Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Detailed Action
The Amendments and Remarks filed 4/27/26 in response to the Office Action of 11/25/25 are acknowledged and have been entered.
Claims 1, 5, 12, 15, 47-49, 52, 57, 62, 68, 70, 73, 76, 79, and 81-83 are pending.
Claims 1 and 49 have been amended by Applicant.
Claims 1, 5, 12, 15, 47-49, 52, 57, 62, 68, 70, 73, 76, 79, and 81-83 are currently under examination.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
The following Office Action contains NEW GROUNDS of rejections Necessitated by Amendments.
Rejections Withdrawn
The rejection of claims 49 and 82 under 35 U.S.C. 103(a) as being unpatentable over Liu et al (US 2015/0118216 A1; 4/30/15) in view of Tseng et al (WO 2009/142893 A2; 11/26/09) is withdrawn.
The rejection of claims 1, 12, 47-49, 81, and 82 under 35 U.S.C. 103 as being unpatentable over Liu et al (US 2015/0118216 A1; 4/30/15) in view of Tseng et al (WO 2009/142893 A2; 11/26/09) and Choe et al (Materials, 2016, 9(994): 1-17) is withdrawn.
The rejection of claims 1, 5, 12, 47-49, 73, 76, 79, 81, and 82 under 35 U.S.C. 103 as being unpatentable over Liu et al (US 2015/0118216 A1; 4/30/15) in view of Tseng et al (WO 2009/142893 A2; 11/26/09), Choe et al (Materials, 2016, 9(994): 1-17), Renes et al (British Journal of Pharmacology, 1999, 126: 681-688) and Loe et al (JBC, 1996, 271(16): 9675-9682) is withdrawn.
The rejection of claims 1, 12, 15, 47-49, 81, and 82 under 35 U.S.C. 103 as being unpatentable over Liu et al (US 2015/0118216 A1; 4/30/15) in view of Tseng et al (WO 2009/142893 A2; 11/26/09), Choe et al (Materials, 2016, 9(994): 1-17), and Cortesi et al (New Biotechnology, 2014, 31(1): 44-54) is withdrawn.
Rejections Maintained
Claim Rejections - 35 USC § 103
Claim(s) 52, 57, and 83 remain rejected under 35 U.S.C. 103 as being unpatentable over Liu et al (US 2015/0118216 A1; 4/30/15) in view of Tseng et al (WO 2009/142893 A2; 11/26/09), and Choe et al (Materials, 2016, 9(994): 1-17).
Liu et al teaches delivering proteins, including anionic (negatively charged) proteins, into cells using compositions comprising cationic (positively charged) lipids (same as “cationic transfection agent” carriers), wherein the negatively charged proteins complex with the positively charged lipids and are efficiently delivered into cells ([0004]-[0005], in particular). Liu et al further teaches such delivery can be performed with naturally negatively-charged proteins or with protein fusions/conjugates in which a protein to be delivered is associated with a negatively (or “supernegatively” supercharged) charged protein ([0005], in particular). Liu et al further teaches such delivery wherein the protein to be delivered is a “functional effector protein”, such as an antibody that is fused with a supernegatively charged protein to allow for delivery of the protein into the interior of cells ([0006], in particular). Liu et al further teaches such protein fusions/conjugates comprising the supercharged protein (such as supernegatively charged anionic polypeptide) and the protein to be delivered (such as an antibody) are made by covalently or non-covalently linking, ligating, or fusing the supercharged protein and the protein to be delivered and mixing with cationic (positively charged) lipids (“transfection agent”) ([0005], [0012], and [0014], in particular).
Liu et al teaches making a composition for cytoplasmic delivery by covalently or non-covalently linking, ligating, or fusing the supernegatively (anionic) charged polypeptide 3xFLAG sequence to Cre polypeptide and mixing the conjugate with with cationic RNAiMAX lipids ([0124] and Fig. 33C, in particular). The 23-amino acid 3xFLAG sequence “consists of” MDYKDHDGDYKDHDIDYKDDDDK (SEQ ID NO:48; negatively charged aspartic acid is shown bold and underlined). It is further noted Liu et al further identifies (-30)GFP as a supernegatively/anionic charged proteins that comprise SEQ ID NO: 21 or SEQ ID NO:40 ([0088] and [0166], in particular). At [0119], Liu et al further teaches supernegatively charged polypeptides of composition for cytoplasmic delivery of a protein that are non-covalently linked, ligated, or fused the protein comprise “a sequence of at least 10, at least 20, at least 30, at least 40, at least 50, at least 75, or at least 100 consecutive amino acids.” Liu et al further teaches said delivery wherein the functional effector protein fused or conjugated with the supernegatively charged protein is administered to a subject to therapeutically treat a disease of the subject ([0019] and [0152], in particular).
While Liu et al teaches a supernegatively/anionic charged polypeptide that is 23 amino acids in length and has 11 negatively charged amino acids (SEQ ID NO:48), Liu et al does not specifically teach a supernegatively/anionic charged polypeptide that is “40 amino acid residues or fewer in length and having at least 15 negatively charged amino acids.” Further, Liu et al does not teach not specifically teach conjugates comprising apolyanionic carrier polypeptide and the protein to be delivered (such as an antibody) are made by connecting the polyanionic carrier polypeptide of Tseng et al and the protein to be delivered by linking, ligating, or fusing an antibody binding domain (AbBD) to the polyanionic carrier polypeptide and linking, ligating, or fusing said AbBD to the protein to be delivered (such as antibody). However, these deficiencies are made up in the teachings of Tseng et al and Choe et al.
Tseng et al teaches supernegatively/anionic charged polypeptide used for delivery that comprise 30-100% negatively charged glutamic acid and/or aspartic acid residues (pages 42-43, in particular). Tseng et al further teaches such supernegatively/anionic charged polypeptide include polypeptides that having lengths of about 20, 30, or 40 amino acids (lines 1-5 on page 43, in particular). Tseng et al further teaches such supernegatively/anionic charged polypeptide include polypeptides having various percentages, including 40-100%, of negatively charged glutamic acid and/or aspartic acid residues (last full paragraph on page 42, in particular).
Choe et al demonstrates an Fc-binding protein (including FcBP, a type of AbBD) is capable of linking antibodies to polypeptides (including GFP) for intracellular delivery (Figure 8, in particular). Choe et al further teaches a benefit of using Fc- binding proteins is that the Fc-binding proteins do not interfere with antigen binding of antibodies (page 13, in particular).
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform a combined method of generating and administering the compositions of Liu et al wherein the supernegatively/anionic charged polypeptide is a supernegatively/anionic charged polypeptide having just any length of 20-100 amino acids, as taught by Liu et al, and having 40-100% negatively charged glutamic acid and/or aspartic acid residues, as taught by Tseng et al, because (i) the supernegatively/anionic charged polypeptide of Liu et al is taught to be “a sequence of at least 10, at least 20, at least 30, at least 40, at least 50, at least 75, or at least 100 consecutive amino acids” and used by Liu et al for delivery and (ii) supernegatively/anionic charged polypeptides of Tseng et al include supernegatively/anionic charged polypeptides having lengths of 20-100 amino acids and having 40-100% negatively charged glutamic acid and/or aspartic acid residues used for delivery. Using such a supernegatively/anionic charged polypeptide of Tseng et al in place of a supernegatively/anionic charged polypeptide of Liu et al is an example of a simple substitution of one known element for another to obtain predictable results. Further, the amounts of negatively charged amino acids of the supernegatively/anionic charged polypeptides of Tseng et al predictably render the supernegatively/anionic charged polypeptides of the combined method as supernegative, as envisioned by Liu et al.
Further, the supernegatively/anionic charged polypeptide SEQ ID NO:48 used in compositions of Liu render the superneatively/anionic charged polypeptides of the claims obvious because claimed number of negative amino acids and those of the supernegatively/anionic charged polypeptide SEQ ID NO:48 used in compositions of Liu et al are close. Compositions of Liu et al include a supernegatively/anionic charged polypeptide that is 23 amino acids in length and has 11 negatively charged amino acids (SEQ ID NO:48), while instant claim 52 recites a supernegatively/anionic charged polypeptide that is “40 amino acid residues or fewer in length and having at least 15 negatively charged amino acids.” The 23 amino acids of supernegatively/anionic charged polypeptide (SEQ ID NO:48) of Liu et al are ˃47% negatively charged amino acids, while the claims broadly encompass supernegatively/anionic charged polypeptides that are 37.5-100% negative charge amino acids. MPEP 2144.05 states a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985) (Court held as proper a rejection of a claim directed to an alloy of "having 0.8% nickel, 0.3% molybdenum, up to 0.1% iron, balance titanium" as obvious over a reference disclosing alloys of 0.75% nickel, 0.25% molybdenum, balance titanium and 0.94% nickel, 0.31% molybdenum, balance titanium. "The proportions are so close that prima facie one skilled in the art would have expected them to have the same properties."). See also Warner-Jenkinson Co., Inc. v. Hilton Davis Chemical Co., 520 U.S. 17, 41 USPQ2d 1865 (1997) (under the doctrine of equivalents, a purification process using a pH of 5.0 could infringe a patented purification process requiring a pH of 6.0-9.0); In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%); In re Scherl, 156 F.2d 72, 74-75, 70 USPQ 204, 205-206 (CCPA 1946) (prior art showed an angle in a groove of up to 90° and an applicant claimed an angle of no less than 120°); In re Becket, 88 F.2d 684 (CCPA 1937) ("Where the component elements of alloys are the same, and where they approach so closely the same range of quantities as is here the case, it seems that there ought to be some noticeable difference in the qualities of the respective alloys."); In re Dreyfus, 73 F.2d 931, 934, 24 USPQ 52, 55 (CCPA 1934)(the prior art, which taught about 0.7:1 of alkali to water, renders unpatentable a claim that increased the proportion to at least 1:1 because there was no showing that the claimed proportions were critical); In re Lilienfeld, 67 F.2d 920, 924, 20 USPQ 53, 57 (CCPA 1933)(the prior art teaching an alkali cellulose containing minimal amounts of water, found by the Examiner to be in the 5-8% range, the claims sought to be patented were to an alkali cellulose with varying higher ranges of water (e.g., "not substantially less than 13%," "not substantially below 17%," and "between about 13[%] and 20%"); K-Swiss Inc. v. Glide N Lock GmbH, 567 Fed. App'x 906 (Fed. Cir. 2014)(reversing the Board's decision, in an appeal of an inter partes reexamination proceeding, that certain claims were not prima facie obvious due to non-overlapping ranges); In re Brandt, 886 F.3d 1171, 1177, 126 USPQ2d 1079, 1082 (Fed. Cir. 2018)(the court found a prima facie case of obviousness had been made in a predictable art wherein the claimed range of "less than 6 pounds per cubic feet" and the prior art range of "between 6 lbs./ft3 and 25 lbs./ft3" were so mathematically close that the difference between the claimed ranges was virtually negligible absent any showing of unexpected results or criticality.) In the instant case, absent any showing of unexpected results or criticality, it appears the addition of four more negatively charged amino acids to SEQ ID NO:48 of Liu et al would predictably have the same ability to function as intended by Liu et al.
Further, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method of generating and administering the compositions of the combination of Liu et al and Tseng et al wherein a polyanionic carrier polypeptide of Tseng et al and an antibody to be delivered are connected by linking an Fc-binding protein of Choe et al to the polyanionic carrier polypeptide of Tseng et al and linking said Fc-binding protein of Choe et al to the antibody to be delivered because Liu et al teaches compositions wherein the compositions of a supercharged protein and the protein (including antibody) to be delivered are made by covalently or non-covalently linking the supercharged protein and the protein (including antibody) to be delivered, Choe et al teaches Fc-binding proteins do not interfere with antigen binding of antibodies, and Choe et al demonstrates an Fc- binding protein (including FcBP, a type of AbBD) is capable of covalently or non-covalently linking an antibody to a polypeptide (exemplified with GFP) for intracellular delivery by connecting a polypeptide and an antibody to be delivered by linking an Fc-binding protein of Choe et al to the protein and linking said Fc- binding protein of to the antibody to be delivered (Figure 8, in particular). This is an example of combining prior art elements according to known methods to yield predictable results. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
Response to Arguments
In the Reply of 3/12/26, Applicant argues the polypeptides of Tseng and Choe are not simple substitutions for Liu’s supernegatively charged proteins to obtain predictable results because Liu, Tseng, and Choe use their “polypeptides” differently and each uses a different method of intracellular delivery. Applicant further states that Liu discloses a composition where the “cargo” and supernegatively/anionic charged polypeptides are covalaently liked (as a fusion protein), Tseng disclose a composition where the two components are not attached or fused within cationic lipid complexes – rather the charged polypepties are used to form a network with cationic lipids that trap or enmash the “cargo”. Applicant further states that Choe uses a TAT cell penetrating peptide, and not an anionic polypeptide, for intracellular delivery. Applicant further cites Figure 33C of Liu and argues a skilled artisan would not be motivated with an expectation of success to use a 3xFLAG sequences (SEQ ID NO:48 of Liu) or a sequence “close” to it for delivering an antibody (~150 kDa) because Liu teaches away from doing so by showing 3xFLAG fused to Cre recombinase (~40 kDa) resulted in only ~10% efficacy, as compared to ~65% efficacy with (-30)GFP fused to Cre recombinase. Applicant further cites instant figure 39C and indicates the claimed method is non-obvious because the inventors showed that covalently linking an anionic polypeptide to an antibody is important for successful cytoplasmic delivery of the antibody.
The amendments to the claims and the arguments found in the Reply of 3/12/26 have been carefully considered, but are not deemed persuasive. In regards to the argument that the polypeptides of Tseng and Choe are not simple substitutions for Liu’s supernegatively charged proteins to obtain predictable results because Liu, Tseng, and Choe use their “polypeptides” differently and each uses a different method of intracellular delivery, the rejection does not suggest substituting with polypeptides of Choe. Further, the examiner acknowledges that Liu, Tseng, and Choe use their “polypeptides” differently and each uses a different method of intracellular delivery. However, the examiner maintains one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform a combined method of generating and administering the compositions of Liu et al wherein the supernegatively/anionic charged polypeptide is a supernegatively/anionic charged polypeptide having just any length of 20-100 amino acids, as taught by Liu et al, and having 40-100% negatively charged glutamic acid and/or aspartic acid residues, as taught by Tseng et al, because (i) the supernegatively/anionic charged polypeptide of Liu et al is taught to be “a sequence of at least 10, at least 20, at least 30, at least 40, at least 50, at least 75, or at least 100 consecutive amino acids” and used by Liu et al for delivery and (ii) supernegatively/anionic charged polypeptides of Tseng et al include supernegatively/anionic charged polypeptides having lengths of 20-100 amino acids and having 40-100% negatively charged glutamic acid and/or aspartic acid residues used for delivery.
In regards to the citation of Figure 33C of Liu and argument a skilled artisan would not be motivated with an expectation of success to use a 3xFLAG sequences (SEQ ID NO:48 of Liu) or a sequence “close” to it for delivering an antibody (~150 kDa) because Liu teaches away from doing so by showing 3xFLAG fused to Cre recombinase (~40 kDa) resulted in only ~10% efficacy as compared to ~65% efficacy with (-30)GFP fused to Cre recombinase, the examiner disagrees. Liu et al does not “teach away” from using a 3xFLAG sequences (SEQ ID NO:48 of Liu et al) or a sequence “close” to it for delivering an antibody. Rather, Liu et al teaches 3xFLAG as a supernegatively charged protein associated with a protein to be delivered ([0124], in particular) and specifically teaches a “protein to be delivered” refers to proteins such as antibodies ([0048], in particular). In particular regards to Figure 33C of Liu et al, Liu et al teaches 3xFLAG enhanced functional delivery of Cre recombinase with cationic lipids, though not as effectively as (-30)GFP and indicates that is “likely due to the overall negative charge” and concludes that unusually negatively charged proteins beyond (-30)GFP can mediated efficient cationic lipid-based delivery into mammalian cells ([0316], in particular). Such unusually negatively charged proteins are taught by Tseng et al (pages 42-43, in particular) and include polypeptide similar to 3xFLAG with a more negative charge.
In regards to the citation of instant figure 39C and indication the claimed method is non-obvious because the inventors showed that covalently linking an anionic polypeptide to an antibody is important for successful cytoplasmic delivery of the antibody, the examiner disagrees. Liu et al teaches covalently linking an anionic polypeptide to a protein for cytoplasmic delivery ([0004], in particular) wherein the protein to be delivered is an antibody ([0048], in particular).
Claim Rejections - 35 USC § 103
Claim(s) 52, 57, 62, 68, 70, and 83 remain rejected under 35 U.S.C. 103 as being unpatentable over Liu et al (US 2015/0118216 A1; 4/30/15) in view of Tseng et al (WO 2009/142893 A2; 11/26/09) and Choe et al (Materials, 2016, 9(994): 1-17), as applied to claims 52, 57, and 83 above, and further in view of Renes et al (British Journal of Pharmacology, 1999, 126: 681-688) and Loe et al (JBC, 1996, 271(16): 9675-9682).
Teachings of Liu et al, Tseng et al, and Choe et al are discussed above.
Liu et al, Tseng et al, and Choe et al do not specifically teach administering an IgG or a method of sensitizing a tumor cell to a chemotherapeutic agent comprising administering a conjugate. However, these deficiencies are made up in the teachings of Renes et al and Loe et al.
Renes et al teaches MRP1 is a protein found in multidrug resistant tumor cells and is able to confer resistance to various drugs (including vincristine and daunorubicin) by transporting the drugs (pages 681 and 684, in particular). Renes et al further teaches the anti-MRP1 monoclonal antibody QCRL3 (same as “QCRL-3”) inhibits transport of daunorubicin and vincristine by MRP1 in assays performed with isolated membrane vesicles from multidrug resistant cell lines (Abstract, page left column of 685, and Figure 5, in particular, in particular).
The abstract of Loe et al teaches the QCRL-3 antibody of Renes et al is directed against an intracellular epitope of MRP (same as “MRP1”). Loe et al further teaches QCRL-3 antibody of Renes et al is an IgG (left column on page 9676, in particular).
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform a combined method of treating a subject with tumor cells exhibiting MRP1-mediated multidrug resistance (MDR) to daunorubicin and vincristine comprising generating and administering to said subjects (i) compositions of the combination of Liu et al, Tseng et al, and Choe et al using cationic (positively charged) lipids of Liu et al in which the antibody of the compositions is associated with a polyanionic carrier polypeptide of Tseng et al to be delivered into cells is QCRL-3 antibody of Renes et al followed by (ii) daunorubicin and vincristine administration because Renes et al teaches MRP1 is a protein found in multidrug resistant tumor cells and is able to confer resistance to various drugs, Renes et al teaches the anti-MRP1 antibody QCRL-3 inhibits transport of daunorubicin and vincristine by MRP1 in an MRP1 model using membrane vesicles from multidrug resistant cell lines, Loe et al teaches the QCRL-3 antibody of Renes et al is directed against an intracellular epitope of MRP1, and the compositions using cationic (positively charged) lipids of Liu et al provides a mechanism for intracellular delivery of QCRL-3 in order for QCRL-3 to interact with its binding epitope on MRP1 and sensitize the tumor cells to vincristine and daunorubicin by inhibiting MRP1-mediated transport of vincristine and daunorubicin. This is an example of combining prior art elements according to known methods to yield predictable results.
Regarding claim 79, the Fc-receptor binding protein of Choe et al of the combined method is an AbBD that binds just any Fc domain – including an Fc domain of an anti-RelA IgG antibody. Claim 79 does not require the administered composition to comprise an anti-RelA antibody. Further, while the cited references do not demonstrate the combined method results in inhibiting NF-kB transcription and/or reducing RelA nuclear translocation in a cancer cell, such inhibition and reduction would predictably occur by the combined method because cancer cells killed by the combined method would not predictably transcribe NF-KB and/or exhibit nuclear translocation of RelA. One of skill in the art would recognize vincristine of the combined method kills cancer cells by inducing cell cycle arrest and triggering apoptosis.
Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
Response to Arguments
In the Reply of 4/27/26, Applicant repeats arguments addressed above.
Claim Rejections - 35 USC § 103
Claim(s) 52, 57, and 83 remain rejected under 35 U.S.C. 103 as being unpatentable over Liu et al (US 2015/0118216 A1; 4/30/15) in view of Tseng et al (WO 2009/142893 A2; 11/26/09) and Choe et al (Materials, 2016, 9(994): 1-17), as applied to claims 52, 57, and 83 above, and further in view of Cortesi et al (New Biotechnology, 2014, 31(1): 44-54).
Teachings of Liu et al, Tseng et al, and Choe et al are discussed above.
Liu et al, Tseng et al, and Choe et al do not specifically teach compositions for delivering proteins, including anionic (negatively charged) proteins, into cells using compositions comprising cationic (positively charged) lipid carriers wherein the cationic lipids are described as cationic lipid “nano-carriers”. However, these deficiencies are made up in the teachings of Cortesi et al.
Cortesi et al teaches cationic lipid nano-carriers as cationic lipids used to deliver DNA into cells (Abstract, in particular).
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to generate and administer the compositions of Liu et al, Tseng et al, and Choe et al comprising cationic (positively charged) lipid carriers for delivering proteins, including anionic (negatively charged) proteins, into cells wherein the cationic lipids are just any cationic lipids, including “nano-carrier” cationic lipids of Cortesi et al because one of skill in the art would recognize anionic proteins and cationic lipid nano-carriers would form complexes due to opposing charges and Liu et al teaches anionic protein : cationic lipid complexes are efficiently delivered into cells ([0005], in particular). Substituting the cationic lipid nano-carriers in place of the cationic lipid carriers of the compositions of Liu et al, Tseng et al, and Choe et al is an example of a simple substitution of one known element for another to obtain predictable results. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
Response to Arguments
In the Reply of 4/27/26, Applicant repeats arguments addressed above.
New Rejections Necessitated by Amendments
Claim Rejections - 35 USC § 112
Claim 49 is 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.
Claim 49 is rejected because step “(ii)” of the claim recites “…covalently crosslinking the to an Fab region or an Fc region of an antibody….” There appears to be a term, such as “AbBD”, missing between “the” and “to”. The metes-and-bounds of the claim are unclear because it is unclear what is to be crosslinked to an Fab or Fc region.
Claim Rejections - 35 USC § 103
Claim(s) 1, 12, 47-49, 81, and 82 are rejected under 35 U.S.C. 103 as being unpatentable over Liu et al (US 2015/0118216 A1; 4/30/15) in view of Tseng et al (WO 2009/142893 A2; 11/26/09) and Choe et al (Materials, 2016, 9(994): 1-17) as applied to claims 52, 57, and 83 above, and further in view of Tsourkas et al (WO 2016/183387 A1; 11/17/16; 5/15/21 IDS).
Teachings of Liu et al, Tseng et al, and Choe et al are discussed above.
Liu et al, Tseng et al, and Choe et al do not specifically teach whether the Fc binding protein of the combined method connecting the antibody to the polyanionic carrier polypeptide is “covalently crosslinked” to the Fc domain of the antibody. However, these deficiencies are made up in the teachings of Tsourkas et al.
Tsourkas et al teaches covalently crosslinking a polypeptide bound to an Fc domain of an antibody prevents dissociation of the polypeptide from the antibody upon administration (lines 16-17 on page 30, in particular).
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method wherein the Fc binding protein of the combined method connecting the antibody to the polyanionic carrier polypeptide is “covalently crosslinked” to the Fc domain of the antibody because Tsourkas et al teaches covalently crosslinking a polypeptide bound to an Fc domain of an antibody prevents dissociation of the polypeptide from the antibody upon administration (lines 16-17 on page 30, in particular). This is an example of some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to combine prior art reference teachings to arrive at the claimed invention. See MPEP 2143. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
Claim Rejections - 35 USC § 103
Claim(s) 1, 5, 12, 47-49, 73, 76, 79, 81, and 82 is/are rejected under 35 U.S.C. 103 as being unpatentable over Liu et al (US 2015/0118216 A1; 4/30/15) in view of Tseng et al (WO 2009/142893 A2; 11/26/09), Choe et al (Materials, 2016, 9(994): 1-17), Renes et al (British Journal of Pharmacology, 1999, 126: 681-688) and Loe et al (JBC, 1996, 271(16): 9675-9682) as applied to claims 52, 57, 62, 68, 70, and 83 above, and further in view of Tsourkas et al (WO 2016/183387 A1; 11/17/16; 5/15/21 IDS).
Teachings of Liu et al, Tseng et al, Choe et al, Renes et al, and Loe et al are discussed above.
Liu et al, Tseng et al, Choe et al, Renes et al, and Loe et al do not specifically teach whether the Fc binding protein of the combined method connecting the antibody to the polyanionic carrier polypeptide is “covalently crosslinked” to the Fc domain of the antibody. However, these deficiencies are made up in the teachings of Tsourkas et al.
Tsourkas et al teaches covalently crosslinking a polypeptide bound to an Fc domain of an antibody prevents dissociation of the polypeptide from the antibody upon administration (lines 16-17 on page 30, in particular).
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method wherein the Fc binding protein of the combined method connecting the antibody to the polyanionic carrier polypeptide is “covalently crosslinked” to the Fc domain of the antibody because Tsourkas et al teaches covalently crosslinking a polypeptide bound to an Fc domain of an antibody prevents dissociation of the polypeptide from the antibody upon administration (lines 16-17 on page 30, in particular). This is an example of some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to combine prior art reference teachings to arrive at the claimed invention. See MPEP 2143. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
Claim Rejections - 35 USC § 103
Claim(s) 1, 12, 15, 47-49, 81, and 82 is/are rejected under 35 U.S.C. 103 as being unpatentable over Liu et al (US 2015/0118216 A1; 4/30/15) in view of Tseng et al (WO 2009/142893 A2; 11/26/09), Choe et al (Materials, 2016, 9(994): 1-17), and Cortesi et al (New Biotechnology, 2014, 31(1): 44-54) as applied to claims 52, 57, and 83 above, and further in view of Tsourkas et al (WO 2016/183387 A1; 11/17/16; 5/15/21 IDS).
Liu et al, Tseng et al, Choe et al, and Cortesi et al are discussed above.
Liu et al, Tseng et al, Choe et al, and Cortesi et al do not specifically teach whether the Fc binding protein of the combined method connecting the antibody to the polyanionic carrier polypeptide is “covalently crosslinked” to the Fc domain of the antibody. However, these deficiencies are made up in the teachings of Tsourkas et al.
Tsourkas et al teaches covalently crosslinking a polypeptide bound to an Fc domain of an antibody prevents dissociation of the polypeptide from the antibody upon administration (lines 16-17 on page 30, in particular).
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method wherein the Fc binding protein of the combined method connecting the antibody to the polyanionic carrier polypeptide is “covalently crosslinked” to the Fc domain of the antibody because Tsourkas et al teaches covalently crosslinking a polypeptide bound to an Fc domain of an antibody prevents dissociation of the polypeptide from the antibody upon administration (lines 16-17 on page 30, in particular). This is an example of some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to combine prior art reference teachings to arrive at the claimed invention. See MPEP 2143. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/SEAN E AEDER/ Primary Examiner, Art Unit 1642
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