Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
DETAILED ACTION
Pursuant to a preliminary amendment filed January 5, 2024, claims 38-110 are currently pending in the instant application.
Response to Election/Restriction
Applicant's election of Group I, claims 46-53 directed to a method for separating antibodies or fusion polypeptides; and Applicant’s election of Species as follows:
Species (A): wherein the non-covalent complex of soluble human FcRn extracellular domain (SEQ ID NO: 7) with a C-terminal His-Avi Tag (SEQ ID NO: 8) and human b-2-microglobulin (SEQ ID NO: 9) (claim 46),
Species (B): wherein the neonatal Fc receptor and the b-2-microglobulin are each independently of human origin (claim 47), and
Species (C): wherein the positive linear pH gradient is from a first pH value to a second pH value, wherein the first pH value is about from about pH 3.5 to about pH 7.5…to about pH 9.5 (claim 51), in the reply filed September 24, 2026 is acknowledged.
Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election of invention has been treated as an election without traverse (MPEP
§ 818.03(a)).
Claims 38-45 and 54-110 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected invention, there being no allowable generic or linking claim.
Claim 52 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected species, there being no allowable generic or linking claim.
The restriction requirement is still deemed proper and is therefore made FINAL.
The claims will be examined insofar as they read on the elected species.
Therefore, claims 46-51 and 53 are under consideration to which the following grounds of rejection are applicable.
Information Disclosure Statement
The information disclosure statements (IDSs) submitted on November 9, 2023; June 4, 2024 and August 19, 2025 have been considered. An initialed copy of the IDSs accompany this Office Action.
Priority
The present application filed August 17, 2023 is a CON of US Patent Application 16258294 (now US11814409), which is a CON of US Patent Application 14378808, filed August 14, 2014, which is a 35 U.S.C. 371 national stage filing of International Application PCT/EP2013/052932, filed February 14, 2013, which claims the benefit of European Patent Application EP12155630.02, filed February 15, 2012.
Claim Objections/Rejections
Claim Objection
Claim 46 is objected to because of the following informalities: Claim 46 recites the terms “Fc-region” and "FcRn” in lines 1-2, where an abbreviation should be spelled out in the first encounter of the claims.
Appropriate correction is required.
Claim Rejections - 35 USC § 112, 2nd paragraph
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 46-51 and 53 are rejected under 35 U.S.C. 112, 2nd paragraph as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention.
Claims 46-51 and 53 are indefinite because none of the claims positively recite any steps of a method for separating antibodies or fusion polypeptides. Instant claims 46-51 and 53 recite various structural features of a non-covalent complex, but the claims do not recite any positive steps for separating antibodies and/or fusion polypeptides and, thus, the metes and bounds of the claims cannot be determined.
Claim 48 is indefinite for the recitation of the term “the same species” such as recited in claim 48, lines 1-2. There is insufficient antecedent basis for the term “the same species” in the claim. Moreover, claim 48 depends from instant claim 46, wherein claim 46 does not recite that the b-2-microglobulin (B2M) and Fc receptor are obtained from a species and, thus, the metes and bounds of the claim cannot be determined.
Claim 49 is indefinite for the recitation of the term “0 to 10 amino acid residue modifications” such as recited in claim 49, line 3 because claim 49 depends from instant claim 46, wherein claim 46 does not recite that the Fc receptor and the b-2-microglobulin (B2M) comprise modifications and, thus, the metes and bounds of the claim cannot be determined.
Claim 50 is indefinite for the recitation of the term “bound to a solid phase” such as recited in claim 50, line 2 because claim 50 depends from instant claim 46, wherein claim 46 recites that the non-covalent complex comprises neonatal Fc receptor and B2M, but it does not recite that the complex comprises a solid phase and, thus, the metes and bounds of the claim cannot be determined.
Claim 53 is indefinite for the recitation of the terms “the antibody”, “a mono-specific antibody”, “antibody fragment of fusion polypeptide”, “a bispecific antibody”, “a trispecific antibody”, and/or “a tetraspecific antibody” such as recited in claim 53, lines 1-4. There is insufficient antecedent basis for the terms “the antibody”, “a mono-specific antibody”, “antibody fragment of fusion polypeptide”, “a bispecific antibody”, “a trispecific antibody”, and/or “a tetraspecific antibody” in the claim because claim 1, line 1 recites the term “antibodies”.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 48-50 are rejected under 35 U.S.C. 112(d) as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 48 recites (in part): “wherein b-2-microglobulin is from the same species as the neonatal Fc receptor” such as recited in claim 48, lines 1-2 because claim 48 depends from instant claim 46, wherein claim 46 does not recite that the b-2-microglobulin (B2M) and Fc receptor are obtained from a species and/or synthetically produced. Thus, claim 48 is an improper dependent claim for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 49 recites (in part): “wherein the neonatal Fc receptor and the b -2-microglobulin are the human wild-type neonatal Fc receptor and the human wild type b -2-microglobulin…0 to 10 amino acid residue modifications” such as recited in claim 49, lines 1-4 because claim 49 depends from instant claim 46, wherein claim 46 does not recite that the non-covalent complex comprising b-2-microglobulin (B2M) and the Fc receptor comprise amino acid residue modifications and/or indicate how the components were obtained. Thus, claim 49 is an improper dependent claim for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 50 recites (in part): “wherein the non-covalent complex of a neonatal Fc receptor and b -2-microglobulin is bound to a solid phase” such as recited in claim 50, lines 1-2 because claim 50 depends from instant claim 46, wherein claim 46 does not recite that the non-covalent complex comprises a solid phase. Thus, claim 50 is an improper dependent claim for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Applicant may cancel the claim, amend the claim to place the claim in proper dependent form, rewrite the claim in independent form, or present a sufficient showing that the dependent claim complies with the statutory requirements.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negated by the manner in which the invention was made.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
This application currently names joint inventors. In considering patentability of the claims under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 46-51 and 53 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over McDonnell et al. (hereinafter “MacDonnell”) (US Patent Application Publication 20120021484, published January 26, 2012; effective filing date October 22, 2008) in view of Johansson et al. (hereinafter “Johansson”) (US Patent Application Publication 20120149875, published June 14, 2012; effective filing date January 12, 2009).
Regarding claim 46, McDonnell teaches methods of purifying Fc-containing molecules using a soluble neonatal Fc receptor (sFcRn), wherein native FcRn binds Fc-containing proteins at or below about pH 6.5 and releases them at or above about pH 7 and provides a much milder approach for capturing and purifying Fc-containing proteins, such as therapeutic Fc-containing proteins; as well as, modifications to alter the pH for binding and elution to the sFcRn, to modulate Fc-containing protein binding affinity, to affect sFcRn linkage to a support surface, or to improve the stability of sFcRn to conditions utilized in the methods of the invention (interpreted as a method of separating antibodies or fusion polypeptides comprising an Fc-region; an affinity column; neonatal Fc receptor; and interpreting “native” to mean wild-type, claim 46) (Abstract). McDonnell teaches that FcRn consists of a heavy chain (a-chain) non-covalently bound to a light chain b-2-microglobulin (B2M) (interpreted as non-covalent complex with B2M, claim 1) (paragraph [0007], lines 1-4). McDonnell teaches a method of purifying an Fc-containing protein using an sFcRn linked to a support surface wherein one or both heavy chain (a-chain) or light chain (B2M) domains are modified to modulate Fc-containing protein binding, such as a higher affinity interaction could lead to a more efficient purification of dilute samples of Fc-containing proteins of interest, wherein the modification encompasses a mutation or mutations to one or both the a-chain or B2M of sFcRn including mutations that either increase or decrease the binding affinity of Fc-containing proteins to sFcRn; a mutation or mutations to one or both the a-chain or B2M of sFcRn that either increases or decreases the binding affinity of Factor VIII:Fc to sFcRn; and/or a mutation or mutations to one or both the a-chain or B2M of sFcRn including mutations that either increase or decrease the optimal pH for ligand binding and/or release (interpreting purifying as separating antibodies or fusion polypeptides comprising an Fc-region; and residue modifications that increase or decrease optimal pH for binding and/or release, claim 46) (paragraph [0012]). McDonnell teaches a method of purifying an Fc-containing protein using an sFcRn linked to a support surface wherein the sFcRn a-chain or B2M are modified to improve the stability of the sFcRn to conditions required for multiple cycles of use (interpreted as an affinity column; and bound to a solid phase, claims 46 and 50) (paragraph [0014], lines 1-5). McDonnell teaches that the column was washed with pH 6.0 buffer and the bound Factor VIII:Fc was released by eluting the column with pH 7.5 buffer (interpreted as a positive gradient; eluting encompassing a linear pH gradient; and a first pH from 3.5-7.5 and a second pH from 6-9, claims 46 and 51) (paragraph [0019], lines 8-11). McDonnell teaches purifying an Fc-containing protein using sFcRn linked to a support surface comprising binding an Fc-containing protein to the sFcRn-linked surface at or below about pH 7.0 and the step of eluting said Fc-containing protein at or above about pH 7.0, respectively (interpreted as a positive gradient, claim 46) (paragraph [0050]). McDonnell teaches that alternative embodiments of the method are envisioned where FcRn variants are used which bind and elute Fc-containing proteins at pH levels other than about 7.0 such as, for example, pH levels of at or below about 7.0 to about 4.0 can be used to bind Fc-containing proteins, and pH levels of at or above about 7.0 to about 10.0 can be used to elute Fc-containing proteins (interpreted as encompassing a positive linear gradient; and a first pH from 3.5-7.5 and a second pH from 6-9, claim 46) (paragraph [0050], lines 10-16).
Regarding claim 47, McDonnell teaches that antibodies and other Fc fusion proteins bind to Fc receptors (FcR) through the Fc region, such as the Fc region of an IgG, wherein Figure 1 shows an SDS-PAGE comparison of samples from a capture and release of Fc fragment using a soluble human FcRn (interpreted as human origin, claim 47) (paragraphs [0005], lines 1-3; [0016], lines 1-3; and Figure 1). McDonnell teaches that the term “Fc region” refers to the C-terminal region of a human IgG heavy chain (interpreted as Fc receptor is of human origin, claim 47) (paragraph [0032], lines 1-4).
Regarding claims 48 and 49, McDonnell teaches that the FcR is a native sequence human FcR (interpreted as wild-type human FcR, claim 49) (paragraph [0041], lines 4-6). McDonnell teaches that native sequence human Fc regions include a native sequence human IgG1 Fc region; native sequence human IgG2 Fc region; native sequence human IgG3 Fc region; and native sequence human IgG4 regions, as well as, naturally occurring variants thereof (interpreted as modifications encompassing
0-10 amino acid modifications, claim 49) (paragraphs [0040]). McDonnell teaches that “sFcRn” includes native and variant a-chain and B2M polypeptides (interpreted as native human FcR and B2M; same species; and encompassing 0-10 amino acid modifications, claims 48 and 49) (paragraph [0042]). McDonnell teaches that the term "variant" (or analog) refers to a polypeptide differing from a specifically recited polypeptide of the invention, such as FcRn, by amino acid insertions, deletions, and substitutions, created using, e.g., recombinant DNA techniques, such as mutagenesis, such that guidance in determining which amino acid residues can be replaced, added, or deleted without abolishing activities of interest, can be found by comparing the sequence of the particular polypeptide with that of homologous peptides, e.g., human, primate, mouse, rat, bovine, porcine FcRn (interpreted as modifications encompassing 0 to 10 residue modifications, claim 49) (paragraph [0035]).
Regarding claim 50, McDonnell teaches a method of purifying an Fc-containing protein using an sFcRn linked to a support surface wherein the sFcRn a-chain or B2M are modified to improve the stability of the sFcRn to conditions required for multiple cycles of use (interpreted as an affinity column; and bound to a solid phase, claims 46 and 50) (paragraph [0014], lines 1-5). McDonnell teaches that the column was washed with pH 6.0 buffer and the bound Factor VIII:Fc was released by eluting the column with pH 7.5 buffer (interpreting binding a column as a being bound to a solid phase, claim 50) (paragraph [0019], lines 8-11).
Regarding claim 51, McDonnell teaches purifying an Fc-containing protein using sFcRn linked to a support surface comprising binding an Fc-containing protein to the sFcRn-linked surface at or below about pH 7.0 and the step of eluting said Fc-containing protein at or above about pH 7.0, respectively (interpreted as a positive gradient, claim 51) (paragraph [0050], lines 1-9). McDonnell teaches that alternative embodiments of the method are envisioned where FcRn variants are used which bind and elute Fc-containing proteins at pH levels other than about 7.0 such as, for example, pH levels of at or below about 7.0 to about 4.0 can be used to bind Fc-containing proteins, and pH levels of at or above about 7.0 to about 10.0 can be used to elute Fc-containing proteins (interpreted as a positive gradient; and a first pH from 3.5-7.5 and a second pH from 6-9, claim 51) (paragraph [0050], lines 10-16).
Regarding claim 53, McDonnell teaches that the term "Fc-containing protein" is intended to include antibodies and Fc fusion proteins, wherein antibodies include whole antibody molecules, including monoclonal, polyclonal, and multi-specific (e.g., bispecific) antibodies, as well as antibody fragments having the Fc region and retaining binding specificity and at least one effector function, and single chain antibodies, single chain Fv molecules, Fab fragments, diabodies, triabodies, tetrabodies, and the like (interpreted as antibodies and/or fusion proteins as recited, claim 53) (paragraph [0031], lines 1-9).
McDonnell does not specifically exemplify a linear pH gradient (claim 51, in part)
Regarding claim 51 (in part), Johansson teaches a method of separating one or more immunoglobulin containing proteins from a liquid including first contacting the liquid with a separation matrix comprising ligands immobilized to a support; allowing the immunoglobulin containing proteins to adsorb to the matrix by interaction with the ligands; followed by an optional step of washing the adsorbed immunoglobulin containing proteins; and recovering said immunoglobulin containing proteins by contacting the matrix with an eluent which releases the proteins (interpreted as separating antibodies, etc.; FcR affinity column; and a non-covalent ligand, claim 46) (Abstract). Johansson teaches that the term "Fc fragment-binding" protein means that the protein is capable of binding to the Fc fragment of an immunoglobulin; however, it is not excluded that an Fc fragment-binding protein also can bind other regions, such as Fab regions of immunoglobulins (paragraph [0020]). Johansson teaches a method of separating one or more immunoglobulin containing proteins from a liquid, which method comprises (a) contacting the liquid with a separation matrix comprising ligands immobilized to a support; (b) allowing the immunoglobulin containing proteins to adsorb to the matrix by interaction with the ligands; (c) an optional step of washing the adsorbed immunoglobulin containing proteins; and (d) recovering the immunoglobulin containing proteins by contacting the matrix with an eluent which releases the proteins, wherein the method provides increased binding capacity of the ligands to the immunoglobulin molecules by using a monomeric ligand, such as domain B of staphylococcal Protein A (SpA) or protein Z (paragraph [0023]). Johansson teaches in Example 4, investigating the elution of several monoclonal antibodies purified on different z-ligands on agarose-based matrix, wherein elution was performed in a linear pH gradient (interpreted as a linear pH gradient, claim 51) (paragraph [0136], lines 1-4).
It is prima facie obvious to combine prior art elements according to known methods to yield predictable results; the court held that, "…a conclusion that a claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded nothing more than predictable results to one of ordinary skill in the art. KSR International Co. v. Teleflex Inc., 550 U.S. ___, ___, 82 USPQ2d 1385, 1395 (2007); Sakraida v. AG Pro, Inc., 425 U.S. 273, 282, 189 USPQ 449, 453 (1976); Anderson’s-Black Rock, Inc. v. Pavement Salvage Co., 396 U.S. 57, 62-63, 163 USPQ 673, 675 (1969); Great Atlantic & P. Tea Co. v. Supermarket Equipment Corp., 340 U.S. 147, 152, 87 USPQ 303, 306 (1950)”. Therefore, in view of the benefits of purifying antibodies on different ligands on a matrix as exemplified by Johansson, it would have been prima facie obvious for one of ordinary skill in the art at the time the invention was made to modify the method of purifying Fc-containing proteins using sFcRn, which is non-covalently bound to b-2-microglobulin, and linked to a solid support that is eluted with a pH gradient, wherein modifications to the sFcRn and/or B2M cause an increase or decrease in binding affinity and/or in the optimal pH for ligand binding and/or release of an Fc-containing protein and/or an Fc fragment as disclosed by McDonnell to include the linear pH gradient as taught by Johansson with a reasonable expectation of success in efficiently purifying Fc-containing proteins and/or fragments using affinity chromatography at a pH below about 7.0 to about 4.0 to a pH of above about 7.0 to 10.0; in determining what mutations in one or both a-chains of B2M of sFcRn increase or decrease binding affinity of Fc-containing proteins to sFcRn; and/or in determining the optimal pH for the binding or release or Fc-containing proteins of interest.
Thus, in view of the foregoing, the claimed invention, as a whole, would have been obvious to one of ordinary skill in the art at the time the invention was made. Therefore, the claims are properly
rejected under 35 USC §103(a) as obvious over the art.
Conclusion
Claims 46-51 and 53 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMY M BUNKER whose telephone number is (313) 446-4833. The examiner can normally be reached on Monday-Friday (6am-2:30pm).
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.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Heather Calamita can be reached on (571) 272-2876. The fax phone number for the organization where this application or proceeding is assigned is (571) 273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/AMY M BUNKER/
Primary Examiner, Art Unit 1684
Prosecution Insights