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 .
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.
Status of Claims
Claims 2, 5, 9, 11-19, 26, 29-31, 43, 47 and 54-55 are pending. Claims 2, 5, 9, 11-19, 26, 29 and 30 are withdrawn. Claims 31, 43, 47, and 54-55 are under examination.
Withdrawn Rejections
In light of the amendments, the 35 U.S.C. 102(a)(1) rejection over Ware is hereby withdrawn.
Claim Rejections - 35 USC § 112
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 31, 43, 47, 54, 55 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Amended claims 31 and 55 recite limitations of “wherein the transgenic RBC has undergone a treatment to remove one or more native proteins expressed by the transgenic RBC” are unclear to the metes and bounds of the structure of the transgenic RBC which may also be “dissolved” to remove the native proteins. The claim is unclear to what is the structure of the transgenic RBC in the claimed composition after the treatment. Is the transgenic RBC structure intact after the treatment or denatured to remove the native proteins? Meanwhile, if there is the presence of the platelet antigen on the transgenic RBC would it also be removed under the treatment because proteins are being removed; therefore, the platelet antigen is separated or connected to the transgenic RBC? Thus, it is unclear what is in the claimed composition. Claims 43, 47, and 55 are rejected as being dependent from claim 31.
Claim 54 is unclear to the “treatment with proteases under conditions that remove the one or more native proteins but do not remove the alloantigen from the target species”. It is unclear to the structure of the alloantigen because treatment of proteases would denature proteins which is the alloantigen.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 31, 43, 47, 54 and 55 are rejected under 35 U.S.C. 103 as being unpatentable over Ware et al. (“Expression of human Platelet Glycoprotein 1bα in Transgenic Mice”, The Journal of Biological Chemistry, vol. 268, no. 11, Issue of April 15, pgs. 8376-8382, published 1993, see 892 dated 11/20/2025) in view of Bakchoul et al. (“Inhibition of HPA-1a alloantibody-mediated platelet destruction by a deglycosylated anti–HPA-1a monoclonal antibody in mice: toward targeted treatment of fetal-alloimmune thrombocytopenia”, BLOOD, July 18, 2013, vol. 122, no. 3, pgs. 321-327, 892 dated 11/20/2025).
Regarding claims 31 and 54, Ware teaches expression of human glycoprotein (GP)Ibα in transgenic mouse megakaryocytes and found that it was present on the surface of platelets associated with the mouse GPIbβ subunit (see abstract). Ware also teaches in the abstract that the studies demonstrate the transgenic engineering of a platelet adhesion receptor under control. Ware teaches phenotypic analysis of mouse platelets expressing human GP1bα wherein the platelets were detected in whole blood from a mouse (dotted line), a transgenic mouse (solid line) and a human donor (broken line) and incubated with the fluoreinated anti-human GP 1bα monoclonal antibody (see Fig. 1, caption), which would read on a composition that comprising a transgenic red blood cell (i.e., whole blood from transgenic mouse), from a non-target vertebrate animal, that expresses an alloantigen from a target species other than the non-target vertebrate animal (e.g., transgenic mouse) wherein the alloantigen is a platelet antigen (i.e., glycoprotein GP1bα in whole blood of the transgenic mouse) and an antibody bound to the platelet antigen, wherein the antibody is from the target species (i.e., anti-human GP 1bα monoclonal antibody). Ware teaches all mice were tested for platelet surface expression of human GP Ibα with a specific murine monoclonal antibody, LJ-P3; this antibody does not cross-react with the corresponding mouse protein (see pg. 8378, left col., Results and Discussion, para. 2). Note that Fig. 7 of the instant specification discloses that GP1b alpha contains HPA-2a and HPA-2b antigens.
Because Ware teaches expression of human GPIbα antigen (platelet antigen) in transgenic mouse with whole blood that contains transgenic red blood cells, the transgenic mouse containing human GPIbα antigen would read on a composition comprising (open-ended recitation) a transgenic RBC, from a non-target vertebrate animal, that expresses an alloantigen from a target species other than the non-target vertebrate animal, wherein the alloantigen is a platelet antigen. Ware teaches the claimed structure of a general composition that contains transgenic red blood cells (i.e., transgenic whole blood containing transgenic red blood cells). Therefore, Ware’s transgenic mouse either contains platelet antigens expressed on transgenic RBCs or the presence of transgenic RBCs induces the expression of GPIbα antigen on platelets. Either way, Ware’s composition would read on a general structure of a transgenic red blood cell.
However, Ware fails to teach the transgenic RBC has undergone a treatment to remove one or more native proteins expressed by the transgenic RBC, the one or more native proteins being cross-reactive to one or more antibodies from a species other than the non-target vertebrate animal (claim 31) and the treatment comprises glycosidases to remove carbohydrates (claim 54).
Bakchoul teaches human platelet antigen (HPA)-1a and deglycosylation of antibodies abrogates the Fc-related effector functions by endoglycosidase F (abstract). Bakchoul teaches pooling blood samples and assessing the amount of free anti-HPA-1a alloantibodies in the neonatal mouse blood using GPIIIa surface plasmon resonance (SPR) (see pg. 322, right col., para. 3). Bakchoul teaches 2 µL of endo F (see pg. 322, left col., Material and methods, para. 2). Bakchoul teaches the deglycosylated antibody binds via its Fab domain to the HPA-1a epitope on GPIIb-IIIa and lacks key effector functions that promote undesirable Fc-receptor-dependent and the enzymatic digestion was highly effective and specific and seemed not to alter the protein structure of the antibody, as shown by the lack of protein degradation products and, most important, it preserved the binding specificity and affinity of the antibody to its antigen (pg. 325, right col., Discussion, paras. 1-2).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have removed native proteins of the red blood cells as taught by Ware with cleavage as taught by Bakchoul because Bakchoul teaches enzymatic digestion is highly effective to remove undesirable reactions. Therefore, it would have been obvious to have removed undesirable reactions of antibodies for specific detection.
Additionally, it would have been obvious to have used the method of detecting platelet antigens with monoclonal antibody in a transgenic mouse as taught by Ware with glycosidases in solution to remove nonspecific reactions as taught by Bakchoul because Bakchoul teaches enzymatic digestion through deglycosylation is highly effective and specific for antibody detection, as it removes undesirable reactions. Therefore, the person would have used glycosidases to remove undesirable glycan forms that may cross-react with specific antibodies that bind to a GPIbα antigen (glycoprotein containing glycan forms), as recognized in the art that deglycosylation is highly effective to remove undesirable reactions for antibody detection.
The person would have reasonably expected success in deglycosylating glycoproteins of GPIbα antigen in transgenic whole blood samples because it has been well recognized in the art that glycoproteins (antibodies) undergo deglycosylation and whole blood sample contains a wide range of glycoproteins.
With regard to claims 43 and 47, Ware teaches expression of human glycoprotein (GP)Ibα in transgenic mouse megakaryocytes (see abstract). Note that Fig. 7 of the instant specification discloses that GP1b alpha contains HPA-2a and HPA-2b antigens.
With regarding claim 55, the recited steps in the composition are directed to product-by-process. The composition of Ware forms a complex of the platelet antigens in transgenic mouse whole blood (i.e., containing a transgenic RBC) with the monoclonal antibody that is specific for platelet antigens read on the final structure of composition containing a transgenic RBC with the pre-absorbed sample (may or may not include antibody). Note that the claim recites that the sample known or suspected to include antibody is not a positive recitation.
MPEP states that [e]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985) (citations omitted) (Claim was directed to a novolac color developer. The process of making the developer was allowed. The difference between the inventive process and the prior art was the addition of metal oxide and carboxylic acid as separate ingredients instead of adding the more expensive pre-reacted metal carboxylate. The product-by-process claim was rejected because the end product, in both the prior art and the allowed process, ends up containing metal carboxylate. The fact that the metal carboxylate is not directly added, but is instead produced in-situ does not change the end product.). Furthermore, "[b]ecause validity is determined based on the requirements of patentability, a patent is invalid if a product made by the process recited in a product-by-process claim is anticipated by or obvious from prior art products, even if those prior art products are made by different processes." Amgen Inc. v. F. Hoffmann-La Roche Ltd., 580 F.3d 1340, 1370 n 14, 92 USPQ2d 1289, 1312, n 14 (Fed. Cir. 2009). See also Purdue Pharma v. Epic Pharma, 811 F.3d 1345, 117 USPQ2d 1733 (Fed. Cir. 2016). However, in the context of an infringement analysis, a product-by-process claim is only infringed by a product made by the process recited in the claim. Id. at 1370 ("a product in the prior art made by a different process can anticipate a product-by-process claim, but an accused product made by a different process cannot infringe a product-by-process claim"). (see MPEP 2113) (Emphasis added).
Response to Arguments
Applicant's arguments filed 02/20/2026 have been fully considered but they are not persuasive under 35 U.S.C. 112b and 35 U.S.C. 103 rejections.
With respect to the 112b rejection, Applicant argues on pg. 6 that the amendments have overcome the indefiniteness.
The argument is not found persuasive because even though the amendments are currently reciting positive limitations to the claimed invention, it is not clear to the structure of the transgenic red blood cell after the treatment in the composition (see above). Therefore, the rejection has been modified but maintained in view of the indefiniteness rejection above.
With respect to the obviousness rejection, Applicant argues on pg. 7 that Ware teaches platelets from a first species expressing an antigen from a second species. Ware does not disclose a transgenic RBC that expresses an alloantigen from a target species other than the non-target vertebrate.
The arguments are not found persuasive for the following reasons. As stated above, Ware teaches detection in whole blood from a mouse (dotted line), a transgenic mouse (solid line) and a human donor (broken line) and incubated with the fluoreinated anti-human GP 1bα monoclonal antibody (see Fig. 1, caption). Because Ware teaches expression of human GPIbα antigen (platelet antigen) in transgenic mouse with whole blood that contains transgenic red blood cells, the transgenic mouse containing human GPIbα antigen would read on a composition comprising (open-ended recitation) a transgenic RBC. Ware teaches the claimed structure of a general composition that contains transgenic red blood cells (i.e., transgenic whole blood containing transgenic red blood cells). Therefore, Ware’s transgenic mouse either contains platelet antigens expressed on transgenic RBCs or the presence of transgenic RBCs induces the expression of GPIbα antigen on platelets. Either way, Ware’s composition would read on a general structure of a transgenic red blood cell. Meanwhile, there is nothing in the claimed composition that requires the platelet antigen to be expressed on the transgenic RBCs. Also, there is no structural difference between Ware’s transgenic mouse containing a transgenic red blood cell and the claimed transgenic red blood cell before treatment.
Conclusion
No claim is allowed.
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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/N.P.N/Examiner, Art Unit 1678
/SHAFIQUL HAQ/Primary Examiner, Art Unit 1678
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