; and quantity of experimentation needed to make or use the invention The instant specification discloses two families of variable regions based on VHH antibodies A1-A5 comprising SEQ ID NOs: 8, 9, 24, 32, and 40, respectively (Example 1 p. 82 lines 5-24; Table 6 p. 78). Regarding variants of SEQ ID NO: 8 in the variable and binding determinant region, the application discloses SEQ ID NOs: 70-72 which are single amino acid variant D59E, N64E, and N64Q. The specification discloses that these three particular mutants did not disrupt the binding function of the parent antibody (Example 8a p. 111). The examiner notes that although SEQ ID NOs: 9, 24, 32, and 40 comprise entirely different CDRs to SEQ ID NO: 8, as shown in the multiple alignment below (CDRs of SEQ ID NO: 8 are bolded): CLUSTAL O(1.2.4) multiple sequence alignment 32 DVQLVESGGGLARAGGSLRLSCAASGRAFSSTYAMGWFRQAPGKEREFVADINWSEGSPM 60 24 DVQLVESGGGLVQAGGSLRLSCGVSGNMFS-MNLMGWYRQPPGKERDWVAVI-TKDGSTN 58 40 DVQLVESGGGLVQAGGSLRLSCGVSGNIFS-MNLMGWYRQPPGKEREWVALI-TKDGSTN 58 8 DVQLVESGGGLVQPGGSLRLSCAAS ESIFS-RNH MSWYRQAPGKQRELAAI I-TSDGNT N 58 9 DVQLVESGGGLVQAGGSLRLSCAADEMKFS-NYDLAWYRRAPGKQRELAAII-TSGGSTN 58 ***********.: ********... ** :.*:*: ***:*: .* * . *. 32 YIDSVKDRFTISRDNARNSLYLQMNSLKSEDTAVYYCAARRFG----QGYEYWGQGTQVT 116 24 YADSVKGRFTISRDNAKNTVSLQMNSLKPEDTAVYYCNVQDGSGWIRAWGWDWGQGTQVT 118 40 YEDSVKGRFTISRDNAKNTVSLQMNSLKPEDTAVYYCNAQDGSGWIRAWGWDWGQGTQVT 118 8 YPDSVKGRFTISRDNAKNTVYLQMNSLKPEDTAVYYC NTFGRS-VA-GFYDY WGQGTQVT 116 9 YPDSVKGRFTISRDNAKNTVYLEMNSLKPEDTAVYYCNALR-P-WP-QFSDYWGQGTQVT 115 * ****.*********:*:: *:***** ******** . ******** 32 VSS 119 24 VSS 121 40 VSS 121 8 VSS 119 9 VSS 118 *** The specification states that these VHH antibodies are related by binding the same epitopes of FOLR1, but a person of ordinary skill in the art would not be able to predict, absent screening the millions of VHH antibodies encompassed by the claims for the recited functional attributes of binding human FOLR1 but not FOLR2 or 3. Regarding methods of treatment, the instant specification uses cancer cells that have expression or high expression of FOLR1 (Specification p. 43 lines 7-12; Example 4b p.88-89). Summary In summary, absent a recitation of the particular CDRs that are binding determinant comprised by the VHH or the fragment thereof, it would take undue experimentation to determine which of the millions of compounds comprising an antibody or fragment thereof meet the functional limitations as claimed . Therefore, the applicant is not enabled for the full scope of claim 2 1. Dependent claims 22-40 are rejected for their dependence on claim 2 1 without resolving the scope of enablement issue as described. The examiner suggests amending the claims such that the VHH or fragment thereof comprises three complete CDR sequences of SEQ ID NO: 8 . Conclusion No claims are allowed. SEQ ID NO: 8 is free of the prior art, but as described in the written description rejection and scope of enablement rejections under 35 U.S.C. 112(a) above, no instant claims require the compound to comprise the entirety of SEQ ID NO: 8 or a complete set of the 3 CDR binding determinant regions thereof . Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT Kathleen CunningChen whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (703)756-1359 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT Monday - Friday 11-8:30 ET . Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. 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If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /KATHLEEN CUNNINGCHEN/ Examiner, Art Unit 1646 /GREGORY S EMCH/ Supervisory Patent Examiner, Art Unit 1678