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 .
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings. Specifically, no sequence identification has been provided for the sequences presented in Figures 3A-3B and 4-5 of the instant specification.
Required response – Applicant must provide:
Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
DETAILED ACTION
Status of Application/Election/Restrictions
3. Applicant’s election of Group I (claims 1-18), SEQ ID NO:11 for CDR1 and SEQ ID NO:18 for ISVD in the reply filed on August 21, 2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
4. Claims 1-21 are pending in this application. Claims 19-21 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable generic or linking claim. Upon reconsideration, the subject matter to the extent of SEQ ID NOs: 12 and 19 are included and under examination in this office action. Election was treated as without traverse in the reply filed on August 21, 2026.
5. Claims 1-18 are under examination with respect to SEQ ID NO:11 or 12 for CDR1 and SEQ ID NO:18 or 19 for ISVD in this office action.
Drawings
6. The drawing/figure 2 is objected to because sequence listings included in the specification must not be duplicated in the drawings. See 37 C.F.R. §1.58(a) and §1.83(a). Appropriate correction is required.
See MPEP § 608.02-I Drawing requirements
If the specification includes a sequence listing or a table, such a sequence listing or table is not permitted to be reprinted in the drawings. 37 CFR 1.83(a) and 1.58(a). If a sequence listing as shown in the drawings has more information than is otherwise contained in the specification, the sequence listing could be included in the specification and the drawings. Applications filed under 35 U.S.C. 371 are excluded from the prohibition from having the same tables and sequence listings in both the description portion of the specification and drawings.
7. The drawings 3A-3B and 4-5 are objected to under 37 CFR 1.83(a). The drawings must show every feature of the invention specified in the claims. Therefore, the sequence identifiers for the sequences shown in figures 3A-3B and 4-5 must be shown or the feature(s) canceled from the claim(s). No new matter should be entered.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
8. The following guidelines illustrate the preferred layout for the specification of a utility application. These guidelines are suggested for the applicant’s use.
Arrangement of the Specification
As provided in 37 CFR 1.77(b), the specification of a utility application should include the following sections in order. Each of the lettered items should appear in upper case, without underlining or bold type, as a section heading. If no text follows the section heading, the phrase “Not Applicable” should follow the section heading:
(a) TITLE OF THE INVENTION.
(b) CROSS-REFERENCE TO RELATED APPLICATIONS.
(c) STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT.
(d) THE NAMES OF THE PARTIES TO A JOINT RESEARCH AGREEMENT.
(e) INCORPORATION-BY-REFERENCE OF MATERIAL SUBMITTED ON A READ-ONLY OPTICAL DISC, AS A TEXT FILE OR AN XML FILE VIA THE PATENT ELECTRONIC SYSTEM.
(f) STATEMENT REGARDING PRIOR DISCLOSURES BY THE INVENTOR OR A JOINT INVENTOR.
(g) BACKGROUND OF THE INVENTION.
(1) Field of the Invention.
(2) Description of Related Art including information disclosed under 37 CFR 1.97 and 1.98.
(h) BRIEF SUMMARY OF THE INVENTION.
(i) BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWING(S).
(j) DETAILED DESCRIPTION OF THE INVENTION.
(k) CLAIM OR CLAIMS (commencing on a separate sheet).
(l) ABSTRACT OF THE DISCLOSURE (commencing on a separate sheet).
(m) SEQUENCE LISTING. (See MPEP § 2422.03 and 37 CFR 1.821 - 1.825). A “Sequence Listing” is required on paper if the application discloses a nucleotide or amino acid sequence as defined in 37 CFR 1.821(a) and if the required “Sequence Listing” is not submitted as an electronic document either on read-only optical disc or as a text file via the patent electronic system.
9. The disclosure is objected to because of the following informalities: The use of the term “ProteOn” (p.7, p. 8) “Nanobody” (p.15; p. 18; p. 20; p. 21), which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks. Appropriate correction is required.
Claim Objections
10. Claims 1-2, 6, 13, 16 and 17 are objected to because of the following informalities:
i. The limitation “Abm” recited in claims 1-2, the limitation “t1/2 beta” recited in claims 6 and 16, and the limitations “(X)n”, “D” and “E1D” recited in claim 17 are not unique or common abbreviations in the art. Applicants are required to spell out “Abm”, “t1/2 beta”, “(X)n”, “D” and “E1D” at the first usage. Appropriate correction is required.
ii. Claim 13 is objected to because the claim recites the limitation “wherein a polypeptide comprises the ISVD”. It should be “wherein the polypeptide comprising the ISVD is administered”. Appropriate correction is required.
11. Claims 19-21 are objected to because of the following informalities: the status of the claims 19-21 is incorrect because these claims are withdrawn from consideration. Appropriate correction is required.
See MPEP 714 & 37 CFR 1.121.
“In the claim listing, the status of every claim must be indicated after its claim number by using one of the following identifiers in a parenthetical expression: (Original), (Currently amended), (Canceled), (Withdrawn), (Previously presented), (New), and (Not entered).”
Claim Rejections - 35 USC § 112
12. 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 1-18 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 pre-AIA the applicant regards as the invention.
Claims 1-18 are indefinite because:
i. Regarding claims 1-2, 6, 16 and 17, the term “Abm” in claims 1-2, the term “t1/2 beta” in claims 6 and 16, and the terms “(X)n”, “D” and “E1D” in claim 17 are recited in the claims without a reference to a precise amino acid sequence identified by a proper structure or providing a full name for abbreviated names. Without identification of property or combination of properties which are unique to and, therefore, definitive of the instant recitations, the metes and bounds of the claims remain undetermined. Further, the use of laboratory designations only to identify a particular molecule renders the claims indefinite because different laboratories may use the same laboratory designations to define completely distinct molecules. For example, based on paragraph [0010] of the specification, the CDRs are defined based on the Kabat definition and the Chothia definition. The rejection based on the limitations “Abm”, “t1/2 beta”, “(X)n”, “D” and “E1D” can be obviated by amending the claims to specifically and uniquely identify “Abm”, “t1/2 beta”, “(X)n”, “D” and “E1D”, for example, by a structure/sequence and function of “Abm”, “t1/2 beta”, “(X)n”, “D” and “E1D”. Thus, the claims are indefinite.
ii. Regarding claim 1, it is unclear whether the limitation “said ISVD” and the limitation “the ISVD” recited in claim 1 refers to the same ISVD. Thus, the claim is indefinite.
iii. Regarding claims 7-9, the limitation “with the sequence of SEQ ID NO: 18 and/or 19 of at least 85%-95%......wherein the CDRs and any C-terminal extension that may be present are not take into account for determining sequence identity or substitutions to SEQ ID NOs: 18/19…” recited in claims 7-9 is unclear. It is unclear as to what Applicant intended to include within the scope of the claim because it is unclear whether the claimed ISVD comprises “any C-terminal extension”.
iv. Regarding claims 10 and 17, the limitation “one or more mutations that reduce the binding by pre-existing antibodies” recited in claims 10 and 17 is unclear. It is unclear what mutations are and what pre-existing antibodies are. The metes and bounds of what is encompassed within the limitation “one or more mutations that reduce the binding by pre-existing antibodies” cannot be determined, which renders the claim indefinite. In addition, the limitation “…….the binding by pre-existing antibodies” in line 7 of the claim. There is insufficient antecedent basis for this limitation in the claim.
v. Regarding claim 13, the limitation “a polypeptide comprises the ISVD” recited in claim 13 is unclear. It is unclear what Applicant intended to claim and include within the claim, which renders the claim indefinite. For examination purposes, the limitation is interpreted as “wherein the polypeptide comprising the ISVD is administered”.
vi. Regarding claim 14, claim 14 recites the limitation “at least one therapeutic moiety or entity”. The limitation “at least one therapeutic moiety or entity” is not necessarily a polypeptide. Thus, the claimed therapeutic moiety or entity” cannot be comprised by the claimed polypeptide of claim 13, which renders the claim indefinite. For examination purposes, claim 14 is interpreted as “a polypeptide according to claim 13, wherein the polypeptide further comprises at least one therapeutic moiety or entity”.
vii. Regarding claim 17, it is unclear whether the limitation “the polypeptide” and the limitation “said polypeptide” refers to the same polypeptide. It is also unclear whether the limitation “said N-/C-terminal ISVD” and the limitation “the ISVD” refers to the same “ISVD”. Thus, the claim is indefinite.
viii. The rest of claims are indefinite as depending from an indefinite claim.
Claim Rejections - 35 USC § 112
13. 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 1-18 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
“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. In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)”. See MPEP § 2164.01.
Claims 1-18 are drawn to a method for preventing or treating a disease or condition in a subject, comprising administering to the subject an ISVD or a polypeptide comprising the ISVD, wherein the ISVD is capable of binding to serum albumin and comprises a CDR1 that is the amino acid sequence of SEQ ID NO:11 or 12, or an amino acid sequence having 2 or 1 amino acid differences with SEQ ID NO:11 or 12; a CDR2 that is the amino acid sequence of SEQ ID NO:13 or an amino acid sequence having 3, 2, or 1 amino acid differences with SEQ ID NO:13; and a CDR3 that is the amino acid sequence of SEQ ID NO:14 or an amino acid sequence having 3, 2 or 1 amino acid differences with SEQ Id NO:14, optionally the serum albumin is human serum albumin.
The claims encompass a method for preventing, treating, and curing all forms of undefined diseases including neurodegenerative diseases of the CNS and all possible inherited genetic disorders using the claimed ISVD or a polypeptide comprising the claimed ISVD, wherein the ISVD comprising CDRs1-3 of SEQ ID NOs:11/12, 13 and 14 respectively or variants thereof in view of paragraphs [0156] of the instant specification (based on published application). The claims also encompass using structurally and functionally undefined variants of ISVD having at least 3, 2, or 1 amino acid differences in recited SEQ ID NOs: for CDRs.
The instant invention is based on characterization of an ISVD comprising the amino acid sequence of SEQ ID NO:19 and its binding affinity to a human serum albumin or serum albumin in other species (see Examples 1-3 and tables 1-2).
Applicant extrapolates the above findings to the claimed method for preventing, treating, and curing all forms of undefined diseases including neurodegenerative diseases of the CNS and all possible inherited genetic disorders using the claimed ISVD or a polypeptide comprising the claimed ISVD, wherein the ISVD comprising CDRs1-3 of SEQ ID NOs:11/12, 13 and 14 respectively or variants thereof.
First, Applicant is not enabled for a method for preventing, treating, and curing all forms of undefined diseases including neurodegenerative diseases of the CNS and all possible inherited genetic disorders using the claimed ISVD or a polypeptide comprising the claimed ISVD, wherein the ISVD comprising CDRs1-3 of SEQ ID NOs:11/12, 13 and 14 respectively or variants thereof.
The instant claims recite the limitation “preventing or treating a disease or condition in a subject", which encompasses preventing and curing all forms of undefined diseases including neurodegenerative diseases of the CNS and all possible inherited genetic disorders in view of definition of “prevention and/or treatment” defined at paragraph [0156] of the published application.
[0156] In the context of the present invention, the term “prevention and/or treatment” not only comprises preventing and/or treating the disease, but also generally comprises preventing the onset of the disease, slowing or reversing the progress of disease, preventing or slowing the onset of one or more symptoms associated with the disease, reducing and/or alleviating one or more symptoms associated with the disease, reducing the severity and/or the duration of the disease and/or of any symptoms associated therewith and/or preventing a further increase in the severity of the disease and/or of any symptoms associated therewith, preventing, reducing or reversing any physiological damage caused by the disease, and generally any pharmacological action that is beneficial to the patient being treated.
However, neither the specification nor the prior art provides any guidance as to how to prevent a person from having an undefined disease including all forms of diseases, all forms of neurodegenerative diseases of the CNS and the PNS, and all forms of inherited genetic disorders caused by all possible mechanisms or how to cure all forms of diseases, all forms of neurodegenerative diseases of the CNS and all forms of inherited genetic disorders caused by all possible mechanisms.
Any individual has a potential to develop any disease including any form of CNS neurodegenerative disease or any inherited genetic disorder caused by all possible mechanisms. Applicant fails to teach how to identify or predict when and which person among us would be susceptible to such a disease or developing the disease and predict when we would need administration of the claimed ISVD or the claimed polypeptide to prevent the disease before the disease occurs.
Neither the specification nor the prior art teaches that administration of the claimed ISVD or the claimed polypeptide or variants thereof can prevent a person from getting any undefined disease including all forms of diseases, all forms of CNS and PNS neurodegenerative diseases and all forms of inherited genetic disorders caused by all possible mechanisms. The cause of the disease can be due to a genetic mutation, which is a natural process. The causes of all forms of diseases, all forms of CNS and PNS neurodegenerative diseases and all forms of inherited genetic disorders caused by all possible mechanisms are different. For example, there are many factors involved in molecular mechanisms contributing to the formation of b-amyloid deposits and neurofibrillary tangles in AD. They include genetic mutations affecting the processing of APP or other molecules involved in protein processing and targeting in view of Henstridge et al. (see p. 94, Henstridge et al., Nat. Rev. Neurosci. 2019; 20: 94-107), Tayebati (see p. 106, 1st col, 2nd paragraph, Tayebati, Mech. Ageing Dev. 2006. 127: 100-8) and Sarter (see p. 645, abstract, Sarter, Neurosci. and Biobehav. Rev. 2004. 28: 645-650). If the cause is due to genetic deficits or mutations, it is impossible to prevent a person from getting or developing AD because a genetic mutation or gene deficiency is a natural process result. The specification fails to provide sufficient guidance as to enable one of skill in the art to practice the invention as it pertains to a method of prevention or curing. Further, Applicant also fails to provide specific guidance as to what specific amount of the claimed ISVD or the claimed polypeptide or variants thereof can be used and thus would be effective to prevent or cure all forms of diseases, all forms of CNS/PNS neurodegenerative diseases and all forms of inherited genetic disorders caused by all possible mechanisms. Thus, a skilled artisan cannot contemplate a right amount to prevent the disease or to prevent a person from getting the disease or to cure the disease.
Second, the specification provides no guidance to enable one of skill in the art to practice the full scope of the claimed invention without undue experimentation because of the complexity and unpredictability of the undefined diseases and the failure to provide support a correlation between the claimed ISVD or polypeptide or variants thereof binding to human serum albumin and the pathogeneses or causes of all forms of diseases including all forms of CNS/PNS neurodegenerative diseases and all forms of inherited genetic disorders caused by all possible mechanisms.
For example, there is no well-established structural and functional relationship or correlation between the claimed ISVD or polypeptide or variants thereof binding to human serum albumin and the pathogeneses or causes CNS neurodegenerative diseases including all forms of AD in vivo in view of Falkenburger et al. (see p.261, summary; Falkenburger et al., J. Neural. Transm, 2006; 70:261-268), Tayebati (see p. 106, 1st col, 2nd paragraph, Tayebati, Mech. Ageing Dev. 2006. 127: 100-8) and Sarter (see p. 645, abstract, Sarter, Neurosci. and Biobehav. Rev. 2004. 28: 645-650).
While the skill level in the art is high, the level of predictability is low. For example, the molecular mechanisms underlying cognitive dysfunction or dementia of AD are unclear (see p. 94; Henstridge et al. Nat. Rev. Neurosci. 2019; 20: 94-107). The specification provides insufficient guidance to demonstrate that administration of the claimed ISVD or polypeptide or variants thereof can treat cognitive dysfunction or dementia in AD because there is no well-established relationship or correlation between serum albumin/binding to serum albumin and pathogenesis of AD. Several factors and genes are involved in pathogenesis of AD including ageing, inflammation and immune response, APP, presenilin1/2, ApoE and genes involved in the amyloid cascade, genes involved in the mitochondrial cascade as taught by Swerdlow (p. 348-344, Swerdlow, Clin. Interv. Ageing 2007; 2:347-359), Atwood et al. (p.33, abstract; Atwood et al., J. Alzheimer’s Disease; 2015; 47:33-47) and Henstridge et al. (p. 95-103; Henstridge et al., Nat. Rev. Neurosci. 2019; 20: 94-107). However, these factors are not related to serum albumin or binding to human serum albumin. The specification provides no support such as an animal model of the disease related to binding to human serum albumin, or for example, an animal model of AD and tests closely reflect AD, including 1) tests currently used to identify in rodents deficits associated with AD; 2) tests to identify Alzheimer-related signs in patients; and 3) tests that relate to theoretical constructs of human and animal cognition, which should include at least spatial learning and memory (such as Morris Water Maze and Radial Arm Maze), delayed recall match-to-sample, serial response learning, and visual discrimination (such as vertical vs. horizontal stimuli).(see p. 403, abstract. Anger. Neurotoxicology 1991. 12: 403-13).
Applicant obviously intended to treat all forms of diseases, all forms of CNS/PNS neurodegenerative diseases and all forms of inherited genetic disorders caused by all possible mechanisms by using the claimed ISVD, polypeptides or variants thereof. However, the specification provides no well-established correlation among an ISVD or polypeptides or variants thereof binding to human serum albumin and different forms of diseases including all forms of diseases, all forms of CNS/PNS neurodegenerative diseases and all forms of inherited genetic disorders caused by all possible mechanisms. The specification also fails to establish that different forms of diseases including all forms of diseases, all forms of CNS/PNS neurodegenerative diseases and all forms of inherited genetic disorders caused by different mechanisms or all possible mechanisms can be treated by the same drugs or same conditions or have the same effects in response to the same drugs. Thus, it is unpredictable whether administration of the claimed ISVD, polypeptides or variants thereof can treat any disease including all forms of diseases, all forms of CNS/PNS neurodegenerative diseases and all forms of inherited genetic disorders caused by all possible mechanisms. It is also unpredictable whether one treatment for one specific disorder can be applied to another disorder, indicating undue experimentation is required by a skilled artisan to perform while practice the claimed invention.
Further, the specification fails to provide sufficient guidance as to what other variant ISVDs or polypeptides or variants thereof are and whether all variant ISVDs or polypeptides or variants thereof can be used in the claimed method because a single amino acid change on a molecule can abolish the binding ability of a molecule. For example, a substitution of lysine residue by glutamic acid at position 118 of acidic fibroblast growth factor results in a substantial loss of its biological activity including the binding ability to heparin and its receptor (Burgess et al. J of Cell Bio. 1990, 111:2129-2138). Even if an active or binding site were identified in the specification, they may not be sufficient, as the ordinary artisan would not immediately recognize that an active or binding site must assume the proper three-dimensional configuration to be active because conformation is dependent upon surrounding residues; i.e. substitution of non-essential residues can often destroy activity. In addition to a core determinant sequence, the protein-protein interaction also relies on the flanking or noncontiguous residues (see p. 445 the second column, first paragraph, Pawson et al. 2003, Science 300:445-452). The optimal binding motif for a domain is not necessarily suitable for physiological or in vivo interaction. The predictive data always need to be validated by actual analyses in cells (see p. 445, the third column, second paragraph, Pawson et al. 2003, Science 300:445-452). Alaoui-lsmaili teaches that designing a mutein having predictable activities is difficult because of the complexity of the interactions between ligands and receptors (Alaoui-lsmaili et al., Cytokine Growth Factor Rev. 2009; 20:501-507). For example, given the complexity of BMP-BMP receptor interactions, it is difficult to design BMPs with improved affinity and/or specificity for one specific receptor. More importantly, predicting the in vivo biological activity of such altered BMPs remains a challenging undertaking (see p. 502, right col., 2th paragraph). Further, when multiple mutations are introduced, there is even less predictability because Guo et al. teaches that the effects of mutations on protein function are largely additive (see p. 9207, left col., 2th paragraph, Guo et al., PNAS 2004; 101:9205-9210). The specification fails to teach what other structures/amino acid sequences can or cannot not be included/changed in all variant ISVDs or polypeptides or variants thereof for preventing or treating all forms of diseases, all forms of CNS/PNS neurodegenerative diseases and all forms of inherited genetic disorders caused by all possible mechanisms, indicating undue experimentation is required by a skilled artisan to perform while practicing the claimed invention.
A patent is granted for a completed invention, not the general suggestion of an idea and how that idea might be developed into the claimed invention. In the decision of Genentec, Inc, v. Novo Nordisk, 42 USPQ 2d 100,(CAFC 1997), the court held that:
“[p]atent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable” and that “[t]ossing out the mere germ of an idea does not constitute enabling disclosure”. The court further stated that “when there is no disclosure of any specific starting material or of any of the conditions under which a process is to be carried out, undue experimentation is required; there is a failure to meet the enablement requirements that cannot be rectified by asserting that all the disclosure related to the process is within the skill of the art”, “[i]t is the specification, not the knowledge of one skilled in the art, that must supply the novel aspects of an invention in order to constitute adequate enablement”.
The instant specification is not enabling because one cannot follow the guidance presented therein and practice the claimed method without first making a substantial inventive contribution.
Therefore, in view of the breadth of the claims, the lack of guidance in the specification, the lack of working examples, the unpredictability of inventions, and the current status of the art, undue experimentation would be required by one of skill in the art to perform in order to practice the full scope of the claimed invention as it pertains to a method for preventing or treating a disease in a subject by the claimed ISVD, polypeptides or variants thereof.
Claim Rejections - 35 USC § 112
14. Claims 1-18 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof.
Claims 1-18 encompass preventing or treating a genus of undefined diseases using a genus of ISVD, polypeptides or variants thereof capable of binding to serum albumin/human serum albumin, wherein the ISVD comprises SEQ ID NOs: 11/12-14 for the CDRs1-3 and variants within the recited CDRs1-3 of SEQ ID NOs:11/12-14. Claim 4 encompasses using a genus of heavy-chain ISVD. Claim 5 encompasses using a genus of VHH, humanized VHH, camelized VH and a camelized VH. Claim 6 encompasses using a genus of ISVD or polypeptide having a half-life of more than 6, 12, 24, or 72hrs in human serum. Claims 7-8 encompass using a genus of variants of SEQ ID NO: 18 or 19 with at least 85%-95% sequence identity to SEQ ID NO: 18 or 19. Claim 10 encompasses using a genus of ISVD comprising one or more mutations that reduce the binding of structurally and functionally undefined pre-existing antibodies. Claims 13-18 encompass a genus of polypeptides and a therapeutic moiety or entity having a half-life of more than 6, 12, 24, or 72hrs in human serum. Claim 17 encompasses using a genus of polypeptide comprising C-terminal/N-terminal ISVD and one or more mutations that reduce the binding of structurally and functionally undefined pre-existing antibodies.
In making a determination of whether the application complies with the written description requirement of 35 U.S.C. 112, first paragraph, it is necessary to understand what Applicant is in possession of and what Applicant is claiming.
M.P.E.P. § 2163 instructs:
An invention described solely in terms of a method of making and/or its function may lack written descriptive support where there is no described or art-recognized correlation between the disclosed function and the structure(s) responsible for the function. . . .
An applicant may show possession of an invention by disclosure of drawings or structural chemical formulas that are sufficiently detailed to show that applicant was in possession of the claimed invention as a whole. . . .
An applicant may also show that an invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics which provide evidence that applicant was in possession of the claimed invention, i.e., complete or partial structure, other physical and/or chemical properties, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics.”
This standard has not been met in this case. The specification only showed characterization of an ISVD comprising the amino acid sequence of SEQ ID NO:19 and its binding affinity to a human serum albumin or serum albumin in other species (see Examples 1-3 and tables 1-2).
However, Applicant is not in possession of the claimed method for preventing or treating a genus of undefined disease using the claimed genus of ISVD, variant ISVD, polypeptides or variants thereof. The specification provides no identification of any particular portion of the structure that must be conserved for the claimed genus of ISVD, variant ISVD, polypeptides or variants thereof that can be used for preventing or treating a genus of undefined diseases. The instant specification fails to provide sufficient descriptive information, such as definitive structural or functional features of the claimed genus of ISVD, variant ISVD, polypeptides or variants thereof. There is no description of the conserved regions which are critical to the function of the genus claimed. There is no description of the sites at which variability may be tolerated and there is no information regarding the relation of the structure of other ISVD, variant ISVD, polypeptides or variants thereof to the function of SEQ ID NO:19 or 18 in binding human serum albumin. The specification also provides no well-established structural and functional relationship or correlation between SEQ ID NO:19 or 18 binding to human serum albumin and prevention or treatment of a genus of undefined diseases. Furthermore, the prior art does not provide compensatory structural or correlative teachings sufficient to enable one of skill to identify what other ISVD, variant ISVD, polypeptides or variants thereof might be and whether they can be used for prevention or treatment of all forms of undefined diseases including all forms of diseases, all forms of CNS/PNS neurodegenerative diseases and all forms of inherited genetic disorders caused by all possible mechanisms.
Since the common characteristics/features of other ISVD, variant ISVD, polypeptides or variants thereof are unknown and their effects and use for prevention or treatment of all forms of undefined diseases including all forms of diseases, all forms of CNS/PNS neurodegenerative diseases and all forms of inherited genetic disorders caused by all possible mechanisms are also unknown, a skilled artisan cannot contemplate the functional correlations of the genus with the claimed invention. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of using the genus of ISVD, variant ISVD, polypeptides or variants thereof for prevention or treatment of the genus of undefined diseases including all forms of diseases, all forms of CNS/PNS neurodegenerative diseases and all forms of inherited genetic disorders caused by all possible mechanisms.
As stated in M.P.E.P. § 2163(II)(A)(3), a specification may describe an actual reduction to practice by showing that the inventor constructed an embodiment or performed a process that met all the limitations of the claim and determined that the invention would work for its intended purpose. Cooper v. Goldfarb, 154 F.3d 1321,1327, 47 USPQ2d 1896, 1901 (Fed. Cir. 1998). See also UMC Elecs. Co. v. United States, 816 F.2d 647, 652, 2 USPQ2d 1465, 1468 (Fed. Cir. 1987) (“[T]here cannot be a reduction to practice of the invention ... without a physical embodiment which includes all limitations of the claim.”); Estee Lauder Inc. v. L’Oreal, S.A., 129 F.3d 588, 593, 44 USPQ2d 1610, 1614 (Fed. Cir. 1997) (“[A] reduction to practice does not occur until the inventor has determined that the invention will work for its intended purpose.”); Mahurkar v. C.R. Bard, Inc., 79 F.3d 1572, 1578, 38 USPQ2d 1288, 1291 (Fed. Cir. 1996) (determining that the invention will work for its intended purpose may require testing depending on the character of the invention and the problem it solves).
Whereas a reduction to practice of an uncomplicated invention such as a simple mechanical or electrical device can be achieved by merely providing a diagram of the device wherein one skilled in the relevant art can predict the likely operability of the device by reviewing the diagram, the operability of the claimed invention cannot be predicted by merely reviewing diagrams or illustrations.
To demonstrate the reduction to practice of an ISVD, variant ISVD, polypeptides or variants thereof and a method of treating an animal by the administration of that ISVD, variant ISVD, polypeptides or variants thereof requires either a working embodiment, a demonstration of operability in the treatment of an art accepted animal model of the condition to be treated wherein that animal model has been shown to be reliably predictive of efficacy in the treatment of the condition, or a demonstration that the therapeutic agent employed therein possesses an activity in which the majority of compounds possessing that activity have been shown to be effective in the treatment of that condition. In the instant case, Applicant has provided none of these. Consequently, Applicant has failed to demonstrate possession of the claimed method or even using a single species of the genus of ISVD, variant ISVD, polypeptides or variants thereof required thereby as of the earliest effective filing date of the instant application.
With respect to the demonstration of a reduction to practice of a generic invention, M.P.E.P. § 2163(II)(A)(3)(ii) states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or 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, above). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. 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. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014).
The above position is further supported by In re Clarke, 148 USPQ 665, (CCPA 1966), which held that; “It appears to be well settled that a single species can rarely, if ever, afford support fora generic claim. In re Soil, 25 C.C.P.A. (Patents) 1309, 97 F.2d 623, 38 USPQ 189; In re Wahlforss et al., 28 C.C.P.A. (Patents) 867,117 F.21 270,48 USPQ 397. The decisions do not however fix any definite number of species which will establish completion of a generic invention and it seems evident therefrom that such number will vary, depending on the circumstances of particular cases. Thus, in the case of a small genus such as halog ens, consisting of four species, a reduction to practice of three, or perhaps even two, might serve to complete the generic invention, while in the case of a genus comprising hundreds of species, a considerably large number of reductions to practice would probably be necessary.”
In the instant case, Applicant has failed to demonstrate a reduction to practice of using a representative number species of the genus of “ISVD, variant ISVD, polypeptides or variants thereof” for treatment of a defined disease, or even a single species within that genus for treatment of a species of the genus of defined disease, much less a method for preventing or treating a subject afflicted with a undefined disease by the administration of such ISVD, variant ISVD, polypeptides or variants thereof thereto. The experimental results described in the specification consist primarily of the characterization of an ISVD of SEQ ID NO:19 and its binding affinity to serum albumin in different species. The data of the ISVD of SEQ ID NO:19 binding to human serum albumin do not support a conclusion that Applicant was in possession of a method for preventing or treating a disease or condition in a subject by the administration thereto of the claimed genus of “ISVD, variant ISVD, polypeptides or variants thereof” because there is no well-established structural and functional relationship or correlation between an ISVD or polypeptide or variant thereof binding to human serum albumin and prevention/treatment of a genus of undefined diseases. Thus, those results do not constitute a reduction to practice a method for preventing or treating a genus of undefined diseases or conditions in a subject using the claimed genus of ISVD or polypeptide or variant thereof binding to human serum albumin and prevention/treatment of a genus of undefined diseases.
Based on MPEP § 2161.01 and §2163, “to satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116”.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116).
As discussed above, the skilled artisan cannot envision the detailed chemical structure of the encompassed genus of ISVD or polypeptide or variant thereof binding to human serum albumin and prevention/treatment of a genus of undefined diseases, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483.
Therefore, the claimed method for preventing or treating a disease or condition using the claimed ISVD or polypeptide or variant thereof binding to serum albumin/human serum albumin has not met the written description provision of 35 U.S.C. §112, first paragraph. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (see page 1115). Applicant is directed to the Guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, ¶ 1 "Written Description" Requirement. See MPEP § 2161.01 and 2163.
Conclusion
15. NO CLAIM IS ALLOWED.
Sequence alignment
SEQ ID NO:18 1 EVQLVESGGGLVQAGGSLRLSCAASGSNISSYVMGWFRRAPGKEREFVAAISRSGGYTYY 60
SEQ ID NO:19 1 EVQLVESGGGVVQPGGSLRLSCAASGSTISSYVMGWFRRAPGKEREFVAAISRSGGYTYY 60
SEQ ID NO:20 1 EVQLVESGGGVVQPGGSLRLSCAASGSNISSYVMGWFRRAPGKEREFVAAISRSGGYTYY 60
SEQ ID NO:1 1 EVQLVESGGGLVQPGNSLRLSCAASGFTFSSFGMSWVRQAPGKGLEWVSSISGSGSDTLY
SEQ ID NO:2 1 EVQLLESGGGLVQPGGSLRLSCAASGFTFRSFGMSWVRQAPGKGPEWVSSISGSGSDTLY
SEQ ID NO:11 1 -------------------------GSNISSYVMG------------------------- 10
SEQ ID NO:12 1 -------------------------GSTISSYVMG------------------------- 10
SEQ ID NO:13 1 -------------------------------------------------AISRSGGYTY- 10
SEQ ID NO:14 1 ------------------------------------------------------------
SEQ ID NO:9 1 ------------------------------SYVMG------------------------- 5
SEQ ID NO:10 1 -------------------------------------------------AISRSGGYTYY 11
SEQ ID NO:68 1 DVQLVESGGGVVQPGGSLRLSCAASGRTFSSYAMGWFRQAPGKEREFVAAISWSDGSTYY 60
SEQ ID NO:18 61 ADSVKGRFTISRDNAKKTAYLQMNSLEPEDTAVYYCAAGRYSAWYSQSYEYDYWGQGTLV 120
SEQ ID NO:19 61 ADSVKGRFTISRDNSKKTAYLQMNSLRPEDTALYYCAAGRYSAWYSQSYEYDYWGQGTLV 120
SEQ ID NO:20 61 ADSVKGRFTISRDNSKKTAYLQMNSLRPEDTALYYCAAGRYSAWYSQSYEYDYWGQGTLV 120
SEQ ID NO:1 61 ADSVKGRFTISRDNAKTTLYLQMNSLRPEDTAVYYCTIGGSLSRSSQGTLVTVSS----- 115
SEQ ID NO:2 61 ADSVKGRFTISRDNSKNTLYLQMNSLRPEDTAVYYCTIGGSLSRSSQGTLVTVSS----- 115
SEQ ID NO:11 ------------------------------------------------------------
SEQ ID NO:12 ------------------------------------------------------------
SEQ ID NO:13 ------------------------------------------------------------
SEQ ID NO:14 --------------------------------------GRYSAWYSQSYEYDY------- 15
SEQ ID NO:10 12 ADSVKG------------------------------------------------------ 17
SEQ ID NO:68 61 ADSVKGRFTISRDNAKNTVYLQMNSLRPEDTALYYCAADLTSTNPGSYIYIWAYDYWGQG 120
SEQ ID NO:18 121 TVSS 124
SEQ ID NO:19 121 TVSS 124
SEQ ID NO:20 121 TVSS 124
SEQ ID NO:1 ----
SEQ ID NO:2 ----
SEQ ID NO:11 ----
SEQ ID NO:12 ----
SEQ ID NO:13 ----
SEQ ID NO:14 ----
SEQ ID NO:10 ----
SEQ ID NO:68 121 TLVTVSSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSEVQLVESGGGVVQPGGSL 180
SEQ ID NO:68 181 RLSCAASGRTFSSYAMGWFRQAPGKEREFVAAISWSDGSTYYADSVKGRFTISRDNAKNT 240
SEQ ID NO:68 241 VYLQMNSLRPEDTALYYCAADLTSTNPGSYIYIWAYDYWGQGTLVTVSSGGGGSGGGGSG 300
SEQ ID NO:68 301 GGGSGGGGSGGGGSGGGGSGGGGSEVQLVESGGGVVQPGGSLRLSCAASGSTISSYVMGW 360
SEQ ID NO:68 361 FRRAPGKEREFVAAISRSGGYTYYADSVKGRFTISRDNSKKTAYLQMNSLRPEDTALYYC 420
SEQ ID NO:68 421 AAGRYSAWYSQSYEYDYWGQGTLVTVSS-------------------------------- 448
SEQ ID NO:11=10aa
SEQ ID NO:12=10aa
SEQ ID NO:13=10aa
SEQ ID NO:14=15aa
SEQ ID NOs: 11/12-14=35aa
SEQ ID NO:18=124aa
SEQ ID NO:19=124aa
16. The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Stijlemans (WO2014037419, as in IDS) teaches an immunoglobulin single variable domain nanobody CA4435 binding to serum albumin, comprising the amino acid sequence of SEQ:23, which is 85.5% identical to instant SEQ ID NO:18 or 82.6% identical to instant SEQ ID NO:19 (see the sequence alignment below; p. 20-28, examples 1-4, claims 1-14, in particular).
SEQ ID NO:18
BBD48369
ID BBD48369 standard; protein; 258 AA.
XX
AC BBD48369;
XX
DT 24-APR-2014 (first entry)
XX
DE Immunoglobulin single variable domain nanobody CA4435, SEQ:23.
XX
KW antiinflammatory; breast tumor; burkitts lymphoma; cancer; colon tumor;
KW colorectal tumor; cytostatic; diagnostic test; glioblastoma;
KW head and neck tumor; immunoglobulin; inflammatory disease; leukemia;
KW lymphoma; metastatic non small cell lung cancer; ovary tumor;
KW prophylactic to disease; prostate tumor; protein detection;
KW small-cell lung cancer; stomach tumor; therapeutic; uterine cervix tumor.
XX
OS Unidentified.
XX
CC PN WO2014037419-A1.
XX
CC PD 13-MAR-2014.
XX
CC PF 04-SEP-2013; 2013WO-EP068315.
XX
PR 04-SEP-2012; 2012US-0696644P.
XX
CC PA (VIBV-) VIB VZW.
CC PA (ULBR ) UNIV VRIJE BRUSSEL.
XX
CC PI Stijlemans B, De Baetselier P;
XX
DR WPI; 2014-E48967/21.
XX
CC PT New immunoglobulin single variable domain that is directed against and/or
CC PT that specifically binds to human and/or mouse cluster of differentiation-
CC PT 74, useful for preventing or treating inflammatory disease or cancer, and
CC PT detecting protein.
XX
CC PS Disclosure; SEQ ID NO 23; 76pp; English.
XX
CC The present invention relates to an immunoglobulin single variable domain
CC that is directed against and/or that specifically binds to human and/or
CC mouse cluster of differentiation-74 (CD74). The immunoglobulin single
CC variable domains and compositions of the invention can be used for
CC therapeutic, prophylactic or diagnostic purposes. The immunoglobulin
CC single variable domain is useful for: preventing and/or treating an
CC inflammatory disease; detecting a protein; and treating cancer comprising
CC breast cancer, ovarian cancer, cervical cancer, glioblastoma, leukemia,
CC lymphoma, prostate cancer, Burkitt's lymphoma, head and neck cancer,
CC colon cancer, colorectal cancer, non-small cell lung cancer, small cell
CC lung cancer or gastric cancer. The present sequence represents an
CC immunoglobulin single variable domain nanobody CA4435 used for preventing
CC and/or treating an inflammatory disease.
XX
SQ Sequence 258 AA;
Query Match 85.5%; Score 555; DB 21; Length 258;
Best Local Similarity 85.5%;
Matches 106; Conservative 5; Mismatches 13; Indels 0; Gaps 0;
Qy 1 EVQLVESGGGLVQAGGSLRLSCAASGSNISSYVMGWFRRAPGKEREFVAAISRSGGYTYY 60
:||| ||||||||||||||||||||| ||| |||||||:||||||||||||| | | ||
Db 135 QVQLQESGGGLVQAGGSLRLSCAASGRNISEYVMGWFRQAPGKEREFVAAISWSAGNIYY 194
Qy 61 ADSVKGRFTISRDNAKKTAYLQMNSLEPEDTAVYYCAAGRYSAWYSQSYEYDYWGQGTLV 120
|||||||||||||||| | :||||:| |||||||||||||||||| :|||||||||| |
Db 195 ADSVKGRFTISRDNAKNTVHLQMNTLRPEDTAVYYCAAGRYSAWYVAAYEYDYWGQGTQV 254
Qy 121 TVSS 124
||||
Db 255 TVSS 258
SEQ ID NO:19
BBD48370
ID BBD48370 standard; protein; 258 AA.
XX
AC BBD48370;
XX
DT 24-APR-2014 (first entry)
XX
DE Immunoglobulin single variable domain nanobody CA4435, SEQ:24.
XX
KW antiinflammatory; breast tumor; burkitts lymphoma; cancer; colon tumor;
KW colorectal tumor; cytostatic; diagnostic test; glioblastoma;
KW head and neck tumor; immunoglobulin; inflammatory disease; leukemia;
KW lymphoma; metastatic non small cell lung cancer; ovary tumor;
KW prophylactic to disease; prostate tumor; protein detection;
KW small-cell lung cancer; stomach tumor; therapeutic; uterine cervix tumor.
XX
OS Unidentified.
XX
CC PN WO2014037419-A1.
XX
CC PD 13-MAR-2014.
XX
CC PF 04-SEP-2013; 2013WO-EP068315.
XX
PR 04-SEP-2012; 2012US-0696644P.
XX
CC PA (VIBV-) VIB VZW.
CC PA (ULBR ) UNIV VRIJE BRUSSEL.
XX
CC PI Stijlemans B, De Baetselier P;
XX
DR WPI; 2014-E48967/21.
XX
CC PT New immunoglobulin single variable domain that is directed against and/or
CC PT that specifically binds to human and/or mouse cluster of differentiation-
CC PT 74, useful for preventing or treating inflammatory disease or cancer, and
CC PT detecting protein.
XX
CC PS Disclosure; SEQ ID NO 24; 76pp; English.
XX
CC The present invention relates to an immunoglobulin single variable domain
CC that is directed against and/or that specifically binds to human and/or
CC mouse cluster of differentiation-74 (CD74). The immunoglobulin single
CC variable domains and compositions of the invention can be used for
CC therapeutic, prophylactic or diagnostic purposes. The immunoglobulin
CC single variable domain is useful for: preventing and/or treating an
CC inflammatory disease; detecting a protein; and treating cancer comprising
CC breast cancer, ovarian cancer, cervical cancer, glioblastoma, leukemia,
CC lymphoma, prostate cancer, Burkitt's lymphoma, head and neck cancer,
CC colon cancer, colorectal cancer, non-small cell lung cancer, small cell
CC lung cancer or gastric cancer. The present sequence represents an
CC immunoglobulin single variable domain nanobody CA4435 used for preventing
CC and/or treating an inflammatory disease.
XX
SQ Sequence 258 AA;
Query Match 82.6%; Score 538; DB 21; Length 258;
Best Local Similarity 82.3%;
Matches 102; Conservative 8; Mismatches 14; Indels 0; Gaps 0;
Qy 1 EVQLVESGGGVVQPGGSLRLSCAASGSTISSYVMGWFRRAPGKEREFVAAISRSGGYTYY 60
:||| |||||:|| |||||||||||| || |||||||:||||||||||||| | |||
Db 135 QVQLQESGGGLVQAGGSLRLSCAASGRNISEYVMGWFRQAPGKEREFVAAISWSSHNTYY 194
Qy 61 ADSVKGRFTISRDNSKKTAYLQMNSLRPEDTALYYCAAGRYSAWYSQSYEYDYWGQGTLV 120
||||||||||||||:| | :||||:|||||||:|||||||||||| :|||||||||| |
Db 195 ADSVKGRFTISRDNAKNTVHLQMNTLRPEDTAVYYCAAGRYSAWYVAAYEYDYWGQGTQV 254
Qy 121 TVSS 124
||||
Db 255 TVSS 258
WO2018134234 (PCT/EP2018/051082 of the parent case) teaches an immunoglobulin single variable domain nanobody CA4435 binding to serum albumin, comprising the amino acid sequence of SEQ:23, which is 85.5% identical to instant SEQ ID NO:18 (see the sequence alignment below; p. 20-28, examples 1-4, claims 1-14, in particular).
SEQ ID NO:18
BFM52835
ID BFM52835 standard; protein; 124 AA.
XX
AC BFM52835;
XX
DT 06-SEP-2018 (first entry)
XX
DE Anti-T0235005G01 nanobody protein SEQ: 18.
XX
KW heavy chain variable region; humanized antibody; nanobody;
KW protein binding; single domain antibody.
XX
OS Synthetic.
OS Unidentified.
XX
CC PN WO2018134234-A1.
XX
CC PD 26-JUL-2018.
XX
CC PF 17-JAN-2018; 2018WO-EP051082.
XX
PR 17-JAN-2017; 2017US-0446992P.
XX
CC PA (ABLY ) ABLYNX NV.
XX
CC PI Staelens S, Steffensen S, Morizzo E, Cerdobbel A;
XX
DR WPI; 2018-582884/53.
XX
CC PT Amino acid sequence is an immunoglobulin single variable domain, where
CC PT immunoglobulin single variable domain is capable of binding to human
CC PT serum albumin that has a complementarity determining region 1, which
CC PT comprises ten amino acid.
XX
CC PS Claim 7; SEQ ID NO 18; 60pp; English.
XX
CC The invention relates to a novel amino acid sequence which is an
CC immunoglobulin single variable domain (ISVD), and in particular heavy-
CC chain immunoglobulin single variable domain, used to bind to serum
CC albumin. The invention claims a pharmaceutical composition, which
CC comprises a protein, polypeptide or other construct, compound, molecule
CC or chemical entity. The present sequence represents a humanized anti-
CC T0235005G01 nanobody protein, used to bind to serum albumin. Note: The
CC present sequence is used as a parent sequence for generating variants
CC (BFM52836-BFM52876).
XX
SQ Sequence 124 AA;
Query Match 100.0%; Score 649; DB 26; Length 124;
Best Local Similarity 100.0%;
Matches 124; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EVQLVESGGGLVQAGGSLRLSCAASGSNISSYVMGWFRRAPGKEREFVAAISRSGGYTYY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVQLVESGGGLVQAGGSLRLSCAASGSNISSYVMGWFRRAPGKEREFVAAISRSGGYTYY 60
Qy 61 ADSVKGRFTISRDNAKKTAYLQMNSLEPEDTAVYYCAAGRYSAWYSQSYEYDYWGQGTLV 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ADSVKGRFTISRDNAKKTAYLQMNSLEPEDTAVYYCAAGRYSAWYSQSYEYDYWGQGTLV 120
Qy 121 TVSS 124
||||
Db 121 TVSS 124
SEQ ID NO:19
BFM52836
ID BFM52836 standard; protein; 124 AA.
XX
AC BFM52836;
XX
DT 06-SEP-2018 (first entry)
XX
DE Humanized anti-T023500043 nanobody mutant protein SEQ: 19.
XX
KW heavy chain variable region; humanized antibody; mutein; nanobody;
KW protein binding; single domain antibody.
XX
OS Synthetic.
OS Unidentified.
XX
CC PN WO2018134234-A1.
XX
CC PD 26-JUL-2018.
XX
CC PF 17-JAN-2018; 2018WO-EP051082.
XX
PR 17-JAN-2017; 2017US-0446992P.
XX
CC PA (ABLY ) ABLYNX NV.
XX
CC PI Staelens S, Steffensen S, Morizzo E, Cerdobbel A;
XX
DR WPI; 2018-582884/53.
XX
CC PT Amino acid sequence is an immunoglobulin single variable domain, where
CC PT immunoglobulin single variable domain is capable of binding to human
CC PT serum albumin that has a complementarity determining region 1, which
CC PT comprises ten amino acid.
XX
CC PS Claim 7; SEQ ID NO 19; 60pp; English.
XX
CC The invention relates to a novel amino acid sequence which is an
CC immunoglobulin single variable domain (ISVD), and in particular heavy-
CC chain immunoglobulin single variable domain, used to bind to serum
CC albumin. The invention claims a pharmaceutical composition, which
CC comprises a protein, polypeptide or other construct, compound, molecule
CC or chemical entity. The present sequence represents a humanized anti-
CC T023500043 nanobody mutant protein L11V/A14P/N28T/A75S/E87R/Y93L, used to
CC bind to serum albumin. Note: The present sequence is derived from a
CC parent sequence BFM52835.
XX
SQ Sequence 124 AA;
Query Match 100.0%; Score 651; DB 26; Length 124;
Best Local Similarity 100.0%;
Matches 124; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EVQLVESGGGVVQPGGSLRLSCAASGSTISSYVMGWFRRAPGKEREFVAAISRSGGYTYY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVQLVESGGGVVQPGGSLRLSCAASGSTISSYVMGWFRRAPGKEREFVAAISRSGGYTYY 60
Qy 61 ADSVKGRFTISRDNSKKTAYLQMNSLRPEDTALYYCAAGRYSAWYSQSYEYDYWGQGTLV 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ADSVKGRFTISRDNSKKTAYLQMNSLRPEDTALYYCAAGRYSAWYSQSYEYDYWGQGTLV 120
Qy 121 TVSS 124
||||
Db 121 TVSS 124
WO2019016237 teaches an anti-serum albumin humanized antibody VH region mutant, comprising the amino acid sequence of SEQ:11, which is 86.3% identical to instant SEQ ID NO:18 (see the sequence alignment below).
SEQ ID NO:18
BGB14535
ID BGB14535 standard; protein; 124 AA.
XX
AC BGB14535;
XX
DT 21-MAR-2019 (first entry)
XX
DE Anti-serum albumin VHH humanized antibody VH region mutant, SEQ 11.
XX
KW Albumin; antibody production; heavy chain variale region;
KW humanized antibody; immunoconjugate; mutein.
XX
OS Synthetic.
OS Unidentified.
XX
FH Key Location/Qualifiers
FT Misc-difference 1
FT /note= "Wild type Gln substituted by Glu as a result of
FT humanization"
FT Misc-difference 14
FT /note= "Wild type Ala substituted by Pro as a result of
FT humanization"
FT Misc-difference 75
FT /note= "Wild type Ala substituted by Ser as a result of
FT humanization"
FT Misc-difference 80
FT /note= "Wild type His substituted by Tyr as a result of
FT humanization"
FT Misc-difference 85
FT /note= "Wild type Thr substituted by Ser as a result of
FT humanization"
FT Misc-difference 119
FT /note= "Wild type Gln substituted by Leu as a result of
FT humanization"
XX
CC PN WO2019016237-A1.
XX
CC PD 24-JAN-2019.
XX
CC PF 17-JUL-2018; 2018WO-EP069443.
XX
PR 19-JUL-2017; 2017EP-00182200.
XX
CC PA (VIBV ) VIB VZW.
XX
CC PI Hassanzadeh Ghassabeh G, Schoonooghe S, Depla E;
XX
DR WPI; 2019-09635Y/09.
XX
CC PT New polypeptide comprising immunoglobulin variable domain having
CC PT framework region and complementarity-determining regions and that binds
CC PT to serum albumin used to increase half-life of therapeutic moiety.
XX
CC PS Claim 1; SEQ ID NO 11; 56pp; English.
XX
CC The present invention relates to a novel polypeptide, useful for
CC increasing the half-life of a therapeutic moiety. The polypeptide
CC comprises an immunoglobulin variable region (IVD) specifically binding to
CC a serum albumin, where IVD conjugated to a drug comprises framework
CC regions (FRs) and complementarity determining regions (CDRs). The
CC invention further claims: (1) a therapeutic agent with increased serum
CC half-life, where the therapeutic agent is used as a medicament; (2) a
CC multispecific construct comprising the polypeptide and at least one
CC therapeutic moiety; (3) a nucleotide sequence or nucleic acid encoding
CC the polypeptide; (4) a host cell comprising the polypeptide; (5) a
CC pharmaceutical composition comprising the polypeptide; and (6) a method
CC for producing a serum albumin binding polypeptide preferably antibody.
CC The polypeptide increases the half-life of the therapeutic agent as
CC compared to the half-life of the therapeutic moiety without the
CC polypeptide. The present sequence is an anti-serum albumin single domain
CC antibody (VHH) humanized antibody heavy chain variable region (VH) region
CC mutant, which can be useful for increasing the half-life of a therapeutic
CC moiety in the present invention. Note: SEQ ID NO: 6 is mentioned in
CC example 7 but no corresponding sequence is shown.
XX
SQ Sequence 124 AA;
Query Match 86.3%; Score 560; DB 28; Length 124;
Best Local Similarity 86.3%;
Matches 107; Conservative 3; Mismatches 14; Indels 0; Gaps 0;
Qy 1 EVQLVESGGGLVQAGGSLRLSCAASGSNISSYVMGWFRRAPGKEREFVAAISRSGGYTYY 60
|||| |||||||| |||||||||||| || |||||||:||||||||||||| | | ||
Db 1 EVQLQESGGGLVQPGGSLRLSCAASGRNIKEYVMGWFRQAPGKEREFVAAISWSAGNIYY 60
Qy 61 ADSVKGRFTISRDNAKKTAYLQMNSLEPEDTAVYYCAAGRYSAWYSQSYEYDYWGQGTLV 120
||||||||||||||:| | ||||||| |||||||||||||||||| :||||||||||||
Db 61 ADSVKGRFTISRDNSKNTVYLQMNSLRPEDTAVYYCAAGRYSAWYVAAYEYDYWGQGTLV 120
Qy 121 TVSS 124
||||
Db 121 TVSS 124
17. Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHANG-YU WANG whose telephone number is (571)272-4521. The examiner can normally be reached on Monday-Thursday, 7:00am-5:00pm EST.
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Chang-Yu Wang
September 16, 2026
/CHANG-YU WANG/Primary Examiner, Art Unit 1675
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